BACKGROUND Despite all the technological progresses and conventional medical treatments, pain the... more BACKGROUND Despite all the technological progresses and conventional medical treatments, pain therapy remains a challenge for both children and adult patients. OBJECTIVE The aim of the study was to identify new transdermal Lidocaine delivery systems that will ensure a controlled release, an improved availability and will finally enhance local pain control. MATERIALS AND METHODS The experimental animals were adult Wistar rats weighing between 180-200 g. At the beginning of the experiments, we induced an inflammatory pain by administering λ-carrageenan, using a previously known model. Subsequently, the animals were subjected to a battery of nociception tests: algesimeter, cold plate and hot plate. Once the paw edema was obtained, the tested substance containing Lidocaine or eutectic mixture of local anesthetics (EMLA) cream was applied on the hind paw. Since we wanted to identify if our substance causes any local effect, the samples were collected from the paw, from the area where it ...
Cancer mortality and morbidity rates in children are significantly higher, even long after cessat... more Cancer mortality and morbidity rates in children are significantly higher, even long after cessation of treatment, than in the general population. Impaired renal function is one of the most severe observed late-effects after childhood cancer treatment. The current in depth review aims to underline the main features of the major drugs included in the chemotherapy regimens in children. For each of these drugs, we present the incidence and risk factors. The main pathophysiologic hypothesis of the drug nephrotoxicity, the clinical and biological features and the principal preventative and therapeutic methods are also presented. The associated comorbidities derived from nephrotoxicity are serious enough to consider the cancer prognosis as being unlikely optimistic. Further research is needed to provide less nephrotoxic drugs, to better identify renoprotective strategies and stratify the risk for nephrotoxicity.
2018 International Conference and Exposition on Electrical And Power Engineering (EPE), 2018
The achievements in the field of nanotechnology associated to THz/MRI medical imaging have signif... more The achievements in the field of nanotechnology associated to THz/MRI medical imaging have significantly enhanced the early detection of many pathological conditions. The paper intends to demonstrate an innovative test methodology based on clinical research with focus on Terahertz molecular imaging as advanced early-stage diagnostic method for gastric/digestive cancer, by use of an interdisciplinary approach in the field of nanomedicine, i.e. the development and use of tailored nanoparticles for enhancing specificity and increasing the resolution of the THz molecular imaging up to micro-meter scale.
Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of dru... more Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants we...
The mechanisms and nervous structures involved in visceral pain are poorly understood, although v... more The mechanisms and nervous structures involved in visceral pain are poorly understood, although visceral pain is one of the most debilitating clinical types of pain. We performed a literature review with the aim of identifying the distinct features of visceral pain and their potential use for identifying new therapeutic targets. In this article, we present the main structures involved in the generation and transmission of visceral pain, the main experimental techniques currently used for inducing and measuring visceral pain and the main mediators and receptors that play an essential role in this particular type of pain.
Experimental studies and clinical trials revealed the complex interconnections between imidazolin... more Experimental studies and clinical trials revealed the complex interconnections between imidazoline system and various other mediators such as epinephrine, norepinephrine; thus, explain their involvement in the pathophysiological mechanisms of different motor, behavioral and cognitive disturbances. In this study, we tested the influence induced by idazoxan and efaroxan on the cognitive performances in rats. Groups of 6 adult male Wistar rats were treated intraperitoneally according to the following protocol: group I (Control): distilled water 0.3 ml/100g; group II (IDZ): 3 mg/kg idazoxan and group III (EFR): 1 mg/kg efaroxan. The effects of the imidazoline receptor antagonists on the rats cognitive functions were assessed using the radial-arm maze, in order to count the time spent into the arms, the number of baited arms visited, but previously explored (working memory errors); the time taken to consume all baits and the number of entering in non-baited arms (reference memory errors)...
To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitam... more To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.
