Toxicology and Forensic Medicine – Open Journal (e-ISSN 2474-8978) is an open access peer-reviewed journal that publishes subjects related to toxicology and forensic medicine.
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Background
Snakebite is a collective health problem that afflicts areas with poor healthcare cov... more Background Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology. Aims In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice. Results For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables. Conclusion In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.
Background
Theophylline poisoning leads to multisystem toxicity. Management of theophylline overd... more Background Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose. Case Presentation A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced. Conclusion Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.
Background
Environmental toxicants have become a major source of health hazards to humans, there... more Background Environmental toxicants have become a major source of health hazards to humans, thereby negatively impacting the health and overall well-being of exposed individuals. Among these environmental toxicants, heavy metals stand out as the major cause of tissue pathologies and threaten an individual’s health status. One such heavy metal is cadmium (CD) whose exposure has been linked to various tissue toxicities including nervous, respiratory, reproductive, cardiovascular, hepatic and renal tissues. Cadmium is a non-biodegradable heavy metallic which possesses a long half of lifestyles and comfortably accumulates inside the tissues in which it produces tissue toxicities main to tissue disorder. The present study was aimed to determine the amelioration capabilities of Vitamin C, E and Zinc from the harmful effects of CD in Wistar rats. Methods The Wistar strain male albino rats weighing 225±10 g were administered with CD along co-administered with Vitamin C, E and Zinc, individually and also in combinations. After the completion of 45-days of experimentation, certain specific enzymatic parameters were assayed in plasma serum to assess the impact of CD and protective effect of Vitamin C, E and Zinc. Results Soon after the co-administration of CD along with Vitamin C, E and Zinc, either individually and in combinations, Body weights, liver weight and histo-somatic index (HSI) of liver and certain specific enzymes of plasma including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, glucose and urea were monitored. All the parameters monitored showed a significant (p< 0.05) increase during CD administration except ALP. All the parameters selected in the present study were shown to be significantly (p< 0.05) reversed due to co-administration of Vitamin C, E and Zinc either individually or in combination, due to the protective effect from CD toxicity in wistar rats. Conclusion Our results demonstrate that co-administration of Vitamin C, E and Zinc ably protects the toxicity of CD in Wistar rats significantly.
Neurological disorders are a ubiquitous part of our lives, and with innovative technological adva... more Neurological disorders are a ubiquitous part of our lives, and with innovative technological advancements there are increasing numbers of people being diagnosed with a variety of conditions. While these advances uncover the underlying pathological process, the requisite need to manage a patient’s condition necessitates renewed vigour in the realm of key therapeutics. This case study looks at a patient with a rare neurological condition, transverse myelitis (TM), and a complication that many spinal cord injury patients suffer, autonomic dysreflexia (AD). However, what makes this case unique is when the patient was administered with immediate-release Tapentadol, a synthetic opioid, the patient suffered more frequent and prolonged attacks of AD. The exploration of the functional anatomy of TM as it applies to this case is highlighted, and how the role of Tapentadol was a causative agent in increasing the patient’s AD.
Aim
The present study investigated the effects of cypermethrin exposure on humoral and cellular ... more Aim The present study investigated the effects of cypermethrin exposure on humoral and cellular immune response in rat and its attenuation by zinc and alpha-lipoic acid. Methods Cypermethrin at the dose levels of 40 mg and 80 mg/kg body weight were orally administered and pre-treatment of zinc (227 mg/L in drinking water) and alpha-lipoic acid (35 mg/kg body wt.) were done. Total leukocyte and differential leukocyte counts (DLC), phagocytic index, serum nitric oxide (NO) activity, total immunoglobulin concentration, quantitative hemolysis, proliferation assay of blood mononuclear cells were estimated and histological examination of spleen was accomplished. Results Total white blood cell (WBC) count and percentage of lymphocyte, serum nitric oxide activity (p<0.001) and quantitative hemolysis were increased significantly increased whereas neutrophil %, total serum immunoglobulin, and blood mononuclear cell proliferation (p<0.001) and the phagocytic function of peritoneal macrophages were significantly reduced in cypermethrin treated rats compared to control group rats at a dose-dependent manner. Zinc and alpha-lipoic acid pre-treatment reversed the results. Conclusion From the findings it can be concluded that the co-administration of zinc and alpha-lipoic acid significantly attenuated the immunotoxic effects in cypermethrin exposed rat.
Introduction
Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, b... more Introduction Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial. Aim Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication. Method The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading. Results Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007). Conclusion This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.
Carbon monoxide (CO) is a toxic gas produced as a result of incomplete combustion of organic mate... more Carbon monoxide (CO) is a toxic gas produced as a result of incomplete combustion of organic materials. The source of CO production is very common especially in nations that depend on power generating sets for electricity. Chronic disease is non-communicable and usually takes a longer time to manifest. Examples are kidney failure, diabetes mellitus, hypertension, cancer, and cardiac arrest. These diseases are now very common in society, not sparing the youthful population that was rare ab initio. The major difficulty in the containment of chronic diseases is the inability to establish a definitive causative agent. The definite causative agent is important in public health and management of chronic diseases. Preventive medicine is anchored on establishing the causative agent of a disease. Without knowing the causative agent of a disease, the path to prevention becomes very cumbersome. The knowledge of the causative agent of a disease is the bedrock of preventive medicine and public health. Several reasons such as lifestyle modification, hereditary, climate change, nutrition or aging have been adduced as the cause of chronic diseases. These reasons are quite weak and not definite. The exact causative agent(s) of chronic diseases is a conundrum that needs a deliberate study and review so as to enhance definite diagnosis, preventive measures and appropriate therapeutic intervention. Measurement of biochemical and haematological parameters are employed in disease diagnosis and management. Alterations of these parameters are used to identify chronic diseases and also form part of an alarm system of a potential breakdown of the normal functioning of the body. The effect of chronic CO intoxication on these parameters could be of importance in establishing causative agent(s) of diseases that are for long opaque and non-definite. This review was therefore designed to interrogate various narratives, meta-analysis, and researches on this subject. Explicit knowledge of the pattern or presentation of biochemical and haematological parameters arising from chronic CO intoxication could be of great importance in preventive medicine, disease diagnosis and appropriate therapeutic intervention.
Background
Decontamination is a critical medical counter measure in reducing toxic exposure follo... more Background Decontamination is a critical medical counter measure in reducing toxic exposure following poisoning. Little is known on the effectiveness of this procedure and its impact in the context of preventing secondary exposure of healthcare workers and secondary contamination of facilities. Presented here is a case of dimethoate poisoning that required a prolonged period of skin decontamination to remove residual skin contamination. Case Report A young gardener consumed dimethoate at the workplace witnessed by a colleague who called the emergency services immediately. Paramedics noted the patient to be drowsy with stable vital signs and 100% oxygen saturation. En-route to the hospital the patient vomited multiple times and was drenched in vomitus with a pungent odour. Upon arrival at the emergency department (ED), vital signs remained stable with a Glasgow Coma Scale (GCS) of 10. Due to gross external contamination from the vomitus and pungent odours emanating suggestive of chemical fumes off-gassing, the hospital decontamination shower was activated for patient decontamination. Staff donned protective suits and proceeded to disrobe and bag all the patient’s clothing before showering the patient for 10-minutes using soap and water. Post-decontamination a chemical agent monitor (CAM) were used to screen for residual chemicals following the hospital’s decontamination protocol. The chemical alarm was triggered twice, first around the left mastoid region and again just below the left breast. This required targeted re-showering for a further 10-minutes before patient was finally cleared of contamination. Subsequently, the patient was given atropine (2.4 mg) and pralidoxime (1 g) followed by an infusion at the intensive care unit (ICU). The patient made an uneventful recovery and was discharged 5-days later. Conclusion This case of dimethoate poisoning is notable for the prolonged period of skin decontamination to remove residual skin contamination and illustrates potential implications to patient and health care worker safety. Past mass casualty incidents involving chemicals, such as the sarin attack in Tokyo, highlight the high incidence of secondary exposures amongst healthcare workers due to the lack of casualty decontamination. As a result, many hospitals have developed capacity to conduct rapid and timely decontamination at their premises to prevent further complications from secondary chemical exposure. However, the effectiveness of this process of decontamination needs further evaluation.
Aim
A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix fo... more Aim A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix for monitoring prescription and illicit drugs in a clinical setting on patients undergoing pain and addiction treatment. The current standard for monitoring patients’ medication use, misuse, and diversion is urine drug testing (UDT). Materials and Methods This study compared 632 paired urine and fingerstick blood specimens collected at three pain management clinics and one suboxone clinic for 35 drugs and/or metabolites. Plasma from the fingerstick blood was used for the analysis. The urine and plasma specimens were analyzed by validated liquid chromatography–tandem mass spectrometry (LC-MS-MS) procedures. The urine cutoff used by most pain testing laboratories were used to identify positive and negative drugs in urine. Limit of quantitation was used to identify positive and negative drugs in plasma. Drugs and/or metabolites were quantified in both urine and plasma using deuterium-labeled internal standards. Results Results were tabulated for urine and plasma specimens for data analysis. The results showed that 8.7% of plasma specimens detected more drugs compared to the corresponding urine specimens, and 2.2% of the urine specimens detected a drug that was negative in the corresponding plasma specimen. Overall 89.1% of the specimens had complete agreement between urine and plasma specimens for detection. The observed Cohen’s Kappa value for overall drug detection was 0.96 an “almost perfect” agreement as characterized by Landis and Koch. Conclusion Based on the observed data, the authors conclude that plasma collected from fingerstick blood is a better matrix to monitor patients currently prescribed pain medications or patients currently undergoing medication-assisted opioid treatment compared to urine drug testing.
Statins are widely used in the management or inhibition of several processes that lead to the dev... more Statins are widely used in the management or inhibition of several processes that lead to the development of cardiovascular diseases. Increased statin therapy has been related to the induction of type II diabetes (DM), a state which predisposes to cardiovascular disease (CVD). Statins are well-known to possess anti-inflammatory properties and the ability to disrupt de novo biosynthesis of cholesterol and lipid homeostasis has been implicated in the induction of inflammatory responses within pancreatic β-cells. Inhibition of β-hydroxy β-methyl glutaryl-CoA (HMG-CoA) results an increased level of low-density lipoproteins (LDL) receptors. Increased LDL receptor numbers will replenish exhausted intracellular supplies, resulting in higher levels of intracellular cholesterol. Therefore, stimulating immunological response and inflammatory reactions, disrupt the functional integrity of the β-cell via oxidation of the plasma-derived low-density lipoprotein. Despite the pleiotropic effects of statins on the pancreatic β-cell, they have also been reported to affect a number of other cell types associated with the development of diabetes. Inhibition of the biosynthesis of isoprenoid by statins has been associated with the down-stream regulation of glucose transporter (GLUT 4) in adipose tissues, which facilitates the uptake of glucose. This effect resulted in increasing resistance to insulin in the liver, muscle, and adipose tissue. Adiponectin, a plasma protein released by adipocytes, alters fatty acids and carbohydrate metabolism both in the muscle cells and liver. This process indirectly influences resistance to insulin by the attendant decrease in hepatic gluconeogenesis and to upregulate muscular β-oxidation and glucose uptake.
