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Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts... more
Cannabidiol (CBD), the most extensively studied non-intoxicating phytocannabinoid, has been attracting a lot of interest worldwide owing to its numerous beneficial effects. The aim of this study was to explore the effect that CBD exerts on the adenosinergic system of paced left atria isolated from obese type Zucker Diabetic Fatty (ZDF) rats, maintained on diabetogenic rat chow, received 60 mg/kg/day CBD or vehicle via gavage for 4 weeks. We found that N6-cyclopentyladenosine (CPA), a relatively stable and poorly transported A1 adenosine receptor agonist, elicited a significantly weaker response in the CBD-treated group than in the vehicle-treated one. In contrast, adenosine, a quickly metabolized and transported adenosine receptor agonist, evoked a significantly stronger response in the CBD-treated group than in the vehicle-treated counterpart (excepting its highest concentrations). These results can be explained only with the adenosine transport inhibitory property of CBD (and not ...
Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases... more
Impaired mitochondrial function is associated with several metabolic diseases and health conditions, including insulin resistance and type 2 diabetes (T2DM), as well as ageing. The close relationship between the above-mentioned diseases and cardiovascular disease (CVD) (diabetic cardiomyopathy and age-related cardiovascular diseases) has long been known. Mitochondria have a crucial role: they are a primary source of energy produced in the form of ATP via fatty acid oxidation, tricarboxylic acid (TCA) cycle, and electron transport chain (ETC), and ATP synthase acts as a key regulator of cardiomyocyte survival. Mitochondrial medicine has been increasingly discussed as a promising therapeutic approach in the treatment of CVD. It is well known that vitamin B3 as an NAD+ precursor exists in several forms, e.g., nicotinic acid (niacin) and nicotinamide (NAM). These cofactors are central to cellular homeostasis, mitochondrial respiration, ATP production, and reactive oxygen species generat...
Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential... more
Over the last decades, growing interest has turned to preventive and therapeutic approaches for achieving successful aging. Oxidative stress and inflammation are fundamental features of cardiovascular diseases; therefore, potential targets of them can improve cardiac outcomes. Our study aimed to examine the involvement of the endocannabinoid system, especially the CB1 receptor blockade, on inflammatory and oxidant/antioxidant processes. Twenty-month-old female and male Wistar rats were divided into rimonabant-treated and aging control (untreated) groups. Rimonabant, a selective CB1 receptor antagonist, was administered at the dose of 1 mg/kg/day intraperitoneally for 2 weeks. Cardiac amounts of ROS, the antioxidant glutathione and superoxide dismutase (SOD), and the activity and concentration of the heme oxygenase (HO) enzyme were detected. Among inflammatory parameters, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and myeloperoxidase (MPO) enzyme activity we...
Abstract: The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of... more
Abstract: The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2 % cholesterol, 12 weeks; GROUP IV, chow supplemented with 2 % cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to
Cardiovascular morbidity and mortality of premenopausal women are significantly lower compared to men of similar age. However, this protective effect evidently decreases after the onset of menopause. We hypothesized that physical exercise... more
Cardiovascular morbidity and mortality of premenopausal women are significantly lower compared to men of similar age. However, this protective effect evidently decreases after the onset of menopause. We hypothesized that physical exercise could be a potential therapeutic strategy to improve inflammatory processes and cardiovascular antioxidant homeostasis, which can be affected by the loss of estrogen and the adverse environmental factors, such as overnutrition. Ovariectomized (OVX, n= 40) and sham-operated (SO, n= 40) female Wistar rats were randomized to exercising (R) and non-exercising (NR) groups. Feeding parameters were chosen to make a standard chow (CTRL) or a high triglyceride diet (HT) for 12 weeks. Aortic and cardiac heme oxygenase (HO) activity and HO-1 concentrations significantly decreased in all of the NR OVX and SO HT groups. However, the 12-week physical exercise was found to improve HO-1 values. Plasma IL-6 concentrations were higher in the NR OVX animals and rats ...