Pain continues to be a global unmet medical need, and the current recommendations for its managem... more Pain continues to be a global unmet medical need, and the current recommendations for its management require a constant exploration of new drugs that target multiple pain mechanisms, with an improved safety profile and increased treatment adherence. Currently, the enriched distribution and localization within nociceptors of the selective channel blockers and the critical role played by sodium channels in neuronal excitability nominate isoforms as specific targets to generate innovative compounds. In the present report, we verified the hypothesis that coadministration of Protoxin-II, a selective sodium channel inhibitor, and trace elements has direct and improved antinociceptive effects. Groups of seven Wistar rats were treated intracerebroventricularly with a combination of MgCl2, CdCl2, and ZnCl2and Protoxin-II, respectively, and with Protoxin-II alone (positive) or saline (negative) for controls. Evaluations were performed by nociception assay. Coadministration of these drugs caus...
The Terahertz’s wavelength is located between the microwave and the infrared region of the electr... more The Terahertz’s wavelength is located between the microwave and the infrared region of the electromagnetic spectrum. Because it is non-ionizing and non-invasive, Terahertz (THz)-based detection represents a very attractive tool for repeated assessments, patient monitoring, and follow-up. Cancer acts as the second leading cause of death in many regions, and current predictions estimate a continuous increasing trend. Of all types of tumors, digestive cancers represent an important percentage and their incidence is expected to increase more rapidly than other tumor types due to unhealthy lifestyle habits. Because it can precisely differentiate between different types of molecules, depending on water content, the information obtained through THz-based scanning could have several uses in the management of cancer patients and, more importantly, in the early detection of different solid tumors. The purpose of this manuscript is to offer a comprehensive overview of current data available on...
Alzheimer’s Disease affects approximately 33 million people worldwide and is characterized by pro... more Alzheimer’s Disease affects approximately 33 million people worldwide and is characterized by progressive loss of memory at the cognitive level. The formation of toxic amyloid oligomers, extracellular amyloid plaques and amyloid angiopathy in brain by amyloid beta peptides are considered a part of the identified mechanism involved in disease pathogenesis. The optimal treatment approach leads toward finding a chemical compound able to form a noncovalent complex with the amyloid peptide thus blocking the process of amyloid aggregation. This direction gained an increasing interest lately, many studies demonstrating that mass spectrometry is a valuable method useful for the identification and characterization of such molecules able to interact with amyloid peptides. In the present review we aim to identify in the scientific literature low molecular weight chemical compounds for which there is mass spectrometric evidence of noncovalent complex formation with amyloid peptides and also the...
Aging is an inevitable process in the human body that is associated with a multitude of systemic ... more Aging is an inevitable process in the human body that is associated with a multitude of systemic and localized changes. All these conditions have a common pathogenic mechanism characterized by the presence of a low-grade proinflammatory status. Inflammaging refers to all the processes that contribute to the occurrence of various diseases associated with aging such as frailty, atherosclerosis, Alzheimer’s disease, sarcopenia, type 2 diabetes, or osteoarthritis. Inflammaging is systemic, chronic, and asymptomatic. Osteoarthritis and many age-related degenerative joint diseases are correlated with aging mechanisms such as the presence of an inflammatory microenvironment and the impaired link between inflammasomes and autophagy. There is a close relationship between chondrocyte activity and local articular environment changes due to cell senescence, followed by secretion of inflammatory mediators. In addition, systemic inflammaging can lead to cartilage destruction, pain, disability, an...