Since the Sarin incident in the subways of Tokyo in 1995, there has been an unprecedented increas... more Since the Sarin incident in the subways of Tokyo in 1995, there has been an unprecedented increase in the use of chemical agents on civilian populations internationally. This scourge of chemical terrorism has been relentless worldwide and is likely to continue to be a public health issue that needs to be addressed by the relevant authorities as part of national disaster preparedness and response. One aspect of chemical disasters involves the need for mass decontamination of chemically-contaminated casualties from the scene. The traditional role of hazardous materials civil defence experts in providing such decontamination of victims in the pre-hospital setting is limited by many factors. The presence of congestion in densely populated areas in a highly built up environment of modern-day cities, compounds the timeliness of putting up cordons and crowd control and hence delays the prompt set up of such mobile decontamination facilities close to the incident site. The expected side effect is an almost instantaneous influx of contaminated casualties to the nearest hospital in such situations, which drives the need for public hospitals to be ultimately capable of performing mass casualty decontamination as part of hazardous materials disaster preparedness. This review presents an innovatively designed rapidly deployable hospital-based decontamination facility that has served a tertiary care hospital in Singapore for the last 2 decades in being prepared for managing mass casualties arriving from a chemical disaster in a timely manner.
Most individuals first think of insects when they hear the word ‘entomology,’ yet entomology is a... more Most individuals first think of insects when they hear the word ‘entomology,’ yet entomology is a much broader topic involved with the study of multiple organisms such as millipedes, centipedes, arachnids and other insects as well as crustaceans (collectively referred to as arthropods). The forensic application is how these organisms can be used in legal investigations. Most often, forensic entomology deals with feeding insects which aid in determining the time of death, but there is more information that can be collected from the action of insects on dead and decaying flesh. Subsets of the forensic entomology field can be subdivided into three subsets: urban, stored product and medico-legal.1 The beginnings of forensic entomology can be traced back to the 1200’s in China, with Sung Tzu as the ‘first’forensic entomologist. Other notable forensic entomologists have been Francesco Redi (1600’s), Bergert d’Arbois (1800’s) and Hermann Reinhard (late 1800’s). Key advancements in forensic entomology have only happened over the last 150 years. A significant amount of work has been submitted by Reinhard and Hofmann in the late 1800’s in Germany and France, respectively.2 Initially, arthropods were valued for their ability to assist in determining the postmortem interval. Later, arthropod use became valuable in determining the cause of death due to the presence of drugs or poisoning.2 The ability of arthropods to help define the time of death is astounding.3,4 Conventional measurements such as body temperature and rigor are only accurate for a couple of days and are significantly altered due to differences in ambient temperature. The growth cycle of the blowfly (the larvae phase being maggots) is highly consistent, and as one of the first inhabitants of a cadaver, the stage of blowfly development can be back calculated to determine with a high level of accuracy, time of death.2,5,6 The site where the death occurred has an enormous impact on the types of arthropod infestations which would be specific to the location of the cadaver and various arthropods have been examined based on their specificity in gauging time, and place of death.7-11 In addition to arthropods, the use of fungi has also been utilized to aid in determining postmortem interval and location of death.12 In the last decade, concerted efforts have been made to establish uniform guidelines for the practice of forensic entomology and define a series of best practices that can be utilized by any laboratory.13
Aims
An intricate relationship exists between the mitochondrial function and proteasome activity.... more Aims An intricate relationship exists between the mitochondrial function and proteasome activity. Our recent report showed in a rat model of renal transplantation that mitochondrial dysfunction precedes compromised proteasome function and this results in a vicious cycle of mitochondrial injury and proteasome dysfunction. In this study, we studied whether reactive oxygen species (ROS) has a role in proteasome alteration in renal cells and vice versa. Methods We used the genomic and pharmacologic approach on rat normal kidney proximal tubular (NRK) cell lines. First, we knocked down β5 or Rpt6 subunit of the proteasome using small interfering RNA (siRNA) in NRK cells. We also treated NRK cells with Bortezomib, a proteasome inhibitor, and peroxynitrite (a potent ROS). Results Studies with RNA interference showed increased mitochondrial ROS following knockdown of β5 or Rpt6 subunit in NRK cells. Similarly, pharmacological inhibition of the proteasome in NRK cells using Bortezomib also showed an increase of mitochondrial ROS in a dose-dependent manner. Next, exposing NRK cells to different concentrations of peroxynitrite provided evidence that the higher levels of peroxynitrite exposure decreased the key subunits (β5 and α3) of the proteasome in NRK cells. Conclusion Our results suggest that proteasome inhibition/downregulation increases ROS, which then impairs proteasome subunits in renal proximal tubular cells.
The Drug and Poison Information Center (DPIC) in Singapore was run as a pilot project over 4 year... more The Drug and Poison Information Center (DPIC) in Singapore was run as a pilot project over 4 years from April 2004 to March 2008. The center provided a hotline service for toxic exposure assessment and management to healthcare professionals and the general public. The aim of this study was to review poisonings through the perspective of this poison center. Method A retrospective review of records in the DPIC call database was made covering the 4 years of its operation. Drug information and adverse effects calls were excluded from the study. Results There was a total of 15227 calls to the DPIC over the study period. Of these, 1817 calls (11.9%) were on acute toxic exposures involving patients. Healthcare personnel working in public restructured hospitals were the most frequent users (71.4%) of the service with the majority of these calls originating from the emergency departments (86%). Public inquiries accounted for 16.6% of the call volume. The cohort of poisoning cases showed a bimodal distribution of age groups with peaks in the less than 5 age group and the 20 to 40 year age group. The racial distribution followed local population demographics but with almost equal gender representation (50.3%males). Most exposures were accidental (67.4%) and occurred at home (69%). The number of agents involved in each exposure ranged from one (84.5%) to a maximum of 6 (<1%) agents. The common exposures involved analgesics (13.5%), antidepressants and sedatives (10.6%), industrial chemicals (5.7%) and bites and stings (8.4%). The calls were evenly distributed by month of the year with no significant seasonal variation although the daily distribution showed a peak in the late evening. The DPIC was able to complete immediate definitive advice within 15 minutes of the call in most situations (96.5%). Majority of public calls (69.2%) ended with reassurance and advice to observe for relevant symptoms. A similar disposition was observed even when the calls were from physicians. Conclusion In summary, poisonings were mostly accidental and affected the younger population suggesting that they are potentially preventable. Furthermore, the DPIC appears to have played a significant triaging role in toxic exposures; providing reassurance for minor poisoning cases while facilitating the appropriate referral of the more severe ones.
Background
Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoi... more Background Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoisomeric pairs of cyhalothrin, containing an alpha-cyano group. Taurine or 2-aminoethane sulfonic acid is a sulfur-containing α-amino acid that is the most abundant free amino acid in most mammal tissue. Aim and Objectives The present study was focused to investigate lambda-cyhalothrin induced nephrotoxicity and renal oxidative stress as well as to evaluate the alleviating role of taurine in this condition. Methods Lambda-cyhalothrin was administered orally at two dose levels (10.83 and 15.17 mg/kg body weight) alone or in combination after pre-treatment of taurine (50 mg/kg body weight) for consecutive 14 days. Results Renal toxicity was measured by a significant decrease in renal index, reduction in kidney protein and an increase in serum protein in lambda-cyhalothrin intoxicated rats. At the same time, lambda-cyhalothrin induced a significant renal oxidative stress demonstrated by elevated renal malondialdehyde content and oxidized glutathione level accompanied by a reduction in reduced glutathione and antioxidant enzymes in rats. Lambda-cyhalothrin induced renal toxicity and oxidative stress in the rat was significantly ameliorated due to the administration of taurine as an antidote. Conclusion All of these findings of the present study strongly suggest the protective role of taurine in the pathophysiology of lambda-cyhalothrin-induced renal toxicity and oxidative stress.
Homocysteine (HCY) is a non-protein sulfur-containing amino acid. It has received a great deal of... more Homocysteine (HCY) is a non-protein sulfur-containing amino acid. It has received a great deal of attention over the last two decades within the scientific community for its unique role in the induction of several diseases ranging from atherosclerotic cardiovascular disease to neural tube defects (NTD). The hypothesis that hyperhomocysteinemia (HHCY) causes atherosclerosis was proposed by McCully1 in 1969, when he observed that children with homocysteinuria had atherosclerotic plaques of the peripheral, coronary, and cerebral vasculature. In 1976, the initial epidemiological study of Wilcken and Wilcken 2 supported this hypothesis and provided the first evidence of the pathogenic role of HCY in atherosclerotic cardiovascular disease and alcoholism. HCY strictly associated with alcohol consumption and enhanced the alcohol consumption that leads to alcohol-related disorders such as brain atrophy, epileptic seizures during withdrawal, and mood disorders.3 Although, HHCY involves both genetic and nutritional causes,4 the mechanism of HCY toxicity is not completely understood.
Background: Pesticides are used frequently and may have various adverse effects on human health i... more Background: Pesticides are used frequently and may have various adverse effects on human health in different ways. Cypermethrin (CYP) is a synthetic type II pyrethroid pesticide that has been used extensively to control a wide variety of pests in agriculture, forestry, horticulture, and public health. Objectives: This study aimed to investigate the dose-dependent hematological, hepatic and gonadal toxicity of CYP in mature male and female Wistar rats. Methods: Rats were randomly divided into nine groups, different doses of CYP were administered for 14 consecutive days and different hematological, hepatic and gonadal parameters were assayed. Results: Erythrocyte count, hemoglobin percentage, hepatic reduced glutathione (GSH) content and sperm count were significantly diminished. Serum aspartic and alanine transaminase, hepatic malondialdehyde (MDA), testicular cholesterol content were increased following CYP treatment in male rats at 40 and 80 mg/kg body weight (1/9 and 1/4.5 LD 50). Elevated ovarian cholesterol content and decreased 17β hydroxy steroid dehydrogenase (HSD) levels were also observed in CYP-exposed female rats at a dose level of 34.33 and 51.5 mg/kg body wt. (1/9 and 1/6 LD 50). Conclusion: Taken together, CYP initiated hematological, hepatic and gonadal toxicity in mature male rats with a body weight of 40 mg/kg (1/9 LD 50) and gonadal toxicity in mature female rats with a body weight of 34.33 mg/kg (1/9 LD 50) and above.