The development and progression of hypertension are closely linked to an unhealthy lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the effects of diet and exercise on the elements of the... more
The development and progression of hypertension are closely linked to an unhealthy lifestyle; however, its underlying mechanisms are not fully elucidated. Our aim was to assess the effects of diet and exercise on the elements of the renin–angiotensin–aldosterone system (RAAS), redox-sensitive parameters, and the expression of the vascular tone regulator endothelial nitric oxide synthase (eNOS). Male control Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats were randomized based on the type of diet (standard chow, high-fat diet: HT, and fructose-enriched diet: HF) and exercise (voluntary wheel-running exercise or lack of exercise). After 12 weeks of experimental period, the concentrations of the RAAS elements, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) concentrations, levels of superoxide dismutase (SOD) and glutathione (GSH), and expressions of extracellular signal-regulated kinase1/2 (ERK1/2) and phosphorylated ERK1/2 as well as eN...
Vascular calcification associated with high plasma phosphate (Pi) level is a frequent complication of hyperglycemia, diabetes mellitus, and chronic kidney disease. BGP-15 is an emerging anti-diabetic drug candidate. This study was aimed... more
Vascular calcification associated with high plasma phosphate (Pi) level is a frequent complication of hyperglycemia, diabetes mellitus, and chronic kidney disease. BGP-15 is an emerging anti-diabetic drug candidate. This study was aimed to explore whether BGP-15 inhibits high Pi-induced calcification of human vascular smooth muscle cells (VSMCs) under normal glucose (NG) and high glucose (HG) conditions. Exposure of VSMCs to Pi resulted in accumulation of extracellular calcium, elevated cellular Pi uptake and intracellular pyruvate dehydrogenase kinase-4 (PDK-4) level, loss of smooth muscle cell markers (ACTA, TAGLN), and enhanced osteochondrogenic gene expression (KLF-5, Msx-2, Sp7, BMP-2). Increased Annexin A2 and decreased matrix Gla protein (MGP) content were found in extracellular vesicles (EVs). The HG condition markedly aggravated Pi-induced VSMC calcification. BGP-15 inhibited Pi uptake and PDK-4 expression that was accompanied by the decreased nuclear translocation of KLF-5...
The progression of coronary artery diseases in premenopausal women is lower than in age-matched men; however, its probability increases rapidly after menopause. The aim of our study was to investigate the postconditioning-like effects of... more
The progression of coronary artery diseases in premenopausal women is lower than in age-matched men; however, its probability increases rapidly after menopause. The aim of our study was to investigate the postconditioning-like effects of voluntary physical exercise on postmenopausal cardiovascular outcomes after myocardial infarction. We used fertile Wistar females [control (CTRL)] and pharmacologically induced estrogen-deficient (POVX; 750 µg/kg triptorelin im, every 4th week) rats. CTRL and POVX animals were randomly assigned to receive an injection of 0.1 mg isoproterenol (ISO)/kg. At the 20th hour after ISO injection, serum markers of myocardial injury, such as lactate dehydrogenase (LDH) and myoglobin, were measured. After a 3-wk resting period, ISO-treated and untreated animals were further divided into subgroups on the basis of 6 wk of physical exercise. At the end of the experiment, cardiac activity and content of the antioxidative heme oxygenase (HO) enzyme, levels of GSH a...
A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone... more
A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related to the heme oxygenase (HO) system. To determine the effects of testosterone, 10-week-old, and 24-month-old sham-operated and castrated male Wistar rats were used. One part of the castrated animals was daily treated with 2.5 mg/kg cyproterone acetate, while the hormone replacement therapy was performed via an i.m. injection of a dose of 8.0 mg testosterone undecanoate/kg/once a week. The plasma testosterone level, the activity of HO and myeloperoxidase (MPO) enzymes; the concentrations of the HO-1, tumor necrosis alpha (TNF-α), and cyclic guanosine monophosphate (cGMP), as well as the total level of glutathione (GSH + GSSG) were determined from the cardiac left ventricle. In accord...