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi
Methylene Blue (MB) can prevent electron leaking, increase mitochondrial oxidative phosphorylatio... more Methylene Blue (MB) can prevent electron leaking, increase mitochondrial oxidative phosphorylation, and reduce ROS overproduction under pathological conditions, currently being trace evidence that it can alter pain perception in humans by local administration during certain surgical procedures. Riboflavin or vitamin B2 (B2) constitutes a part of the vitamin B group, which in recent studies shows a growing implication in the treatment of some pathology that imply pain management. To investigate the effect of one dose of Riboflavin and Methylene Blue on nociception and visceral pain in mice. A total of 48 BALB/c male mice were divided into 3 groups: MB Group, B2 Group and C Group. MB (5 mg/kg b.w.), B2 (100 mg/kg b.w.) or an equivalent volume of saline was administered intraperitoneally. Mice were tested before (baseline) and after drugs administration over a 4h period. Nociception was evaluated by means of Hot Plate Test (HPT) and TFT (Tail Flick Test). Visceral pain was evaluated 2h...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
The present study aims to evaluate whether ascorbic acid (AA) and curcumin, two substances with r... more The present study aims to evaluate whether ascorbic acid (AA) and curcumin, two substances with redox properties, have similar effects on different models of pain in mice. This study included a total of 28 mice that were divided into four groups. One group (AA) received intraperitoneally 500 mg/kg b.w. AA for 21 days and the 2-nd group (curcumin) received 120 mg/kg b.w. curcumin by gastric gavage for two weeks. Other two groups serve as control and received vehicle in a dose--time manner similar to that of the treated groups. The pain models (oro-facial formalin induced pain, paw formalin induced pain and visceral pain) were performed 24 h after the last dose. When compared with control groups, curcumin significantly decreases pain perception in oro-facial (p = 0.01 1-st phase, p = 0.002 2-nd phase) and paw formalin induced pain (p = 0.04 1-st and 2-nd phase) while AA stimulates pain perception in acid acetic induced visceral pain (p = 0.05) and increases oro-facial inflammatory pai...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Rom... more Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Romania is not considered an endemic country and there are only few reports of sporadic cases in the last 100 years. However, studies suggest that the disease is spreading north. We present the case of a 44 year old female that presented with asthenia, perspirations, vertigo, weight loss and menometrorhagias in small to medium quantity. Clinical exam revealed the presence of splenomegaly and her blood tests indicated she had pancitopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections that evolve with spleen enlargement, autoimmune-related splenomegaly and hepatic--all tests were negative. She refused the bone marrow aspiration. Three months later, her condition worsened and the menometrorragias became more severe. Bone marrow aspiration revealed the presence of numerous intra and extracellular Leishmania spp. amastigotes. A detailed anamnesi...
BACKGROUND Despite all the technological progresses and conventional medical treatments, pain the... more BACKGROUND Despite all the technological progresses and conventional medical treatments, pain therapy remains a challenge for both children and adult patients. OBJECTIVE The aim of the study was to identify new transdermal Lidocaine delivery systems that will ensure a controlled release, an improved availability and will finally enhance local pain control. MATERIALS AND METHODS The experimental animals were adult Wistar rats weighing between 180-200 g. At the beginning of the experiments, we induced an inflammatory pain by administering λ-carrageenan, using a previously known model. Subsequently, the animals were subjected to a battery of nociception tests: algesimeter, cold plate and hot plate. Once the paw edema was obtained, the tested substance containing Lidocaine or eutectic mixture of local anesthetics (EMLA) cream was applied on the hind paw. Since we wanted to identify if our substance causes any local effect, the samples were collected from the paw, from the area where it ...
Cancer mortality and morbidity rates in children are significantly higher, even long after cessat... more Cancer mortality and morbidity rates in children are significantly higher, even long after cessation of treatment, than in the general population. Impaired renal function is one of the most severe observed late-effects after childhood cancer treatment. The current in depth review aims to underline the main features of the major drugs included in the chemotherapy regimens in children. For each of these drugs, we present the incidence and risk factors. The main pathophysiologic hypothesis of the drug nephrotoxicity, the clinical and biological features and the principal preventative and therapeutic methods are also presented. The associated comorbidities derived from nephrotoxicity are serious enough to consider the cancer prognosis as being unlikely optimistic. Further research is needed to provide less nephrotoxic drugs, to better identify renoprotective strategies and stratify the risk for nephrotoxicity.
2018 International Conference and Exposition on Electrical And Power Engineering (EPE), 2018
The achievements in the field of nanotechnology associated to THz/MRI medical imaging have signif... more The achievements in the field of nanotechnology associated to THz/MRI medical imaging have significantly enhanced the early detection of many pathological conditions. The paper intends to demonstrate an innovative test methodology based on clinical research with focus on Terahertz molecular imaging as advanced early-stage diagnostic method for gastric/digestive cancer, by use of an interdisciplinary approach in the field of nanomedicine, i.e. the development and use of tailored nanoparticles for enhancing specificity and increasing the resolution of the THz molecular imaging up to micro-meter scale.
Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of dru... more Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants we...
The mechanisms and nervous structures involved in visceral pain are poorly understood, although v... more The mechanisms and nervous structures involved in visceral pain are poorly understood, although visceral pain is one of the most debilitating clinical types of pain. We performed a literature review with the aim of identifying the distinct features of visceral pain and their potential use for identifying new therapeutic targets. In this article, we present the main structures involved in the generation and transmission of visceral pain, the main experimental techniques currently used for inducing and measuring visceral pain and the main mediators and receptors that play an essential role in this particular type of pain.
Experimental studies and clinical trials revealed the complex interconnections between imidazolin... more Experimental studies and clinical trials revealed the complex interconnections between imidazoline system and various other mediators such as epinephrine, norepinephrine; thus, explain their involvement in the pathophysiological mechanisms of different motor, behavioral and cognitive disturbances. In this study, we tested the influence induced by idazoxan and efaroxan on the cognitive performances in rats. Groups of 6 adult male Wistar rats were treated intraperitoneally according to the following protocol: group I (Control): distilled water 0.3 ml/100g; group II (IDZ): 3 mg/kg idazoxan and group III (EFR): 1 mg/kg efaroxan. The effects of the imidazoline receptor antagonists on the rats cognitive functions were assessed using the radial-arm maze, in order to count the time spent into the arms, the number of baited arms visited, but previously explored (working memory errors); the time taken to consume all baits and the number of entering in non-baited arms (reference memory errors)...
To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitam... more To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.
Pain continues to be a global unmet medical need, and the current recommendations for its managem... more Pain continues to be a global unmet medical need, and the current recommendations for its management require a constant exploration of new drugs that target multiple pain mechanisms, with an improved safety profile and increased treatment adherence. Currently, the enriched distribution and localization within nociceptors of the selective channel blockers and the critical role played by sodium channels in neuronal excitability nominate isoforms as specific targets to generate innovative compounds. In the present report, we verified the hypothesis that coadministration of Protoxin-II, a selective sodium channel inhibitor, and trace elements has direct and improved antinociceptive effects. Groups of seven Wistar rats were treated intracerebroventricularly with a combination of MgCl2, CdCl2, and ZnCl2and Protoxin-II, respectively, and with Protoxin-II alone (positive) or saline (negative) for controls. Evaluations were performed by nociception assay. Coadministration of these drugs caus...
The Terahertz’s wavelength is located between the microwave and the infrared region of the electr... more The Terahertz’s wavelength is located between the microwave and the infrared region of the electromagnetic spectrum. Because it is non-ionizing and non-invasive, Terahertz (THz)-based detection represents a very attractive tool for repeated assessments, patient monitoring, and follow-up. Cancer acts as the second leading cause of death in many regions, and current predictions estimate a continuous increasing trend. Of all types of tumors, digestive cancers represent an important percentage and their incidence is expected to increase more rapidly than other tumor types due to unhealthy lifestyle habits. Because it can precisely differentiate between different types of molecules, depending on water content, the information obtained through THz-based scanning could have several uses in the management of cancer patients and, more importantly, in the early detection of different solid tumors. The purpose of this manuscript is to offer a comprehensive overview of current data available on...
Alzheimer’s Disease affects approximately 33 million people worldwide and is characterized by pro... more Alzheimer’s Disease affects approximately 33 million people worldwide and is characterized by progressive loss of memory at the cognitive level. The formation of toxic amyloid oligomers, extracellular amyloid plaques and amyloid angiopathy in brain by amyloid beta peptides are considered a part of the identified mechanism involved in disease pathogenesis. The optimal treatment approach leads toward finding a chemical compound able to form a noncovalent complex with the amyloid peptide thus blocking the process of amyloid aggregation. This direction gained an increasing interest lately, many studies demonstrating that mass spectrometry is a valuable method useful for the identification and characterization of such molecules able to interact with amyloid peptides. In the present review we aim to identify in the scientific literature low molecular weight chemical compounds for which there is mass spectrometric evidence of noncovalent complex formation with amyloid peptides and also the...