Background: Pollution of aquatic ecosystems with heavy metals leads to decrease of the biodiversi... more Background: Pollution of aquatic ecosystems with heavy metals leads to decrease of the biodiversity and accumulation of toxicants in the food chain. Species of the genus Scenedesmus are sensitive indicators of environmental changes and have been used for the evaluation of risk factors for contamination of aquatic ecosystems. The microalga Scenedesmus incrassatulus can remove chromium and cadmium from the growth medium. Also, mammalian cell lines are another type of test system that has been used to study the mechanisms of heavy metal toxicity. However, little is known about the sensitivity and potential application of different human cell lines for bio-monitoring of heavy metal contamination. Aim: To investigate the toxicity of increasing concentrations of cadmium, nickel and lead on the green microalga Scenedesmus incrassatulus and the human cell lines HeLa, A549, FL, and Caco-2. Materials and Methods: To evaluate the toxic effects of Cd, Ni, and Pb, two test systems were used: an algal culture of S. incrassatulus and four human cell lines. For the algal system, the growth of the algae and the features such as "cell number in the coenobium/single cells", "po-sition of the inner cells in the coenobium", and "shape of the peripheral cell", were assessed. For the human cell cultures, the methyl-thiazol-tetrazolium (MTT) and neutral red assays were performed. In both the systems, the effects were measured at different time points (24, 48, and 72 hours) of treatment. Results: The experimental observations showed that lead exposure in maximal permissible levels (MPL) inhibited the growth of the green algae S. incrassatulus, while cadmium had a stimulating effect even at lower test concentrations. Cadmium and nickel treatment affected the morphological features "cell number in the coenobium/single cells" and "position of the inner cells in the coenobium". Regarding "shape of the peripheral cell", lead had the most significant effect after 24 h of treatment, which was expressed in reduction of the type "incrassatulus" compared to the type "obliquus". Cytotoxic effects of the heavy metals were also observed for all tested human cell lines. HeLa, FL and Caco-2 were most sensitive to cadmium compared to lead, while A549 cells showed equal sensitivity to all three heavy metals. Conclusion: The reported data presented specific impacts on the studied parameters for both the test-systems. The present study concluded that the green alga S. incrassatulus could be used as an effective test system for the biomonitoring of lead pollution. The cell line A549 can serve as a sensitive test system for the presence of cadmium, nickel and lead.
Aim: To determine the interaction of over-the-counter (OTC) and illicit psychostimulants at the c... more Aim: To determine the interaction of over-the-counter (OTC) and illicit psychostimulants at the cytochrome P450 enzyme, CYP2D6. CYP2D6 is responsible for 20% of hepatic Phase I metabolism and is a site of drug drug interactions, leading to increased drug toxicity. Materials and Methods: We examined the effects the OTC drugs; 1) the prototype H2-antagonist cimetidine (CMT) and 2) the opioid agonist cough suppressant dextromethorphan (DEX); as well as two scheduled drugs, methamphetamine (MA) and 3,4 methylenedioxymethamphetamine (MDMA) for their ability to interfere with CYP2D6 activity. Assays with human CYP2D6 determined the inhibitory potential (IC50) of each drug. Kinetic analysis (Vmax and Km) was accomplished using rodent hepatic microsomes. Results: Maximum inhibition of CYP2D6 activity following exposure to CMT+MDMA was significantly reduced 75-85% compared to quinidine (control) values. These data showed inhibitory effects in CYP2D6 activity in each compound tested. Alterations in CYP2D6 activity may result in complex drug-drug interactions leading to elevated plasma levels of drugs and increased risk for toxicity. Assays using rat CYP2D2 demonstrated Vmax elevations in the CMT group (493%) compared to control (naïve, no treatment) values (19.9±5.1 pmol/mg protein/min). The Km was increased 218% in CMT compared to controls (3.1±0.5 μM). Collectively, all MA challenged groups exhibited increases in total enzyme [Vmax; 280-490%] and affinity [Km; 165-220%] values compared to the control group. The increase in both Vmax and Km suggests that the low affinity/high capacity CYP2D2 isoform is upregulated. Conclusion: Our findings suggest that in vivo, MA acts as a CYP2D2-inducer, which will lead to altered secondary drug metabolism, increasing the risk of drug-related toxicity. Coupled with the ability of CMT and DEX to interfere with MA metabolism, a complex drug-drug interaction is possible, leading to increased toxicity. Our findings substantiate the hypothesis that the combination of illicit and OTC drugs could result in complex drug-drug interactions increasing the risk for severe drug-related toxicity.
Background: Human identification requires the maintenance of population databases of short tandem... more Background: Human identification requires the maintenance of population databases of short tandem repeat (STR) loci that allow for their correct interpretation during paternity testing and forensic cases. Material and Methods: We analyzed 15 STR loci with the AmpFlSTR ® Identifiler kit in a Mestizo (admixed) population sample from the state of Guerrero (South Mexico). Results: We estimated the allele distribution and different forensic parameters in this population. Genotype distribution was in agreement with the Hardy-Weinberg expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated no association between the pair of loci. The power of exclusion and power of discrimination values were 99.9994% and >99.99999%, respectively. Interpopulation analysis suggested that the Mestizo populations from the Central and the Southern regions conform one population cluster, separated from the Southeastern and Northwestern regions. Conclusions: We describe the genetic structure of Mexican Mestizos based on 15 STRs reporting for the first time a population representing the Southern region.
Background
Snakebite is a collective health problem that afflicts areas with poor healthcare cov... more Background Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology. Aims In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice. Results For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables. Conclusion In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.
Background
Theophylline poisoning leads to multisystem toxicity. Management of theophylline overd... more Background Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose. Case Presentation A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced. Conclusion Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.
Background
Environmental toxicants have become a major source of health hazards to humans, there... more Background Environmental toxicants have become a major source of health hazards to humans, thereby negatively impacting the health and overall well-being of exposed individuals. Among these environmental toxicants, heavy metals stand out as the major cause of tissue pathologies and threaten an individual’s health status. One such heavy metal is cadmium (CD) whose exposure has been linked to various tissue toxicities including nervous, respiratory, reproductive, cardiovascular, hepatic and renal tissues. Cadmium is a non-biodegradable heavy metallic which possesses a long half of lifestyles and comfortably accumulates inside the tissues in which it produces tissue toxicities main to tissue disorder. The present study was aimed to determine the amelioration capabilities of Vitamin C, E and Zinc from the harmful effects of CD in Wistar rats. Methods The Wistar strain male albino rats weighing 225±10 g were administered with CD along co-administered with Vitamin C, E and Zinc, individually and also in combinations. After the completion of 45-days of experimentation, certain specific enzymatic parameters were assayed in plasma serum to assess the impact of CD and protective effect of Vitamin C, E and Zinc. Results Soon after the co-administration of CD along with Vitamin C, E and Zinc, either individually and in combinations, Body weights, liver weight and histo-somatic index (HSI) of liver and certain specific enzymes of plasma including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, glucose and urea were monitored. All the parameters monitored showed a significant (p< 0.05) increase during CD administration except ALP. All the parameters selected in the present study were shown to be significantly (p< 0.05) reversed due to co-administration of Vitamin C, E and Zinc either individually or in combination, due to the protective effect from CD toxicity in wistar rats. Conclusion Our results demonstrate that co-administration of Vitamin C, E and Zinc ably protects the toxicity of CD in Wistar rats significantly.
Neurological disorders are a ubiquitous part of our lives, and with innovative technological adva... more Neurological disorders are a ubiquitous part of our lives, and with innovative technological advancements there are increasing numbers of people being diagnosed with a variety of conditions. While these advances uncover the underlying pathological process, the requisite need to manage a patient’s condition necessitates renewed vigour in the realm of key therapeutics. This case study looks at a patient with a rare neurological condition, transverse myelitis (TM), and a complication that many spinal cord injury patients suffer, autonomic dysreflexia (AD). However, what makes this case unique is when the patient was administered with immediate-release Tapentadol, a synthetic opioid, the patient suffered more frequent and prolonged attacks of AD. The exploration of the functional anatomy of TM as it applies to this case is highlighted, and how the role of Tapentadol was a causative agent in increasing the patient’s AD.
Aim
The present study investigated the effects of cypermethrin exposure on humoral and cellular ... more Aim The present study investigated the effects of cypermethrin exposure on humoral and cellular immune response in rat and its attenuation by zinc and alpha-lipoic acid. Methods Cypermethrin at the dose levels of 40 mg and 80 mg/kg body weight were orally administered and pre-treatment of zinc (227 mg/L in drinking water) and alpha-lipoic acid (35 mg/kg body wt.) were done. Total leukocyte and differential leukocyte counts (DLC), phagocytic index, serum nitric oxide (NO) activity, total immunoglobulin concentration, quantitative hemolysis, proliferation assay of blood mononuclear cells were estimated and histological examination of spleen was accomplished. Results Total white blood cell (WBC) count and percentage of lymphocyte, serum nitric oxide activity (p<0.001) and quantitative hemolysis were increased significantly increased whereas neutrophil %, total serum immunoglobulin, and blood mononuclear cell proliferation (p<0.001) and the phagocytic function of peritoneal macrophages were significantly reduced in cypermethrin treated rats compared to control group rats at a dose-dependent manner. Zinc and alpha-lipoic acid pre-treatment reversed the results. Conclusion From the findings it can be concluded that the co-administration of zinc and alpha-lipoic acid significantly attenuated the immunotoxic effects in cypermethrin exposed rat.
Introduction
Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, b... more Introduction Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial. Aim Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication. Method The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading. Results Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007). Conclusion This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.
Carbon monoxide (CO) is a toxic gas produced as a result of incomplete combustion of organic mate... more Carbon monoxide (CO) is a toxic gas produced as a result of incomplete combustion of organic materials. The source of CO production is very common especially in nations that depend on power generating sets for electricity. Chronic disease is non-communicable and usually takes a longer time to manifest. Examples are kidney failure, diabetes mellitus, hypertension, cancer, and cardiac arrest. These diseases are now very common in society, not sparing the youthful population that was rare ab initio. The major difficulty in the containment of chronic diseases is the inability to establish a definitive causative agent. The definite causative agent is important in public health and management of chronic diseases. Preventive medicine is anchored on establishing the causative agent of a disease. Without knowing the causative agent of a disease, the path to prevention becomes very cumbersome. The knowledge of the causative agent of a disease is the bedrock of preventive medicine and public health. Several reasons such as lifestyle modification, hereditary, climate change, nutrition or aging have been adduced as the cause of chronic diseases. These reasons are quite weak and not definite. The exact causative agent(s) of chronic diseases is a conundrum that needs a deliberate study and review so as to enhance definite diagnosis, preventive measures and appropriate therapeutic intervention. Measurement of biochemical and haematological parameters are employed in disease diagnosis and management. Alterations of these parameters are used to identify chronic diseases and also form part of an alarm system of a potential breakdown of the normal functioning of the body. The effect of chronic CO intoxication on these parameters could be of importance in establishing causative agent(s) of diseases that are for long opaque and non-definite. This review was therefore designed to interrogate various narratives, meta-analysis, and researches on this subject. Explicit knowledge of the pattern or presentation of biochemical and haematological parameters arising from chronic CO intoxication could be of great importance in preventive medicine, disease diagnosis and appropriate therapeutic intervention.
