RESUMO
Diabetes mellitus (DM) is a chronic illness with an increasing global prevalence. More than 537 million cases of diabetes were reported worldwide in 2021, and the number is steadily increasing. The worldwide number of people suffering from DM is projected to reach 783 million in 2045. In 2021 alone, more than USD 966 billion was spent on the management of DM. Reduced physical activity due to urbanization is believed to be the major cause of the increase in the incidence of the disease, as it is associated with higher rates of obesity. Diabetes poses a risk for chronic complications such as nephropathy, angiopathy, neuropathy and retinopathy. Hence, the successful management of blood glucose is the cornerstone of DM therapy. The effective management of the hyperglycemia associated with type 2 diabetes includes physical exercise, diet and therapeutic interventions (insulin, biguanides, second generation sulfonylureas, glucagon-like peptide 1 agonists, dipeptidyl-peptidase 4 inhibitors, thiazolidinediones, amylin mimetics, meglitinides, α-glucosidase inhibitors, sodium-glucose cotransporter-2 inhibitors and bile acid sequestrants). The optimal and timely treatment of DM improves the quality of life and reduces the severe burden of the disease for patients. Genetic testing, examining the roles of different genes involved in the pathogenesis of DM, may also help to achieve optimal DM management in the future by reducing the incidence of DM and by enhancing the use of individualized treatment regimens.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Qualidade de Vida , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores da Dipeptidil Peptidase IV/farmacologia , Inibidores da Dipeptidil Peptidase IV/uso terapêuticoRESUMO
Allium species, belonging to Alliaceae family, are among the oldest cultivated vegetables used as food. Garlic, onions, leeks and chives, which belong to this family, have been reported to have medicinal properties. The Allium species constituents have been shown to have antibacterial and antioxidant activities, and, in addition, other biological properties. These activities are related to their rich organosulfur compounds. These organosulfur compounds are believed to prevent the development of cancer, cardiovascular, neurological, diabetes, liver diseases as well as allergy and arthritis. There have also been reports on toxicities of these compounds. The major active compounds of Allium species includes, diallyl disulfide, diallyl trisulfide, diallyl sulfide, dipropyl disulfide, dipropyl trisulfide, 1-propenylpropyl disulfide, allyl methyl disulfide and dimethyl disulfide. The aim of this review is to focus on a variety of experimental and clinical reports on the effectiveness, toxicities and possible mechanisms of actions of the active compounds of garlic, onions, leek and chives.
Assuntos
Allium/química , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus/tratamento farmacológico , Neoplasias/tratamento farmacológico , Plantas Medicinais/química , Allium/metabolismo , Animais , Anti-Infecciosos/química , Antioxidantes/química , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Plantas Medicinais/metabolismoRESUMO
Our aim was to find chlorine-substituted antidotes against organophosphate poisoning and compare their pharmacokinetics to their parent compound, K-203. White male Wistar rats were intramuscularly injected with K-203, K-867 or K-870. Serum, brain, kidneys, liver, lung, eyes, and testes tissues were taken after 5, 15, 30, 60, and 120 min and analyzed using reversed-phase high-performance liquid chromatography. K-203, K-867, or K-870 was present in every tissue that was analyzed, including the serum, the eyes, testes, liver, kidneys, lungs, and the brain. The serum levels of K-867 and K-870 (chlorine-substituted derivatives of K-203) were nearly constant between 15 and 30 min, while their parent compound (K-203) showed peak level at 15 min after the administration of 30 µmol/rat. Neither K-203, nor K-867 or K-870 were toxic at a dose of 100 µmol/200 g in rats. Chlorine-substitution of K-867 and K-870 produced limited absorbance and distribution compared to their parent compound, K203.