3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical,... more
3D printing is attracting considerable interest for its capacity to produce prototypes and small production runs rapidly. Fused deposit modeling (FDM) was used to produce polyvalent test plates for investigation of the physical, chemical, and in-vitro biological properties of printed materials. The polyvalent test plates (PVTPs) are poly-lactic acid cylinders, 14 mm in diameter and 3 mm in height. The polymer ester backbone was surface modified by a series of ramified and linear oligoamines to increase its hydrophilicity and introduce a positive charge. The chemical modification was verified by FT-IR spectroscopy, showing the introduction of amide and amine functions, and contact angle measurements confirmed increased hydrophilicity. Morphology studies (SEM, optical microscopy) indicated that the modification of PVTP possessed a planar morphology with small pits. Positron annihilation lifetime spectroscopy demonstrated that the polymeric free volume decreased on modification. An MTT...
Aim. To evaluate tear film parameters and relationship of objective clinical signs and subjective symptoms of dry eye disease (DED) in inflammatory bowel disease (IBD) subgroups. Methods. 39 patients with Crohn’s disease (CD), 26 patients... more
Aim. To evaluate tear film parameters and relationship of objective clinical signs and subjective symptoms of dry eye disease (DED) in inflammatory bowel disease (IBD) subgroups. Methods. 39 patients with Crohn’s disease (CD), 26 patients with ulcerative colitis (UC), and 39 control persons with no ocular symptoms or surface disorders were included in this prospective, case-control, and cross-sectional study. The ocular surface disease index (OSDI) questionnaire was applied to evaluate dry eye symptoms, and objective tests of DED were performed on both eyes of each subject. Results. The average of OSDI scores was 30.59 (±16.68) in CD patients, 24.67 (±23.48) in UC patients, and 11.19 (±5.8) in controls. Except for tear film breakup time (tBUT) and Schirmer-I values other objective parameters were better in UC patients, than in CD patients. CD patients rather than UC patients tend to develop DED. This was associated with immunosuppressant and TNF-α inhibitor use. Conclusions. Clinici...
Atherosclerosis is strongly associated with cardiac dysfunction and heart failure. Besides microvascular dysfunction and diminishment of the cardiac nitric oxide-Protein Kinase G (NO-PKG) pathway, recent evidence suggests that... more
Atherosclerosis is strongly associated with cardiac dysfunction and heart failure. Besides microvascular dysfunction and diminishment of the cardiac nitric oxide-Protein Kinase G (NO-PKG) pathway, recent evidence suggests that phosphodiesterase 9A (PDE9A) enzyme has an unfavorable role in pathological changes. Here, we characterized a rabbit model that shows cardiac dysfunction as a result of an atherogenic diet, and examined the myocardial PDE9A signaling. Rabbits were divided into Control (normal diet) and HC (atherogenic diet) groups. Cardiac function was evaluated by echocardiography. Vascular function was assessed, along with serum biomarkers. Histological stains were conducted, expression of selected proteins and cyclic guanosine monophosphate (cGMP) levels were determined. Signs of diastolic dysfunction were shown in HC animals, along with concentric hypertrophy and interstitial fibrosis. Endothelial function was diminished in HC rabbits, along with marked reduction in the ao...
Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among... more
Among diabetes patients, ophthalmological complications are very frequent. High blood glucose and (consequential) ischemia-reperfusion (I/R) injury contribute significantly to the severity of retinopathies. Diabetic retinopathy is among the leading causes of blindness. Our study demonstrates the effect of sour cherry seed extract (SCSE) on blood glucose and function of the retina with electroretinography (ERG) in a diabetic setting with or without ischemia-reperfusion (I/R) injury in Zucker Diabetic Fatty (ZDF) rats. Our results prove that the SCSE has a retinoprotective effect in diabetic rats: according to ERG measurements, SCSE treatment mitigated the retinal function-damaging effect of diabetes, and proved to be protective in the diabetic eye against ischemia-reperfusion injuries of the retina. Outcomes suggest that the protective effects of SCSE may occur through several pathways, including HO-1 dependent mechanisms. The observation that SCSE treatment decreases blood glucose i...