Background
Decontamination is a critical medical counter measure in reducing toxic exposure follo... more Background Decontamination is a critical medical counter measure in reducing toxic exposure following poisoning. Little is known on the effectiveness of this procedure and its impact in the context of preventing secondary exposure of healthcare workers and secondary contamination of facilities. Presented here is a case of dimethoate poisoning that required a prolonged period of skin decontamination to remove residual skin contamination. Case Report A young gardener consumed dimethoate at the workplace witnessed by a colleague who called the emergency services immediately. Paramedics noted the patient to be drowsy with stable vital signs and 100% oxygen saturation. En-route to the hospital the patient vomited multiple times and was drenched in vomitus with a pungent odour. Upon arrival at the emergency department (ED), vital signs remained stable with a Glasgow Coma Scale (GCS) of 10. Due to gross external contamination from the vomitus and pungent odours emanating suggestive of chemical fumes off-gassing, the hospital decontamination shower was activated for patient decontamination. Staff donned protective suits and proceeded to disrobe and bag all the patient’s clothing before showering the patient for 10-minutes using soap and water. Post-decontamination a chemical agent monitor (CAM) were used to screen for residual chemicals following the hospital’s decontamination protocol. The chemical alarm was triggered twice, first around the left mastoid region and again just below the left breast. This required targeted re-showering for a further 10-minutes before patient was finally cleared of contamination. Subsequently, the patient was given atropine (2.4 mg) and pralidoxime (1 g) followed by an infusion at the intensive care unit (ICU). The patient made an uneventful recovery and was discharged 5-days later. Conclusion This case of dimethoate poisoning is notable for the prolonged period of skin decontamination to remove residual skin contamination and illustrates potential implications to patient and health care worker safety. Past mass casualty incidents involving chemicals, such as the sarin attack in Tokyo, highlight the high incidence of secondary exposures amongst healthcare workers due to the lack of casualty decontamination. As a result, many hospitals have developed capacity to conduct rapid and timely decontamination at their premises to prevent further complications from secondary chemical exposure. However, the effectiveness of this process of decontamination needs further evaluation.
Aim
A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix fo... more Aim A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix for monitoring prescription and illicit drugs in a clinical setting on patients undergoing pain and addiction treatment. The current standard for monitoring patients’ medication use, misuse, and diversion is urine drug testing (UDT). Materials and Methods This study compared 632 paired urine and fingerstick blood specimens collected at three pain management clinics and one suboxone clinic for 35 drugs and/or metabolites. Plasma from the fingerstick blood was used for the analysis. The urine and plasma specimens were analyzed by validated liquid chromatography–tandem mass spectrometry (LC-MS-MS) procedures. The urine cutoff used by most pain testing laboratories were used to identify positive and negative drugs in urine. Limit of quantitation was used to identify positive and negative drugs in plasma. Drugs and/or metabolites were quantified in both urine and plasma using deuterium-labeled internal standards. Results Results were tabulated for urine and plasma specimens for data analysis. The results showed that 8.7% of plasma specimens detected more drugs compared to the corresponding urine specimens, and 2.2% of the urine specimens detected a drug that was negative in the corresponding plasma specimen. Overall 89.1% of the specimens had complete agreement between urine and plasma specimens for detection. The observed Cohen’s Kappa value for overall drug detection was 0.96 an “almost perfect” agreement as characterized by Landis and Koch. Conclusion Based on the observed data, the authors conclude that plasma collected from fingerstick blood is a better matrix to monitor patients currently prescribed pain medications or patients currently undergoing medication-assisted opioid treatment compared to urine drug testing.
Statins are widely used in the management or inhibition of several processes that lead to the dev... more Statins are widely used in the management or inhibition of several processes that lead to the development of cardiovascular diseases. Increased statin therapy has been related to the induction of type II diabetes (DM), a state which predisposes to cardiovascular disease (CVD). Statins are well-known to possess anti-inflammatory properties and the ability to disrupt de novo biosynthesis of cholesterol and lipid homeostasis has been implicated in the induction of inflammatory responses within pancreatic β-cells. Inhibition of β-hydroxy β-methyl glutaryl-CoA (HMG-CoA) results an increased level of low-density lipoproteins (LDL) receptors. Increased LDL receptor numbers will replenish exhausted intracellular supplies, resulting in higher levels of intracellular cholesterol. Therefore, stimulating immunological response and inflammatory reactions, disrupt the functional integrity of the β-cell via oxidation of the plasma-derived low-density lipoprotein. Despite the pleiotropic effects of statins on the pancreatic β-cell, they have also been reported to affect a number of other cell types associated with the development of diabetes. Inhibition of the biosynthesis of isoprenoid by statins has been associated with the down-stream regulation of glucose transporter (GLUT 4) in adipose tissues, which facilitates the uptake of glucose. This effect resulted in increasing resistance to insulin in the liver, muscle, and adipose tissue. Adiponectin, a plasma protein released by adipocytes, alters fatty acids and carbohydrate metabolism both in the muscle cells and liver. This process indirectly influences resistance to insulin by the attendant decrease in hepatic gluconeogenesis and to upregulate muscular β-oxidation and glucose uptake.
Since the Sarin incident in the subways of Tokyo in 1995, there has been an unprecedented increas... more Since the Sarin incident in the subways of Tokyo in 1995, there has been an unprecedented increase in the use of chemical agents on civilian populations internationally. This scourge of chemical terrorism has been relentless worldwide and is likely to continue to be a public health issue that needs to be addressed by the relevant authorities as part of national disaster preparedness and response. One aspect of chemical disasters involves the need for mass decontamination of chemically-contaminated casualties from the scene. The traditional role of hazardous materials civil defence experts in providing such decontamination of victims in the pre-hospital setting is limited by many factors. The presence of congestion in densely populated areas in a highly built up environment of modern-day cities, compounds the timeliness of putting up cordons and crowd control and hence delays the prompt set up of such mobile decontamination facilities close to the incident site. The expected side effect is an almost instantaneous influx of contaminated casualties to the nearest hospital in such situations, which drives the need for public hospitals to be ultimately capable of performing mass casualty decontamination as part of hazardous materials disaster preparedness. This review presents an innovatively designed rapidly deployable hospital-based decontamination facility that has served a tertiary care hospital in Singapore for the last 2 decades in being prepared for managing mass casualties arriving from a chemical disaster in a timely manner.
Most individuals first think of insects when they hear the word ‘entomology,’ yet entomology is a... more Most individuals first think of insects when they hear the word ‘entomology,’ yet entomology is a much broader topic involved with the study of multiple organisms such as millipedes, centipedes, arachnids and other insects as well as crustaceans (collectively referred to as arthropods). The forensic application is how these organisms can be used in legal investigations. Most often, forensic entomology deals with feeding insects which aid in determining the time of death, but there is more information that can be collected from the action of insects on dead and decaying flesh. Subsets of the forensic entomology field can be subdivided into three subsets: urban, stored product and medico-legal.1 The beginnings of forensic entomology can be traced back to the 1200’s in China, with Sung Tzu as the ‘first’forensic entomologist. Other notable forensic entomologists have been Francesco Redi (1600’s), Bergert d’Arbois (1800’s) and Hermann Reinhard (late 1800’s). Key advancements in forensic entomology have only happened over the last 150 years. A significant amount of work has been submitted by Reinhard and Hofmann in the late 1800’s in Germany and France, respectively.2 Initially, arthropods were valued for their ability to assist in determining the postmortem interval. Later, arthropod use became valuable in determining the cause of death due to the presence of drugs or poisoning.2 The ability of arthropods to help define the time of death is astounding.3,4 Conventional measurements such as body temperature and rigor are only accurate for a couple of days and are significantly altered due to differences in ambient temperature. The growth cycle of the blowfly (the larvae phase being maggots) is highly consistent, and as one of the first inhabitants of a cadaver, the stage of blowfly development can be back calculated to determine with a high level of accuracy, time of death.2,5,6 The site where the death occurred has an enormous impact on the types of arthropod infestations which would be specific to the location of the cadaver and various arthropods have been examined based on their specificity in gauging time, and place of death.7-11 In addition to arthropods, the use of fungi has also been utilized to aid in determining postmortem interval and location of death.12 In the last decade, concerted efforts have been made to establish uniform guidelines for the practice of forensic entomology and define a series of best practices that can be utilized by any laboratory.13
Aims
An intricate relationship exists between the mitochondrial function and proteasome activity.... more Aims An intricate relationship exists between the mitochondrial function and proteasome activity. Our recent report showed in a rat model of renal transplantation that mitochondrial dysfunction precedes compromised proteasome function and this results in a vicious cycle of mitochondrial injury and proteasome dysfunction. In this study, we studied whether reactive oxygen species (ROS) has a role in proteasome alteration in renal cells and vice versa. Methods We used the genomic and pharmacologic approach on rat normal kidney proximal tubular (NRK) cell lines. First, we knocked down β5 or Rpt6 subunit of the proteasome using small interfering RNA (siRNA) in NRK cells. We also treated NRK cells with Bortezomib, a proteasome inhibitor, and peroxynitrite (a potent ROS). Results Studies with RNA interference showed increased mitochondrial ROS following knockdown of β5 or Rpt6 subunit in NRK cells. Similarly, pharmacological inhibition of the proteasome in NRK cells using Bortezomib also showed an increase of mitochondrial ROS in a dose-dependent manner. Next, exposing NRK cells to different concentrations of peroxynitrite provided evidence that the higher levels of peroxynitrite exposure decreased the key subunits (β5 and α3) of the proteasome in NRK cells. Conclusion Our results suggest that proteasome inhibition/downregulation increases ROS, which then impairs proteasome subunits in renal proximal tubular cells.
The Drug and Poison Information Center (DPIC) in Singapore was run as a pilot project over 4 year... more The Drug and Poison Information Center (DPIC) in Singapore was run as a pilot project over 4 years from April 2004 to March 2008. The center provided a hotline service for toxic exposure assessment and management to healthcare professionals and the general public. The aim of this study was to review poisonings through the perspective of this poison center. Method A retrospective review of records in the DPIC call database was made covering the 4 years of its operation. Drug information and adverse effects calls were excluded from the study. Results There was a total of 15227 calls to the DPIC over the study period. Of these, 1817 calls (11.9%) were on acute toxic exposures involving patients. Healthcare personnel working in public restructured hospitals were the most frequent users (71.4%) of the service with the majority of these calls originating from the emergency departments (86%). Public inquiries accounted for 16.6% of the call volume. The cohort of poisoning cases showed a bimodal distribution of age groups with peaks in the less than 5 age group and the 20 to 40 year age group. The racial distribution followed local population demographics but with almost equal gender representation (50.3%males). Most exposures were accidental (67.4%) and occurred at home (69%). The number of agents involved in each exposure ranged from one (84.5%) to a maximum of 6 (<1%) agents. The common exposures involved analgesics (13.5%), antidepressants and sedatives (10.6%), industrial chemicals (5.7%) and bites and stings (8.4%). The calls were evenly distributed by month of the year with no significant seasonal variation although the daily distribution showed a peak in the late evening. The DPIC was able to complete immediate definitive advice within 15 minutes of the call in most situations (96.5%). Majority of public calls (69.2%) ended with reassurance and advice to observe for relevant symptoms. A similar disposition was observed even when the calls were from physicians. Conclusion In summary, poisonings were mostly accidental and affected the younger population suggesting that they are potentially preventable. Furthermore, the DPIC appears to have played a significant triaging role in toxic exposures; providing reassurance for minor poisoning cases while facilitating the appropriate referral of the more severe ones.