Assuntos
Antídotos/metabolismo , Butirilcolinesterase/metabolismo , Intoxicação por Organofosfatos/tratamento farmacológico , Oximas/farmacocinética , Compostos de Piridínio/farmacocinética , Animais , Cloro , Masculino , Ratos , Ratos WistarRESUMO
Nociceptin (NC), also known as Orphanin FQ, is a brain peptide involved in the regulation of pain, but its role in the endocrine pancreas is poorly understood. The present study examines the pattern of distribution of NC and its effect on insulin and glucagon secretion after the onset of diabetes mellitus (DM). Male Wistar rats weighing 150-200 g were made diabetic with streptozotocin (60 mg/kg body weight, intraperitoneally). Four weeks after the induction of DM, pancreatic tissues were retrieved and processed for immunofluorescence, immunoelectron microscopy, and insulin and glucagon secretion. Isolated islets from non-diabetic and diabetic rats were used to determine the effect of NC on insulin release. NC was discerned in islet cells of non-diabetic control and diabetic rat pancreata. NC co-localized only with insulin in pancreatic beta cells. NC did not co-localize with either glucagon or somatostatin or pancreatic polypeptide. The number of NC-positive cells was markedly (p < 0.001) reduced after the onset of DM. Electron microscopy study showed that NC is located with insulin in the same secretory granules of the beta cells of both non-diabetic and diabetic rat pancreas. NC inhibits insulin release markedly (p < 0.05) from pancreatic tissue fragments of non-diabetic and diabetic rats. In contrast, NC at 10-12 M stimulates insulin release in isolated islets of DM rats. In conclusion, NC co-localizes with insulin only in the islet of Langerhans. The co-localization of NC with insulin suggests a role for NC in the regulation of pancreatic beta cell function.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Secreção de Insulina , Peptídeos Opioides/metabolismo , Pâncreas/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Glucagon/metabolismo , Insulina/metabolismo , Masculino , Modelos Biológicos , Peptídeos Opioides/farmacologia , Pâncreas/ultraestrutura , Polipeptídeo Pancreático/metabolismo , Ratos Wistar , Somatostatina/metabolismo , NociceptinaRESUMO
Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing. Two novel oximes (K378 and K727) were investigated in silico and in vitro and compared with an experimental oxime (kamiloxime; K-27) and pralidoxime. In silico the molecular interactions between AChE and oximes were examined and binding energies were assessed. LogP (predicted log of the octanol/water partition coefficient) was estimated. In vitro the intrinsic ability of the oximes to inhibit AChE (IC50) and their reactivation potency (R50) when used in paraoxon inhibited human RBC-AChE was determined. Molecular docking revealed that K378 and K727 bind to the peripheral site(s) with high binding energies in contrast to the central binding of K-27 and pralidoxime. LogP values indicating that the novel compounds are significantly less hydrophilic than K-27 or pralidoxime. IC50 of K378 and K727 were comparable (0.9 and 1 µM, respectively) but orders of magnitude lower than comparators. R50 values revealed their inability to reactivate paraoxon inhibited AChE. It is concluded that the novel oximes K378 and K727 are unlikely to be clinically useful. The in silico and in vitro studies described allow avoidance of unnecessary in vivo animal work and contribute to the reduction of laboratory animal use.
Assuntos
Antídotos/farmacologia , Inibidores da Colinesterase/toxicidade , Reativadores da Colinesterase/farmacologia , Simulação de Acoplamento Molecular , Intoxicação por Organofosfatos/tratamento farmacológico , Oximas/farmacologia , Paraoxon/análogos & derivados , Compostos de Pralidoxima/farmacologia , Compostos de Piridínio/farmacologia , Acetilcolinesterase/sangue , Acetilcolinesterase/química , Antídotos/química , Antídotos/metabolismo , Sítios de Ligação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/metabolismo , Reativadores da Colinesterase/química , Reativadores da Colinesterase/metabolismo , Relação Dose-Resposta a Droga , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/química , Humanos , Masculino , Intoxicação por Organofosfatos/sangue , Intoxicação por Organofosfatos/enzimologia , Oximas/química , Oximas/metabolismo , Paraoxon/química , Paraoxon/metabolismo , Paraoxon/toxicidade , Compostos de Pralidoxima/química , Compostos de Pralidoxima/metabolismo , Ligação Proteica , Conformação Proteica , Compostos de Piridínio/química , Compostos de Piridínio/metabolismo , Relação Estrutura-AtividadeRESUMO
There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure.