At birth, the vestibular system is fully mature, whilst higher order sensory processing is yet to develop in the full-term neonate. The current paper lays out a theoretical framework to account for the role vestibular stimulation may have... more
At birth, the vestibular system is fully mature, whilst higher order sensory processing is yet to develop in the full-term neonate. The current paper lays out a theoretical framework to account for the role vestibular stimulation may have driving multisensory and sensorimotor integration. Accordingly, vestibular stimulation, by activating the parieto-insular vestibular cortex, and/or the posterior parietal cortex may provide the cortical input for multisensory neurons in the superior colliculus that is needed for multisensory processing. Furthermore, we propose that motor development, by inducing change of reference frames, may shape the receptive field of multisensory neurons. This, by leading to lack of spatial contingency between formally contingent stimuli, may cause degradation of prior motor responses. Additionally, we offer a testable hypothesis explaining the beneficial effect of sensory integration therapies regarding attentional processes. Key concepts of a sensorimotor in...
One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and... more
One of the most promising emerging innovations in personalized medication is based on 3D printing technology. For use as authorized medications, 3D-printed products require different in vitro tests, including dissolution and biocompatibility investigations. Our objective was to manufacture implantable drug delivery systems using fused deposition modeling, and in vitro tests were performed for the assessment of these products. Polylactic acid, antibacterial polylactic acid, polyethylene terephthalate glycol, and poly(methyl methacrylate) filaments were selected, and samples with 16, 19, or 22 mm diameters and 0%, 5%, 10%, or 15% infill percentages were produced. The dissolution test was performed by a USP dissolution apparatus 1. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide dye (MTT)-based prolonged cytotoxicity test was performed on Caco-2 cells to certify the cytocompatibility properties. The implantable drug delivery systems were characterized by thermogravim...
Active screening for resistant multidrug strain carriers remains an important component of infection control policy in any healthcare setting indifferent of financial and logistical costs. The objective of our study was to determine the... more
Active screening for resistant multidrug strain carriers remains an important component of infection control policy in any healthcare setting indifferent of financial and logistical costs. The objective of our study was to determine the spectrum of bacterial colonization individually among intensive care unit patients. A retrospective observational study was performed in the Intensive Care Unit of Emergency Clinical County Hospital of Oradea during 2017. Medical records of the patients were used for evaluation of source of ICU admission, previous antibiotic therapy, comorbidities, and length of hospital stay. Nasal and groin swabs for MRSA detection and rectal swabs for ESBL, VRE, and CRE detection were collected upon ICU admission of all patients in the first 24 hours and after 7 days. Swab samples were processed for isolation and identification of these resistant multidrug strains. Bacterial colonization on admission was detected in a quarter of patients included in the study. Car...
Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from... more
Fenugreek is a common herb possessing several bioactive components including diosgenin. Here, dietary fenugreek seed flour and diosgenin were evaluated on a model of endothelium-dependent vasorelaxation by abdominal aortas isolated from rats receiving high-fat, high-sugar diet (HFHSD). 60 male Wistar rats were randomized into six groups: (i) negative control getting conventional rat feed regimen; (ii) positive control receiving HFHSD; (iii) a test group fed 2 g/kg bw/day fenugreek seed flour (containing 10 mg/kg bw/day diosgenin) + HFHSD; (iv) three test groups fed 1, 10 and 50 mg/kg bw/day diosgenin + HFHSD. Alimentary treatments were carried out for six weeks. The abdominal aortas were isolated, and 2 mm wide rings were sectioned off and mounted at a resting tension of 10 mN in organ baths containing Krebs solution (36 °C) exposed to 95% O₂ and 5% CO₂. After 60-min incubation, a norepinephrine concentration-response (E/c) curve was generated to determine their half-maximal effecti...
The receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (cx). The model of RRM describes the... more
The receptorial responsiveness method (RRM) is a procedure that is based on a simple nonlinear regression while using a model with two variables (X, Y) and (at least) one parameter to be determined (cx). The model of RRM describes the co-action of two agonists that consume the same response capacity (due to the use of the same postreceptorial signaling in a biological system). While using RRM, uniquely, an acute increase in the concentration of an agonist (near the receptors) can be quantified (as cx), via evaluating E/c curves that were constructed with the same or another agonist in the same system. As this measurement is sensitive to the implementation of the curve fitting, the goal of the present study was to test RRM by combining different ways and setting options, namely: individual vs. global fitting, ordinary vs. robust fitting, and three weighting options (no weighting vs. weighting by 1/Y2 vs. weighting by 1/SD2). During the testing, RRM was used to estimate the known conc...