Background
Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoi... more Background Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoisomeric pairs of cyhalothrin, containing an alpha-cyano group. Taurine or 2-aminoethane sulfonic acid is a sulfur-containing α-amino acid that is the most abundant free amino acid in most mammal tissue. Aim and Objectives The present study was focused to investigate lambda-cyhalothrin induced nephrotoxicity and renal oxidative stress as well as to evaluate the alleviating role of taurine in this condition. Methods Lambda-cyhalothrin was administered orally at two dose levels (10.83 and 15.17 mg/kg body weight) alone or in combination after pre-treatment of taurine (50 mg/kg body weight) for consecutive 14 days. Results Renal toxicity was measured by a significant decrease in renal index, reduction in kidney protein and an increase in serum protein in lambda-cyhalothrin intoxicated rats. At the same time, lambda-cyhalothrin induced a significant renal oxidative stress demonstrated by elevated renal malondialdehyde content and oxidized glutathione level accompanied by a reduction in reduced glutathione and antioxidant enzymes in rats. Lambda-cyhalothrin induced renal toxicity and oxidative stress in the rat was significantly ameliorated due to the administration of taurine as an antidote. Conclusion All of these findings of the present study strongly suggest the protective role of taurine in the pathophysiology of lambda-cyhalothrin-induced renal toxicity and oxidative stress.
Homocysteine (HCY) is a non-protein sulfur-containing amino acid. It has received a great deal of... more Homocysteine (HCY) is a non-protein sulfur-containing amino acid. It has received a great deal of attention over the last two decades within the scientific community for its unique role in the induction of several diseases ranging from atherosclerotic cardiovascular disease to neural tube defects (NTD). The hypothesis that hyperhomocysteinemia (HHCY) causes atherosclerosis was proposed by McCully1 in 1969, when he observed that children with homocysteinuria had atherosclerotic plaques of the peripheral, coronary, and cerebral vasculature. In 1976, the initial epidemiological study of Wilcken and Wilcken 2 supported this hypothesis and provided the first evidence of the pathogenic role of HCY in atherosclerotic cardiovascular disease and alcoholism. HCY strictly associated with alcohol consumption and enhanced the alcohol consumption that leads to alcohol-related disorders such as brain atrophy, epileptic seizures during withdrawal, and mood disorders.3 Although, HHCY involves both genetic and nutritional causes,4 the mechanism of HCY toxicity is not completely understood.
Background: Pesticides are used frequently and may have various adverse effects on human health i... more Background: Pesticides are used frequently and may have various adverse effects on human health in different ways. Cypermethrin (CYP) is a synthetic type II pyrethroid pesticide that has been used extensively to control a wide variety of pests in agriculture, forestry, horticulture, and public health. Objectives: This study aimed to investigate the dose-dependent hematological, hepatic and gonadal toxicity of CYP in mature male and female Wistar rats. Methods: Rats were randomly divided into nine groups, different doses of CYP were administered for 14 consecutive days and different hematological, hepatic and gonadal parameters were assayed. Results: Erythrocyte count, hemoglobin percentage, hepatic reduced glutathione (GSH) content and sperm count were significantly diminished. Serum aspartic and alanine transaminase, hepatic malondialdehyde (MDA), testicular cholesterol content were increased following CYP treatment in male rats at 40 and 80 mg/kg body weight (1/9 and 1/4.5 LD 50). Elevated ovarian cholesterol content and decreased 17β hydroxy steroid dehydrogenase (HSD) levels were also observed in CYP-exposed female rats at a dose level of 34.33 and 51.5 mg/kg body wt. (1/9 and 1/6 LD 50). Conclusion: Taken together, CYP initiated hematological, hepatic and gonadal toxicity in mature male rats with a body weight of 40 mg/kg (1/9 LD 50) and gonadal toxicity in mature female rats with a body weight of 34.33 mg/kg (1/9 LD 50) and above.
Background: Pollution of aquatic ecosystems with heavy metals leads to decrease of the biodiversi... more Background: Pollution of aquatic ecosystems with heavy metals leads to decrease of the biodiversity and accumulation of toxicants in the food chain. Species of the genus Scenedesmus are sensitive indicators of environmental changes and have been used for the evaluation of risk factors for contamination of aquatic ecosystems. The microalga Scenedesmus incrassatulus can remove chromium and cadmium from the growth medium. Also, mammalian cell lines are another type of test system that has been used to study the mechanisms of heavy metal toxicity. However, little is known about the sensitivity and potential application of different human cell lines for bio-monitoring of heavy metal contamination. Aim: To investigate the toxicity of increasing concentrations of cadmium, nickel and lead on the green microalga Scenedesmus incrassatulus and the human cell lines HeLa, A549, FL, and Caco-2. Materials and Methods: To evaluate the toxic effects of Cd, Ni, and Pb, two test systems were used: an algal culture of S. incrassatulus and four human cell lines. For the algal system, the growth of the algae and the features such as "cell number in the coenobium/single cells", "po-sition of the inner cells in the coenobium", and "shape of the peripheral cell", were assessed. For the human cell cultures, the methyl-thiazol-tetrazolium (MTT) and neutral red assays were performed. In both the systems, the effects were measured at different time points (24, 48, and 72 hours) of treatment. Results: The experimental observations showed that lead exposure in maximal permissible levels (MPL) inhibited the growth of the green algae S. incrassatulus, while cadmium had a stimulating effect even at lower test concentrations. Cadmium and nickel treatment affected the morphological features "cell number in the coenobium/single cells" and "position of the inner cells in the coenobium". Regarding "shape of the peripheral cell", lead had the most significant effect after 24 h of treatment, which was expressed in reduction of the type "incrassatulus" compared to the type "obliquus". Cytotoxic effects of the heavy metals were also observed for all tested human cell lines. HeLa, FL and Caco-2 were most sensitive to cadmium compared to lead, while A549 cells showed equal sensitivity to all three heavy metals. Conclusion: The reported data presented specific impacts on the studied parameters for both the test-systems. The present study concluded that the green alga S. incrassatulus could be used as an effective test system for the biomonitoring of lead pollution. The cell line A549 can serve as a sensitive test system for the presence of cadmium, nickel and lead.
Aim: To determine the interaction of over-the-counter (OTC) and illicit psychostimulants at the c... more Aim: To determine the interaction of over-the-counter (OTC) and illicit psychostimulants at the cytochrome P450 enzyme, CYP2D6. CYP2D6 is responsible for 20% of hepatic Phase I metabolism and is a site of drug drug interactions, leading to increased drug toxicity. Materials and Methods: We examined the effects the OTC drugs; 1) the prototype H2-antagonist cimetidine (CMT) and 2) the opioid agonist cough suppressant dextromethorphan (DEX); as well as two scheduled drugs, methamphetamine (MA) and 3,4 methylenedioxymethamphetamine (MDMA) for their ability to interfere with CYP2D6 activity. Assays with human CYP2D6 determined the inhibitory potential (IC50) of each drug. Kinetic analysis (Vmax and Km) was accomplished using rodent hepatic microsomes. Results: Maximum inhibition of CYP2D6 activity following exposure to CMT+MDMA was significantly reduced 75-85% compared to quinidine (control) values. These data showed inhibitory effects in CYP2D6 activity in each compound tested. Alterations in CYP2D6 activity may result in complex drug-drug interactions leading to elevated plasma levels of drugs and increased risk for toxicity. Assays using rat CYP2D2 demonstrated Vmax elevations in the CMT group (493%) compared to control (naïve, no treatment) values (19.9±5.1 pmol/mg protein/min). The Km was increased 218% in CMT compared to controls (3.1±0.5 μM). Collectively, all MA challenged groups exhibited increases in total enzyme [Vmax; 280-490%] and affinity [Km; 165-220%] values compared to the control group. The increase in both Vmax and Km suggests that the low affinity/high capacity CYP2D2 isoform is upregulated. Conclusion: Our findings suggest that in vivo, MA acts as a CYP2D2-inducer, which will lead to altered secondary drug metabolism, increasing the risk of drug-related toxicity. Coupled with the ability of CMT and DEX to interfere with MA metabolism, a complex drug-drug interaction is possible, leading to increased toxicity. Our findings substantiate the hypothesis that the combination of illicit and OTC drugs could result in complex drug-drug interactions increasing the risk for severe drug-related toxicity.
Background: Human identification requires the maintenance of population databases of short tandem... more Background: Human identification requires the maintenance of population databases of short tandem repeat (STR) loci that allow for their correct interpretation during paternity testing and forensic cases. Material and Methods: We analyzed 15 STR loci with the AmpFlSTR ® Identifiler kit in a Mestizo (admixed) population sample from the state of Guerrero (South Mexico). Results: We estimated the allele distribution and different forensic parameters in this population. Genotype distribution was in agreement with the Hardy-Weinberg expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated no association between the pair of loci. The power of exclusion and power of discrimination values were 99.9994% and >99.99999%, respectively. Interpopulation analysis suggested that the Mestizo populations from the Central and the Southern regions conform one population cluster, separated from the Southeastern and Northwestern regions. Conclusions: We describe the genetic structure of Mexican Mestizos based on 15 STRs reporting for the first time a population representing the Southern region.
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Papers by Toxicology and Forensic Medicine – Open Journal
Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology.
Aims
In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice.
Results
For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables.
Conclusion
In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.
Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose.
Case Presentation
A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced.
Conclusion
Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.
Environmental toxicants have become a major source of health hazards to humans, thereby negatively impacting the health and overall well-being of exposed individuals. Among these environmental toxicants, heavy metals stand out as the major cause of tissue pathologies and threaten an individual’s health status. One such heavy metal is cadmium (CD) whose exposure has been linked to various tissue toxicities including nervous, respiratory, reproductive, cardiovascular, hepatic and renal tissues. Cadmium is a non-biodegradable heavy metallic which possesses a long half of lifestyles and comfortably accumulates inside the tissues in which it produces tissue toxicities main to tissue disorder. The present study was aimed to determine the amelioration capabilities of Vitamin C, E and Zinc from the harmful effects of CD in Wistar rats.
Methods
The Wistar strain male albino rats weighing 225±10 g were administered with CD along co-administered with Vitamin C, E and Zinc, individually and also in combinations. After the completion of 45-days of experimentation, certain specific enzymatic parameters were assayed in plasma serum to assess the impact of CD and protective effect of Vitamin C, E and Zinc.