Aging is an inevitable process in the human body that is associated with a multitude of systemic ... more Aging is an inevitable process in the human body that is associated with a multitude of systemic and localized changes. All these conditions have a common pathogenic mechanism characterized by the presence of a low-grade proinflammatory status. Inflammaging refers to all the processes that contribute to the occurrence of various diseases associated with aging such as frailty, atherosclerosis, Alzheimer’s disease, sarcopenia, type 2 diabetes, or osteoarthritis. Inflammaging is systemic, chronic, and asymptomatic. Osteoarthritis and many age-related degenerative joint diseases are correlated with aging mechanisms such as the presence of an inflammatory microenvironment and the impaired link between inflammasomes and autophagy. There is a close relationship between chondrocyte activity and local articular environment changes due to cell senescence, followed by secretion of inflammatory mediators. In addition, systemic inflammaging can lead to cartilage destruction, pain, disability, an...
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi
Methylene Blue (MB) can prevent electron leaking, increase mitochondrial oxidative phosphorylatio... more Methylene Blue (MB) can prevent electron leaking, increase mitochondrial oxidative phosphorylation, and reduce ROS overproduction under pathological conditions, currently being trace evidence that it can alter pain perception in humans by local administration during certain surgical procedures. Riboflavin or vitamin B2 (B2) constitutes a part of the vitamin B group, which in recent studies shows a growing implication in the treatment of some pathology that imply pain management. To investigate the effect of one dose of Riboflavin and Methylene Blue on nociception and visceral pain in mice. A total of 48 BALB/c male mice were divided into 3 groups: MB Group, B2 Group and C Group. MB (5 mg/kg b.w.), B2 (100 mg/kg b.w.) or an equivalent volume of saline was administered intraperitoneally. Mice were tested before (baseline) and after drugs administration over a 4h period. Nociception was evaluated by means of Hot Plate Test (HPT) and TFT (Tail Flick Test). Visceral pain was evaluated 2h...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
The present study aims to evaluate whether ascorbic acid (AA) and curcumin, two substances with r... more The present study aims to evaluate whether ascorbic acid (AA) and curcumin, two substances with redox properties, have similar effects on different models of pain in mice. This study included a total of 28 mice that were divided into four groups. One group (AA) received intraperitoneally 500 mg/kg b.w. AA for 21 days and the 2-nd group (curcumin) received 120 mg/kg b.w. curcumin by gastric gavage for two weeks. Other two groups serve as control and received vehicle in a dose--time manner similar to that of the treated groups. The pain models (oro-facial formalin induced pain, paw formalin induced pain and visceral pain) were performed 24 h after the last dose. When compared with control groups, curcumin significantly decreases pain perception in oro-facial (p = 0.01 1-st phase, p = 0.002 2-nd phase) and paw formalin induced pain (p = 0.04 1-st and 2-nd phase) while AA stimulates pain perception in acid acetic induced visceral pain (p = 0.05) and increases oro-facial inflammatory pai...
Revista medico-chirurgicală̆ a Societă̆ţ̜ii de Medici ş̧i Naturaliş̧ti din Iaş̧i
Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Rom... more Leishmaniasis is a parasitic infection caused by protozoans classified as Leishmania species. Romania is not considered an endemic country and there are only few reports of sporadic cases in the last 100 years. However, studies suggest that the disease is spreading north. We present the case of a 44 year old female that presented with asthenia, perspirations, vertigo, weight loss and menometrorhagias in small to medium quantity. Clinical exam revealed the presence of splenomegaly and her blood tests indicated she had pancitopenia; differential diagnosis included myeloproliferative or lymphoproliferative disorders, infections that evolve with spleen enlargement, autoimmune-related splenomegaly and hepatic--all tests were negative. She refused the bone marrow aspiration. Three months later, her condition worsened and the menometrorragias became more severe. Bone marrow aspiration revealed the presence of numerous intra and extracellular Leishmania spp. amastigotes. A detailed anamnesi...
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