Assuntos
Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Paraoxon/toxicidade , Praguicidas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Masculino , Microscopia Eletrônica , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Estreptozocina , Testes de Toxicidade SubcrônicaRESUMO
Clinical effect of drugs is influenced by the composition of the pharmaceutical preparation but substantially by the fate of the drug in the body. Metabolism of the xenobiotic drug compounds may result in pharmacologically inactive metabolites, however, metabolites with higher pharmacological activity can also be produced. These active metabolites may have different pharmacokinetic properties than the parent drug. Co-existence of the parent drug and the active metabolite in the body may significantly modify the therapeutic effect. Knowledge-based system of pharmacokinetics and metabolism of the drugs has a high impact in understanding both the pharmacokinetic and the pharmacodynamic interactions. Cytochrome P450 isoenzymes taking part in the metabolic activity of the central nervous system is a developing area in metabolic studies. In the present study CYP isoenzymes with significant activity in the brain and the clinically important pharmacokinetic and metabolic data of antidepressive compounds are summarized.
Assuntos
Antidepressivos/metabolismo , Antidepressivos/farmacocinética , Encéfalo/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Pró-Fármacos , Antidepressivos/sangue , Encéfalo/enzimologia , Interações Medicamentosas , HumanosRESUMO
Nociceptin (NC) consists of 17 amino acids (aa) and takes part in the processing of learning and memory. The role of NC in the induction of endogenous antioxidants in still unclear. We examined the effect of NC on the expression of endogenous antioxidants in kidney, liver, cerebral cortex (CC), and hippocampus after the onset of diabetes mellitus, using enzyme-linked immunosorbent assay and immunohistochemistry. Exogenous NC (aa chain 1-17; 10 µg/kg body weight) was given intraperitoneally to normal and diabetic rats for 5 days. Our results showed that catalase (CAT) is present in the proximal (PCT) and distal (DCT) convoluted tubules of kidney, hepatocytes, and neurons of CC and hippocampus. The expression of CAT was significantly (p < 0.05) reduced in the kidney of normal and diabetic rats after treatment with NC. However, NC markedly (p < 0.001) increased the expression CAT in the liver and neurons of CC of diabetic rats. Superoxide dismutase (SOD) is widely distributed in the PCT and DCT of kidney, hepatocytes, and neurons of CC and hippocampus. NC significantly (p < 0.001) increased the expression of SOD in hepatocytes and neurons of CC and the hippocampus but not in the kidney. Glutathione reductase (GRED) was observed in kidney tubules, hepatocytes and neurons of the brain. NC markedly increased (p < 0.001) the expression of GRED in PCT and DCT cells of the kidney and hepatocytes of liver and neurons of CC. In conclusion, NC is a strong inducer of CAT, SOD, and GRED expression in the kidney, liver and brain of diabetic rats.
RESUMO
The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.
Assuntos
Acetilcolinesterase/química , Canabinoides/farmacologia , Inibidores da Colinesterase/farmacologia , Abuso de Maconha/genética , Polimorfismo de Nucleotídeo Único , Receptor CB1 de Canabinoide/genética , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Sítios de Ligação , Canabinoides/química , Inibidores da Colinesterase/química , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Simulação de Acoplamento Molecular , Ligação ProteicaRESUMO
Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The reactivation of these inhibited enzymes is paramount for their normal function. Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (POX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM). In vitro studies showed higher intrinsic toxicities of both oximes than 2-PAM for AChE. No substantial reactivation of hBChE was noted by tested concentration. Contrary to 2-PAM, the in silico study predicted lower binding free energies for both oximes. However, the detailed interaction study revealed inability of oximes to interact with catalytic anionic site of AChE and hBChE in contrast to 2-PAM. Both in vitro and in silico studies conclude that K456 and K733 are unlikely to be used as reactivators of paraoxon-inhibited AChE or BChE.