Results
Soon after the co-administration of CD along with Vitamin C, E and Zinc, either individually and in combinations, Body weights, liver weight and histo-somatic index (HSI) of liver and certain specific enzymes of plasma including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, glucose and urea were monitored. All the parameters monitored showed a significant (p< 0.05) increase during CD administration except ALP. All the parameters selected in the present study were shown to be significantly (p< 0.05) reversed due to co-administration of Vitamin C, E and Zinc either individually or in combination, due to the protective effect from CD toxicity in wistar rats.
Conclusion
Our results demonstrate that co-administration of Vitamin C, E and Zinc ably protects the toxicity of CD in Wistar rats significantly.
The present study investigated the effects of cypermethrin exposure on humoral and cellular immune response in rat and its attenuation by zinc and alpha-lipoic acid.
Methods
Cypermethrin at the dose levels of 40 mg and 80 mg/kg body weight were orally administered and pre-treatment of zinc (227 mg/L in drinking water) and alpha-lipoic acid (35 mg/kg body wt.) were done. Total leukocyte and differential leukocyte counts (DLC), phagocytic index, serum nitric oxide (NO) activity, total immunoglobulin concentration, quantitative hemolysis, proliferation assay of blood mononuclear cells were estimated and histological examination of spleen was accomplished.
Results
Total white blood cell (WBC) count and percentage of lymphocyte, serum nitric oxide activity (p<0.001) and quantitative hemolysis were increased significantly increased whereas neutrophil %, total serum immunoglobulin, and blood mononuclear cell proliferation (p<0.001) and the phagocytic function of peritoneal macrophages were significantly reduced in cypermethrin treated rats compared to control group rats at a dose-dependent manner. Zinc and alpha-lipoic acid pre-treatment reversed the results.
Conclusion
From the findings it can be concluded that the co-administration of zinc and alpha-lipoic acid significantly attenuated the immunotoxic effects in cypermethrin exposed rat.
Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial.
Aim
Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication.
Method
The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading.
Results
Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007).
Conclusion
This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.
Decontamination is a critical medical counter measure in reducing toxic exposure following poisoning. Little is known on the effectiveness of this procedure and its impact in the context of preventing secondary exposure of healthcare workers and secondary contamination of facilities. Presented here is a case of dimethoate poisoning that required a prolonged period of skin decontamination to remove residual skin contamination.
Case Report
A young gardener consumed dimethoate at the workplace witnessed by a colleague who called the emergency services immediately. Paramedics noted the patient to be drowsy with stable vital signs and 100% oxygen saturation. En-route to the hospital the patient vomited multiple times and was drenched in vomitus with a pungent odour. Upon arrival at the emergency department (ED), vital signs remained stable with a Glasgow Coma Scale (GCS) of 10. Due to gross external contamination from the vomitus and pungent odours emanating suggestive of chemical fumes off-gassing, the hospital decontamination shower was activated for patient decontamination. Staff donned protective suits and proceeded to disrobe and bag all the patient’s clothing before showering the patient for 10-minutes using soap and water. Post-decontamination a chemical agent monitor (CAM) were used to screen for residual chemicals following the hospital’s decontamination protocol. The chemical alarm was triggered twice, first around the left mastoid region and again just below the left breast. This required targeted re-showering for a further 10-minutes before patient was finally cleared of contamination. Subsequently, the patient was given atropine (2.4 mg) and pralidoxime (1 g) followed by an infusion at the intensive care unit (ICU). The patient made an uneventful recovery and was discharged 5-days later.
Conclusion
This case of dimethoate poisoning is notable for the prolonged period of skin decontamination to remove residual skin contamination and illustrates potential implications to patient and health care worker safety. Past mass casualty incidents involving chemicals, such as the sarin attack in Tokyo, highlight the high incidence of secondary exposures amongst healthcare workers due to the lack of casualty decontamination. As a result, many hospitals have developed capacity to conduct rapid and timely decontamination at their premises to prevent further complications from secondary chemical exposure. However, the effectiveness of this process of decontamination needs further evaluation.
A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix for monitoring prescription and illicit drugs in a clinical setting on patients undergoing pain and addiction treatment. The current standard for monitoring patients’ medication use, misuse, and diversion is urine drug testing (UDT).
Materials and Methods
This study compared 632 paired urine and fingerstick blood specimens collected at three pain management clinics and one suboxone clinic for 35 drugs and/or metabolites. Plasma from the fingerstick blood was used for the analysis. The urine and plasma specimens were analyzed by validated liquid chromatography–tandem mass spectrometry (LC-MS-MS) procedures. The urine cutoff used by most pain testing laboratories were used to identify positive and negative drugs in urine. Limit of quantitation was used to identify positive and negative drugs in plasma. Drugs and/or metabolites were quantified in both urine and plasma using deuterium-labeled internal standards.
Results
Results were tabulated for urine and plasma specimens for data analysis. The results showed that 8.7% of plasma specimens detected more drugs compared to the corresponding urine specimens, and 2.2% of the urine specimens detected a drug that was negative in the corresponding plasma specimen. Overall 89.1% of the specimens had complete agreement between urine and plasma specimens for detection. The observed Cohen’s Kappa value for overall drug detection was 0.96 an “almost perfect” agreement as characterized by Landis and Koch.
Conclusion
Based on the observed data, the authors conclude that plasma collected from fingerstick blood is a better matrix to monitor patients currently prescribed pain medications or patients currently undergoing medication-assisted opioid treatment compared to urine drug testing.
An intricate relationship exists between the mitochondrial function and proteasome activity. Our recent report showed in a rat model of renal transplantation that mitochondrial dysfunction precedes compromised proteasome function and this results in a vicious cycle of mitochondrial injury and proteasome dysfunction. In this study, we studied whether reactive oxygen species (ROS) has a role in proteasome alteration in renal cells and vice versa.
Methods
We used the genomic and pharmacologic approach on rat normal kidney proximal tubular (NRK) cell lines. First, we knocked down β5 or Rpt6 subunit of the proteasome using small interfering RNA (siRNA) in NRK cells. We also treated NRK cells with Bortezomib, a proteasome inhibitor, and peroxynitrite (a potent ROS).
Results
Studies with RNA interference showed increased mitochondrial ROS following knockdown of β5 or Rpt6 subunit in NRK cells. Similarly, pharmacological inhibition of the proteasome in NRK cells using Bortezomib also showed an increase of mitochondrial ROS in a dose-dependent manner. Next, exposing NRK cells to different concentrations of peroxynitrite provided evidence that the higher levels of peroxynitrite exposure decreased the key subunits (β5 and α3) of the proteasome in NRK cells.
Conclusion
Our results suggest that proteasome inhibition/downregulation increases ROS, which then impairs proteasome subunits in renal proximal tubular cells.
The aim of this study was to review poisonings through the perspective of this poison center.
Method
A retrospective review of records in the DPIC call database was made covering the 4 years of its operation. Drug information and adverse effects calls were excluded from the study.
Results
There was a total of 15227 calls to the DPIC over the study period. Of these, 1817 calls (11.9%) were on acute toxic exposures involving patients. Healthcare personnel working in public restructured hospitals were the most frequent users (71.4%) of the service with the majority of these calls originating from the emergency departments (86%). Public inquiries accounted for 16.6% of the call volume. The cohort of poisoning cases showed a bimodal distribution of age groups with peaks in the less than 5 age group and the 20 to 40 year age group. The racial distribution followed local population demographics but with almost equal gender representation (50.3%males). Most exposures were accidental (67.4%) and occurred at home (69%). The number of agents involved in each exposure ranged from one (84.5%) to a maximum of 6 (<1%) agents. The common exposures involved analgesics (13.5%), antidepressants and sedatives (10.6%), industrial chemicals (5.7%) and bites and stings (8.4%). The calls were evenly distributed by month of the year with no significant seasonal variation although the daily distribution showed a peak in the late evening. The DPIC was able to complete immediate definitive advice within 15 minutes of the call in most situations (96.5%). Majority of public calls (69.2%) ended with reassurance and advice to observe for relevant symptoms. A similar disposition was observed even when the calls were from physicians.
Conclusion
In summary, poisonings were mostly accidental and affected the younger population suggesting that they are potentially preventable.
Furthermore, the DPIC appears to have played a significant triaging role in toxic exposures; providing reassurance for minor poisoning cases while facilitating the appropriate referral of the more severe ones.
Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoisomeric pairs of cyhalothrin, containing an alpha-cyano group. Taurine or 2-aminoethane sulfonic acid is a sulfur-containing α-amino acid that is the most abundant free amino acid in most mammal tissue.
Aim and Objectives
The present study was focused to investigate lambda-cyhalothrin induced nephrotoxicity and renal oxidative stress as well as to evaluate the alleviating role of taurine in this condition.
Methods
Lambda-cyhalothrin was administered orally at two dose levels (10.83 and 15.17 mg/kg body weight) alone or in combination after pre-treatment of taurine (50 mg/kg body weight) for consecutive 14 days.
Results
Renal toxicity was measured by a significant decrease in renal index, reduction in kidney protein and an increase in serum protein in lambda-cyhalothrin intoxicated rats. At the same time, lambda-cyhalothrin induced a significant renal oxidative stress demonstrated by elevated renal malondialdehyde content and oxidized glutathione level accompanied by a reduction in reduced glutathione and antioxidant enzymes in rats. Lambda-cyhalothrin induced renal toxicity and oxidative stress in the rat was significantly ameliorated due to the administration of taurine as an antidote.
Conclusion
All of these findings of the present study strongly suggest the protective role of taurine in the pathophysiology of lambda-cyhalothrin-induced renal toxicity and oxidative stress.
Aim: To investigate the toxicity of increasing concentrations of cadmium, nickel and lead on the green microalga Scenedesmus incrassatulus and the human cell lines HeLa, A549, FL, and Caco-2.
Materials and Methods: To evaluate the toxic effects of Cd, Ni, and Pb, two test systems were used: an algal culture of S. incrassatulus and four human cell lines. For the algal system, the growth of the algae and the features such as "cell number in the coenobium/single cells", "po-sition of the inner cells in the coenobium", and "shape of the peripheral cell", were assessed. For the human cell cultures, the methyl-thiazol-tetrazolium (MTT) and neutral red assays were performed. In both the systems, the effects were measured at different time points (24, 48, and 72 hours) of treatment.
Results: The experimental observations showed that lead exposure in maximal permissible levels (MPL) inhibited the growth of the green algae S. incrassatulus, while cadmium had a stimulating effect even at lower test concentrations. Cadmium and nickel treatment affected the morphological features "cell number in the coenobium/single cells" and "position of the inner cells in the coenobium". Regarding "shape of the peripheral cell", lead had the most significant effect after 24 h of treatment, which was expressed in reduction of the type "incrassatulus" compared to the type "obliquus". Cytotoxic effects of the heavy metals were also observed for all tested human cell lines. HeLa, FL and Caco-2 were most sensitive to cadmium compared to lead, while A549 cells showed equal sensitivity to all three heavy metals.
Conclusion: The reported data presented specific impacts on the studied parameters for both the test-systems. The present study concluded that the green alga S. incrassatulus could be used as an effective test system for the biomonitoring of lead pollution. The cell line A549 can serve as a sensitive test system for the presence of cadmium, nickel and lead.