Protective effect of Cassia fistula fruit extract against bromobenzene-induced liver
hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin
Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women;... more
Advanced age is an independent risk factor for cardiovascular diseases, which might be further exacerbated by estrogen deficiency. Hormone replacement therapy (HRT) decreases cardiovascular risks and events in postmenopausal women; however, its effects are not fully elucidated in older individuals. Thus, the aim of our study is to examine the impact of HRT on oxidant/antioxidant homeostasis and cardiac remodeling. In our experiment, control (fertile) and aging (~20-month-old) female Wistar rats were used. Aging rats were further divided into estrogen- (E2, 0.1 mg/kg/day per os) or raloxifene- (RAL, 1.0 mg/kg/day per os) treated subgroups. After 2 weeks of treatment, cardiac heme oxygenase (HO) activity, total glutathione (GSH) content, matrix metalloproteinase-2 (MMP-2) activity, and the concentrations of collagen type I and tissue inhibitor of metalloproteinase (TIMP-2), as well as the infarct size, were determined. The aging process significantly decreased the antioxidant HO activ...
Background and Aims: Diabetic cardiomyopathy (DCM) is an emerging problem worldwide due to an increase in the incidence of type 2 diabetes. Animal studies have indicated that metformin and pioglitazone can prevent DCM partly by... more
Background and Aims: Diabetic cardiomyopathy (DCM) is an emerging problem worldwide due to an increase in the incidence of type 2 diabetes. Animal studies have indicated that metformin and pioglitazone can prevent DCM partly by normalizing insulin resistance, and partly by other, pleiotropic mechanisms. One clinical study has evidenced the insulin-senzitizing effect of the drug candidate BGP-15, along with additional animal studies that have confirmed its beneficial effects in models of diabetes, muscular dystrophy and heart failure, with the drug affecting chaperones, contractile proteins and mitochondria. Our aim was to investigate whether the inzulin-senzitizer BGP-15 exert any additive cardiovascular effects compared to metformin or pioglitazone, using Goto-Kakizaki (GotoK) rats. Methods: Rats were divided into five groups: (I) healthy control (Wistar), (II) diseased (GotoK), and GotoK rats treated with: (III) BGP-15, (IV) metformin, and (V) pioglitazone, respectively, for 12 we...
To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls. A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional,... more
To evaluate corneal parameters in patients with polymyositis (PM) and dermatomyositis (DM) and compare them with those of healthy controls. A total of 43 PM and 32 DM patients and 93 controls were enrolled in this cross-sectional, observational, case-control study. Corneal parameters were evaluated by Pentacam. Objective clinical tests of dry eye disease (DED) were also performed. All pachymetric measurements and corneal volumes (CVs) proved to be significantly lower both in PM and DM patients. The values of DM patients were closer to control values than those of the PM patients. For tear break-up time and Schirmer-I test values significant differences were observed between patients and controls, with values decreased both in PM and DM patients. PM patients rather than DM patients tend to develop thinner and low-volume corneas as compared to controls. Additionally, a high prevalence of DED among both PM and DM patients was also detected.
Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients. The study... more
Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients. The study included 32 SSc patients and 39 control subjects with no ocular symptoms or ocular surface disorders. All study participants underwent Pentacam evaluation and objective signs of dry eye disease (DED), and clinical parameters were evaluated. All pachymetric values, most of the corneal front surface, corneal volume, as well as anterior chamber depth measurements were significantly lower in the SSc group than in the control group (p < 0.05). Significant negative correlation was found between corneal parameters and age on the one hand, and disease duration on the other. Early recognition of corneal impairment, a possible extraintestinal manifestation of SSc, should be included in the check-up of the disease in order to reduce sight-threatening compli...