Materials and Methods: We examined the effects the OTC drugs; 1) the prototype H2-antagonist cimetidine (CMT) and 2) the opioid agonist cough suppressant dextromethorphan (DEX); as well as two scheduled drugs, methamphetamine (MA) and 3,4 methylenedioxymethamphetamine (MDMA) for their ability to interfere with CYP2D6 activity. Assays with human CYP2D6 determined the inhibitory potential (IC50) of each drug. Kinetic analysis (Vmax and Km) was accomplished using rodent hepatic microsomes.
Results: Maximum inhibition of CYP2D6 activity following exposure to CMT+MDMA was significantly reduced 75-85% compared to quinidine (control) values. These data showed inhibitory effects in CYP2D6 activity in each compound tested. Alterations in CYP2D6 activity may result in complex drug-drug interactions leading to elevated plasma levels of drugs and increased risk for toxicity. Assays using rat CYP2D2 demonstrated Vmax elevations in the CMT group (493%) compared to control (naïve, no treatment) values (19.9±5.1 pmol/mg protein/min). The Km was increased 218% in CMT compared to controls (3.1±0.5 μM). Collectively, all MA challenged groups exhibited increases in total enzyme [Vmax; 280-490%] and affinity [Km; 165-220%] values compared to the control group. The increase in both Vmax and Km suggests that the low affinity/high capacity CYP2D2 isoform is upregulated.
Conclusion: Our findings suggest that in vivo, MA acts as a CYP2D2-inducer, which will lead to altered secondary drug metabolism, increasing the risk of drug-related toxicity. Coupled with the ability of CMT and DEX to interfere with MA metabolism, a complex drug-drug interaction is possible, leading to increased toxicity. Our findings substantiate the hypothesis that the combination of illicit and OTC drugs could result in complex drug-drug interactions increasing the risk for severe drug-related toxicity.
Material and Methods: We analyzed 15 STR loci with the AmpFlSTR ® Identifiler kit in a Mestizo (admixed) population sample from the state of Guerrero (South Mexico).
Results: We estimated the allele distribution and different forensic parameters in this population. Genotype distribution was in agreement with the Hardy-Weinberg expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated no association between the pair of loci. The power of exclusion and power of discrimination values were 99.9994% and >99.99999%, respectively. Interpopulation analysis suggested that the Mestizo populations from the Central and the Southern regions conform one population cluster, separated from the Southeastern and Northwestern regions.
Conclusions: We describe the genetic structure of Mexican Mestizos based on 15 STRs reporting for the first time a population representing the Southern region.
Snakebite is a collective health problem that afflicts areas with poor healthcare coverage. Venezuela has an important population of snakes, including the endemic species Crotalus vegrandis and Crotalus pifanorum, whose venom has not been fully characterized, especially of those aspects related to cardiac electrophysiology.
Aims
In this sense, this work aims to characterize the electrocardiographic and histopathological effect of crude venom of C. vegrandis and C. pifanorum on albino Naval Medical Research Institute (NMRI) mice.
Results
For this, mice were gathered in C. pifanorum and C. vegrandis experimental groups, including normal controls and envenomed mice injected with commercial antivenom. C. vegrandis venom showed a significant T and S wave flattening and pulmonic (pulmonary) regurgitation (PR) enlargement, in addition to atrial ectopic activity, notched R wave, triggered activity, and T wave inversion. C. pifanorum was the only group that registered triggered activity. Antivenom was able to revert conduction disorders showing a statistical increase in arrhythmogenic compared by χ2 . The multidimensional comparison confirmed the statistical differences between C. vegrandis and C. pifanorum venoms and between antivenom vs non-antivenom groups, detecting variables associated with cardiac conduction, as the most important variables.
Conclusion
In conclusion, this work demonstrated, as far as we know, for the first time the cardiotoxic effects associated with C. vegrandis and C. pifanorum venom injection, subsequently suggesting the duty of including an electrocardiogram in the consultation of any accident caused by these species.
Theophylline poisoning leads to multisystem toxicity. Management of theophylline overdose is focused on stabilizing cardiovascular manifestations of arrhythmia and hypotension, correcting metabolic derangements, aborting seizures and removing the drug from the system. We present a case of refractory seizures and haemodynamic instability from theophylline poisoning and reviewed the literature to update the management of severe theophylline overdose.
Case Presentation
A 73-year-old Chinese gentleman presenting with chills and rigor was admitted for management of sepsis. While admitted suffered seizures which were refractory to benzodiazepine and anti-epileptic drugs. Based on his previous admission for theophylline overdose, serum levels were done confirming severe theophylline poisoning. He was resuscitated and subsequently started on haemodialysis following which seizures were eventually aborted when theophylline levels were successfully reduced.
Conclusion
Severe theophylline poisoning should be identified early and appropriate treatment initiated promptly. In the management of refractory hypotension, methylene blue and venoarterial-extracorporeal membrane oxygenation are reasonable rescue therapies to consider. Multi-dose activated charcoal and extracorporeal treatments for elimination of drugs should be administered in severe theophylline poisoning.
Environmental toxicants have become a major source of health hazards to humans, thereby negatively impacting the health and overall well-being of exposed individuals. Among these environmental toxicants, heavy metals stand out as the major cause of tissue pathologies and threaten an individual’s health status. One such heavy metal is cadmium (CD) whose exposure has been linked to various tissue toxicities including nervous, respiratory, reproductive, cardiovascular, hepatic and renal tissues. Cadmium is a non-biodegradable heavy metallic which possesses a long half of lifestyles and comfortably accumulates inside the tissues in which it produces tissue toxicities main to tissue disorder. The present study was aimed to determine the amelioration capabilities of Vitamin C, E and Zinc from the harmful effects of CD in Wistar rats.
Methods
The Wistar strain male albino rats weighing 225±10 g were administered with CD along co-administered with Vitamin C, E and Zinc, individually and also in combinations. After the completion of 45-days of experimentation, certain specific enzymatic parameters were assayed in plasma serum to assess the impact of CD and protective effect of Vitamin C, E and Zinc.
Results
Soon after the co-administration of CD along with Vitamin C, E and Zinc, either individually and in combinations, Body weights, liver weight and histo-somatic index (HSI) of liver and certain specific enzymes of plasma including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, glucose and urea were monitored. All the parameters monitored showed a significant (p< 0.05) increase during CD administration except ALP. All the parameters selected in the present study were shown to be significantly (p< 0.05) reversed due to co-administration of Vitamin C, E and Zinc either individually or in combination, due to the protective effect from CD toxicity in wistar rats.
Conclusion
Our results demonstrate that co-administration of Vitamin C, E and Zinc ably protects the toxicity of CD in Wistar rats significantly.
The present study investigated the effects of cypermethrin exposure on humoral and cellular immune response in rat and its attenuation by zinc and alpha-lipoic acid.
Methods
Cypermethrin at the dose levels of 40 mg and 80 mg/kg body weight were orally administered and pre-treatment of zinc (227 mg/L in drinking water) and alpha-lipoic acid (35 mg/kg body wt.) were done. Total leukocyte and differential leukocyte counts (DLC), phagocytic index, serum nitric oxide (NO) activity, total immunoglobulin concentration, quantitative hemolysis, proliferation assay of blood mononuclear cells were estimated and histological examination of spleen was accomplished.
Results
Total white blood cell (WBC) count and percentage of lymphocyte, serum nitric oxide activity (p<0.001) and quantitative hemolysis were increased significantly increased whereas neutrophil %, total serum immunoglobulin, and blood mononuclear cell proliferation (p<0.001) and the phagocytic function of peritoneal macrophages were significantly reduced in cypermethrin treated rats compared to control group rats at a dose-dependent manner. Zinc and alpha-lipoic acid pre-treatment reversed the results.
Conclusion
From the findings it can be concluded that the co-administration of zinc and alpha-lipoic acid significantly attenuated the immunotoxic effects in cypermethrin exposed rat.
Tramadol is a synthetic centrally acting analgesic used worldwide for pain relief, but now abused as a euphoria generating substance. The short- and long-term implications of tramadol intoxication on blood cells and its components are still hazy and controversial.
Aim
Our primary aim was to evaluate the alterative pattern of haematological parameters resulting from acute or chronic tramadol intoxication.
Method
The study was made of acute and chronic phases of sixty male rats (Rattusnorvegicus) randomly pair-divided into established groups of six male rats each. The acute stage consisted of a control group of 6 rats administered with normal saline solution, and a treatment group of 6 rats administered with lethal dose of tramadol. The control group for the chronic stage consisted of 6 rats that were administered normal saline solution. Whereas, the tramadol-dependent groups comprised of 3 groups of 6 rats each administered orally with 50 mg/kg, 100 mg/kg, and 200 mg/kg of tramadol for 90 days respectively. Statistical analyses consisted of the one-way analysis of variance (ANOVA), Student’s t-test, and Pearson’s Correlation using the JMP statistical discovery™ software version 14.1. Blood samples were collected after anesthetic sacrifice by cardiac puncture for the analysis of full blood count and red cell indices using SYSMEX Automated Blood Count machine (SYSMEX KX-21N ANALYZER) and microscopy for blood film reading.
Results
Results of the acute phase of the study showed that the packed cell volume (PCV) in the treatment group (51.00±2.96%) was significantly higher (t=3.99, p=0.002) than control (37.83±1.43%). Similarly, the haemoglobin concentration (Hb) in the treatment group (14.70±0.46 g/dL) was significantly higher (t=5.10, p=0.005) than control (11.55±0.41 g/dL). The mean cell haemoglobin concentration (MCHC) was significantly lower (t=2.67, p=0.02) in the control group (28.30±0.52 g/dL) than treatment (30.43±0.61 g/dL). However, that of the chronic phase exhibited a progressive increase in platelet count which was proportional to increasing dosage of treatment (t=8.59, p=0.007).
Conclusion
This study has demonstrated that tramadol administration could cause haematological alterations which could be beneficial if administrated optimally and deleterious, if abused. Therefore, indiscriminate and prolonged use of tramadol should be monitored to avert haemotoxicity.
Decontamination is a critical medical counter measure in reducing toxic exposure following poisoning. Little is known on the effectiveness of this procedure and its impact in the context of preventing secondary exposure of healthcare workers and secondary contamination of facilities. Presented here is a case of dimethoate poisoning that required a prolonged period of skin decontamination to remove residual skin contamination.
Case Report
A young gardener consumed dimethoate at the workplace witnessed by a colleague who called the emergency services immediately. Paramedics noted the patient to be drowsy with stable vital signs and 100% oxygen saturation. En-route to the hospital the patient vomited multiple times and was drenched in vomitus with a pungent odour. Upon arrival at the emergency department (ED), vital signs remained stable with a Glasgow Coma Scale (GCS) of 10. Due to gross external contamination from the vomitus and pungent odours emanating suggestive of chemical fumes off-gassing, the hospital decontamination shower was activated for patient decontamination. Staff donned protective suits and proceeded to disrobe and bag all the patient’s clothing before showering the patient for 10-minutes using soap and water. Post-decontamination a chemical agent monitor (CAM) were used to screen for residual chemicals following the hospital’s decontamination protocol. The chemical alarm was triggered twice, first around the left mastoid region and again just below the left breast. This required targeted re-showering for a further 10-minutes before patient was finally cleared of contamination. Subsequently, the patient was given atropine (2.4 mg) and pralidoxime (1 g) followed by an infusion at the intensive care unit (ICU). The patient made an uneventful recovery and was discharged 5-days later.