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on... more
Alzheimer's disease (AD) is a neurodegenerative disorder with cognitive impairment. Physical exercise has long been proven to be beneficial in the disorder. The present study was designed to examine the effect of voluntary exercise on spatial memory, imaging, and pathological abnormalities. Particular focus has been given to the role of heme oxygenase-1 (HO-1)-an important cellular cytoprotectant in preserving mental acuity-using an aging rat model of dementia. Male and female Wistar rats were segregated into six groups-namely, (i) aged sedentary (control) females (ASF, = 8); (ii) aged sedentary (control) males (ASM, = 8); (iii) aged running females (ARF, = 8); (iv) aged running males (ARM, = 8); (v) young control females (YCF, = 8); and (vi) young control males (YCM, = 8). Rats in the ARF and ARM groups had free access to a standardized inbuilt running wheel during the 3-month evaluation period. Spatial memory was investigated using the Morris Water Test, imaging and pathologic...
In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to... more
In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis. Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease or alleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacy and minimal toxicity of ...
We compared killing activity of micafungin in time-kill experiments in RPMI-1640 with and without 50% serum against Candida albicans, Candida dubliniensis and Candida africana reference strains and clinical isolates. Killing rates (k... more
We compared killing activity of micafungin in time-kill experiments in RPMI-1640 with and without 50% serum against Candida albicans, Candida dubliniensis and Candida africana reference strains and clinical isolates. Killing rates (k values) were determined for each strain and concentration. In RPMI-1640 MIC ranges were 0.015-0.03, 0.015-0.03 and 0.015 mg/L against C. albicans, C. dubliniensis and C. africana, respectively. In 50% serum MIC values for the three species increased 16- to 64-fold. In RPMI-1640 micafungin was fungicidal against two of three C. albicans isolates at 16 and 32 mg/L within 14.54 h and fungistatic against all C. africana and C. dubliniensis. Fifty per cent serum significantly decreased the growth rate of C. africana, but not of the other two species; weak in vivo replication ability of C. africana was confirmed in murine model. In 50% serum micafungin at 0.25 and 1 mg/L did not inhibit any of the three species (k values were always negative). Micafungin kill...

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Hypothesis. The present study evaluates the hypothesis that sour cherry seed extract (SCSE) protects against cardiovascular disease and inflammation in hypercholesterolemic rabbits, and that this protection correlates with SCSE-induced... more
Hypothesis. The present study evaluates the hypothesis that sour cherry seed extract (SCSE) protects against cardiovascular disease and inflammation in hypercholesterolemic rabbits, and that this protection correlates with SCSE-induced activity of heme oxygenase- 1 (HO-1), a cytoprotective enzyme contributing to oxidative stress responses.
Methods: 18 New Zealand white rabbits were divided into three groups receiving: I. cholesterol-free rabbit chow; II. chow containing 2% cholesterol; or III. 2% cholesterol plus SCSE for 16 weeks. Heart functions were monitored by echocardiography 0, 4, and 16 weeks after the initiation of cholesterol-supplemented feeding. At the 16-week time-point, isolated hearts were subjected to ischemia-reperfusion (I/R), followed by measurement of heart rate (HR), aortic flow (AF), coronary flow (CF), aortic pressure (AoP), and left ventricular developed pressure (LVDP). Myocardial infarct size was determined using triphenyl tetrazolium chloride (TTC). Quantification of fatty streaks was assessed using Sudan-III staining. Western blot analysis was used to determine the content of cytochrome c oxidase III (COX III), vascular endothelial growth factor (VEGF), and HO-1 in the myocardium.

Results: Relative to cholesterol-treated animals not receiving SCSE, SCSE-treated animals exhibited significantly improved cardiac function and improved peak early diastolic velocity to peak atrial velocity ratio (E'/A'), along with decreased atherosclerotic plaque formation and infarct size. Increased HO-1 and COX III protein expression and COX activity were also noted in hearts from SCSE-treated rabbits.

Conclusions: This study demonstrates SCSE cardioprotective effects on hypercholesterolemic hearts. Correlation of these outcomes with HO-1 expression suggests that the effect may be mediated by activity of this enzyme. However, definitive proof of HO-1 dependence requires further investigation.