Conclusion
This case of dimethoate poisoning is notable for the prolonged period of skin decontamination to remove residual skin contamination and illustrates potential implications to patient and health care worker safety. Past mass casualty incidents involving chemicals, such as the sarin attack in Tokyo, highlight the high incidence of secondary exposures amongst healthcare workers due to the lack of casualty decontamination. As a result, many hospitals have developed capacity to conduct rapid and timely decontamination at their premises to prevent further complications from secondary chemical exposure. However, the effectiveness of this process of decontamination needs further evaluation.
A clinical study was conducted to evaluate fingerstick blood as a viable biological matrix for monitoring prescription and illicit drugs in a clinical setting on patients undergoing pain and addiction treatment. The current standard for monitoring patients’ medication use, misuse, and diversion is urine drug testing (UDT).
Materials and Methods
This study compared 632 paired urine and fingerstick blood specimens collected at three pain management clinics and one suboxone clinic for 35 drugs and/or metabolites. Plasma from the fingerstick blood was used for the analysis. The urine and plasma specimens were analyzed by validated liquid chromatography–tandem mass spectrometry (LC-MS-MS) procedures. The urine cutoff used by most pain testing laboratories were used to identify positive and negative drugs in urine. Limit of quantitation was used to identify positive and negative drugs in plasma. Drugs and/or metabolites were quantified in both urine and plasma using deuterium-labeled internal standards.
Results
Results were tabulated for urine and plasma specimens for data analysis. The results showed that 8.7% of plasma specimens detected more drugs compared to the corresponding urine specimens, and 2.2% of the urine specimens detected a drug that was negative in the corresponding plasma specimen. Overall 89.1% of the specimens had complete agreement between urine and plasma specimens for detection. The observed Cohen’s Kappa value for overall drug detection was 0.96 an “almost perfect” agreement as characterized by Landis and Koch.
Conclusion
Based on the observed data, the authors conclude that plasma collected from fingerstick blood is a better matrix to monitor patients currently prescribed pain medications or patients currently undergoing medication-assisted opioid treatment compared to urine drug testing.
An intricate relationship exists between the mitochondrial function and proteasome activity. Our recent report showed in a rat model of renal transplantation that mitochondrial dysfunction precedes compromised proteasome function and this results in a vicious cycle of mitochondrial injury and proteasome dysfunction. In this study, we studied whether reactive oxygen species (ROS) has a role in proteasome alteration in renal cells and vice versa.
Methods
We used the genomic and pharmacologic approach on rat normal kidney proximal tubular (NRK) cell lines. First, we knocked down β5 or Rpt6 subunit of the proteasome using small interfering RNA (siRNA) in NRK cells. We also treated NRK cells with Bortezomib, a proteasome inhibitor, and peroxynitrite (a potent ROS).
Results
Studies with RNA interference showed increased mitochondrial ROS following knockdown of β5 or Rpt6 subunit in NRK cells. Similarly, pharmacological inhibition of the proteasome in NRK cells using Bortezomib also showed an increase of mitochondrial ROS in a dose-dependent manner. Next, exposing NRK cells to different concentrations of peroxynitrite provided evidence that the higher levels of peroxynitrite exposure decreased the key subunits (β5 and α3) of the proteasome in NRK cells.
Conclusion
Our results suggest that proteasome inhibition/downregulation increases ROS, which then impairs proteasome subunits in renal proximal tubular cells.
The aim of this study was to review poisonings through the perspective of this poison center.
Method
A retrospective review of records in the DPIC call database was made covering the 4 years of its operation. Drug information and adverse effects calls were excluded from the study.
Results
There was a total of 15227 calls to the DPIC over the study period. Of these, 1817 calls (11.9%) were on acute toxic exposures involving patients. Healthcare personnel working in public restructured hospitals were the most frequent users (71.4%) of the service with the majority of these calls originating from the emergency departments (86%). Public inquiries accounted for 16.6% of the call volume. The cohort of poisoning cases showed a bimodal distribution of age groups with peaks in the less than 5 age group and the 20 to 40 year age group. The racial distribution followed local population demographics but with almost equal gender representation (50.3%males). Most exposures were accidental (67.4%) and occurred at home (69%). The number of agents involved in each exposure ranged from one (84.5%) to a maximum of 6 (<1%) agents. The common exposures involved analgesics (13.5%), antidepressants and sedatives (10.6%), industrial chemicals (5.7%) and bites and stings (8.4%). The calls were evenly distributed by month of the year with no significant seasonal variation although the daily distribution showed a peak in the late evening. The DPIC was able to complete immediate definitive advice within 15 minutes of the call in most situations (96.5%). Majority of public calls (69.2%) ended with reassurance and advice to observe for relevant symptoms. A similar disposition was observed even when the calls were from physicians.
Conclusion
In summary, poisonings were mostly accidental and affected the younger population suggesting that they are potentially preventable.
Furthermore, the DPIC appears to have played a significant triaging role in toxic exposures; providing reassurance for minor poisoning cases while facilitating the appropriate referral of the more severe ones.
Lambda-cyhalothrin (LCT) is an isomeric form of the two biologically active diastereoisomeric pairs of cyhalothrin, containing an alpha-cyano group. Taurine or 2-aminoethane sulfonic acid is a sulfur-containing α-amino acid that is the most abundant free amino acid in most mammal tissue.
Aim and Objectives
The present study was focused to investigate lambda-cyhalothrin induced nephrotoxicity and renal oxidative stress as well as to evaluate the alleviating role of taurine in this condition.
Methods
Lambda-cyhalothrin was administered orally at two dose levels (10.83 and 15.17 mg/kg body weight) alone or in combination after pre-treatment of taurine (50 mg/kg body weight) for consecutive 14 days.
Results
Renal toxicity was measured by a significant decrease in renal index, reduction in kidney protein and an increase in serum protein in lambda-cyhalothrin intoxicated rats. At the same time, lambda-cyhalothrin induced a significant renal oxidative stress demonstrated by elevated renal malondialdehyde content and oxidized glutathione level accompanied by a reduction in reduced glutathione and antioxidant enzymes in rats. Lambda-cyhalothrin induced renal toxicity and oxidative stress in the rat was significantly ameliorated due to the administration of taurine as an antidote.
Conclusion
All of these findings of the present study strongly suggest the protective role of taurine in the pathophysiology of lambda-cyhalothrin-induced renal toxicity and oxidative stress.
Aim: To investigate the toxicity of increasing concentrations of cadmium, nickel and lead on the green microalga Scenedesmus incrassatulus and the human cell lines HeLa, A549, FL, and Caco-2.
Materials and Methods: To evaluate the toxic effects of Cd, Ni, and Pb, two test systems were used: an algal culture of S. incrassatulus and four human cell lines. For the algal system, the growth of the algae and the features such as "cell number in the coenobium/single cells", "po-sition of the inner cells in the coenobium", and "shape of the peripheral cell", were assessed. For the human cell cultures, the methyl-thiazol-tetrazolium (MTT) and neutral red assays were performed. In both the systems, the effects were measured at different time points (24, 48, and 72 hours) of treatment.
Results: The experimental observations showed that lead exposure in maximal permissible levels (MPL) inhibited the growth of the green algae S. incrassatulus, while cadmium had a stimulating effect even at lower test concentrations. Cadmium and nickel treatment affected the morphological features "cell number in the coenobium/single cells" and "position of the inner cells in the coenobium". Regarding "shape of the peripheral cell", lead had the most significant effect after 24 h of treatment, which was expressed in reduction of the type "incrassatulus" compared to the type "obliquus". Cytotoxic effects of the heavy metals were also observed for all tested human cell lines. HeLa, FL and Caco-2 were most sensitive to cadmium compared to lead, while A549 cells showed equal sensitivity to all three heavy metals.
Conclusion: The reported data presented specific impacts on the studied parameters for both the test-systems. The present study concluded that the green alga S. incrassatulus could be used as an effective test system for the biomonitoring of lead pollution. The cell line A549 can serve as a sensitive test system for the presence of cadmium, nickel and lead.
Materials and Methods: We examined the effects the OTC drugs; 1) the prototype H2-antagonist cimetidine (CMT) and 2) the opioid agonist cough suppressant dextromethorphan (DEX); as well as two scheduled drugs, methamphetamine (MA) and 3,4 methylenedioxymethamphetamine (MDMA) for their ability to interfere with CYP2D6 activity. Assays with human CYP2D6 determined the inhibitory potential (IC50) of each drug. Kinetic analysis (Vmax and Km) was accomplished using rodent hepatic microsomes.
Results: Maximum inhibition of CYP2D6 activity following exposure to CMT+MDMA was significantly reduced 75-85% compared to quinidine (control) values. These data showed inhibitory effects in CYP2D6 activity in each compound tested. Alterations in CYP2D6 activity may result in complex drug-drug interactions leading to elevated plasma levels of drugs and increased risk for toxicity. Assays using rat CYP2D2 demonstrated Vmax elevations in the CMT group (493%) compared to control (naïve, no treatment) values (19.9±5.1 pmol/mg protein/min). The Km was increased 218% in CMT compared to controls (3.1±0.5 μM). Collectively, all MA challenged groups exhibited increases in total enzyme [Vmax; 280-490%] and affinity [Km; 165-220%] values compared to the control group. The increase in both Vmax and Km suggests that the low affinity/high capacity CYP2D2 isoform is upregulated.
Conclusion: Our findings suggest that in vivo, MA acts as a CYP2D2-inducer, which will lead to altered secondary drug metabolism, increasing the risk of drug-related toxicity. Coupled with the ability of CMT and DEX to interfere with MA metabolism, a complex drug-drug interaction is possible, leading to increased toxicity. Our findings substantiate the hypothesis that the combination of illicit and OTC drugs could result in complex drug-drug interactions increasing the risk for severe drug-related toxicity.
Material and Methods: We analyzed 15 STR loci with the AmpFlSTR ® Identifiler kit in a Mestizo (admixed) population sample from the state of Guerrero (South Mexico).
Results: We estimated the allele distribution and different forensic parameters in this population. Genotype distribution was in agreement with the Hardy-Weinberg expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated no association between the pair of loci. The power of exclusion and power of discrimination values were 99.9994% and >99.99999%, respectively. Interpopulation analysis suggested that the Mestizo populations from the Central and the Southern regions conform one population cluster, separated from the Southeastern and Northwestern regions.
Conclusions: We describe the genetic structure of Mexican Mestizos based on 15 STRs reporting for the first time a population representing the Southern region.