Assuntos
Inibidores da Colinesterase/farmacologia , Reativadores da Colinesterase/farmacologia , Oximas/farmacologia , Paraoxon/antagonistas & inibidores , Compostos de Piridínio/farmacologia , Acetilcolinesterase/química , Butirilcolinesterase/química , Eritrócitos/enzimologia , Humanos , Paraoxon/farmacologiaRESUMO
Introduction: More than 424 million adults have diabetes mellitus (DM). This number is expected to increase to 626 million by 2045. The majority (90-95%) of people with DM has type 2-diabetes (T2DM). The continued prevalence of DM and associated complications has prompted investigators to find new therapies. One of the most recent additions to the anti-diabetic armamentarium are inhibitors of sodium-glucose co-transporters 1 and 2 (SGLT1, SGLT2). Areas covered: The authors review the status of SGLT2 inhibitors for the treatment of T2DM and place an emphasis on those agents in early phase clinical trials. Data and information were retrieved from American Diabetes Association, Diabetes UK, ClinicalTrials.gov, PubMed, and Scopus websites. The keywords used in the search were T2DM, SGLT1, SGLT2, and clinical trials. Expert opinion: The benefits of SGLT inhibitors include reductions in serum glycated hemoglobin (HbA1c), body weight, blood pressure and cardiovascular and renal events. However, SGLT inhibitors increase the risk of genitourinary tract infections, diabetic ketoacidosis, and bone fractures. The development of SGLT inhibitors with fewer side effects and as combination therapies are the key to maximizing the therapeutic effects of this important class of anti-diabetic drug.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Transportador 1 de Glucose-Sódio/antagonistas & inibidores , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Adulto , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Desenvolvimento de Medicamentos/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacologia , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
Introduction: Currently, 424 million people aged between 20 and 79 years worldwide are diabetic. More than 25% of adults aged over 65 years in North America have Type 2 diabetes mellitus (DM). Diabetes-induced osteoporosis (DM-OS) is caused by chronic hyperglycemia, advanced glycated end products and oxidative stress. The increase in the prevalence of DM-OS has prompted researchers to develop new biological therapies for the management of DM-OS. Areas covered: This review covered the current and novel biological agents used in the management of DM-OS. Data were retrieved from PubMed, Scopus, American Diabetes Association and International Osteoporosis Foundation websites, and ClinicalTrials.gov. The keywords for the search included: DM, osteoporosis, and management. Expert opinion: Several biological molecules have been examined in order to find efficient drugs for the treatment of DM-OS. These biological agents include anti-osteoporosis drugs: net anabolics (parathyroid hormone/analogs, androgens, calcilytics, anti-sclerostin antibody), net anti-resorptive osteoporosis drugs (calcitonin, estrogen, selective estrogen receptor modulators, bisphosphonates, RANKL antibody) and anti-diabetic drugs (alpha glucosidase inhibitors, sulfonylureas, biguanides, meglitinides, thiazolidinediones, GLP-1 receptor agonists, dipeptidylpeptidase-4 inhibitors, sodium glucose co-transporter-2 inhibitors, insulin). Biological medications that effectively decrease hyperglycemia and, at the same time, maintain bone health would be an ideal drug/drug combination for the treatment of DM-OS.
Assuntos
Produtos Biológicos/uso terapêutico , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Osteoporose/tratamento farmacológico , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Osteoporose/etiologiaRESUMO
Biosensors using cholinesterases as the biorecognition component have been used to assay organophosphates and carbamates for a long time. In this review, some strategies convenient for biosensor construction are presented. Solutions for cholinesterase immobilization and output signal monitoring are presented as the basic presumptions for successful biosensor construction.
Assuntos
Técnicas Biossensoriais/métodos , Colinesterases/metabolismo , Animais , Enzimas Imobilizadas/metabolismoRESUMO
INTRODUCTION: Tinuvin 770 [bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate, Ciba-Geigy, Basel, Switzerland] is a UV light stabilizer that is a component of many plastic materials used world-wide in the medical and food industries. We report on the acute hemodynamic effects of Tinuvin 770 examined in dogs. MATERIALS AND METHODS: Tinuvin 770 was dissolved in a mixture of saline and ethanol (1:1 v/v) and was administered to 12 intravenously narcotized and respirated dogs in increasing doses (T1-T7: 1, 3.3, 6.6, 10, 33.3, 66.6 and 100 mg, respectively). The doses were given as bolus injections over a three minute period, and the effects were recorded for 12 minutes. The vehicle was used as a control. Hemodynamic parameters (heart rate, blood pressure, end-diastolic pressure, dp/dt, cardiac output) and ECG were monitored continously. RESULTS: At doses T1-T4, systolic and diastolic blood pressures, mean pressure and ventricular contractility were significantly decreased without significant changes in cardiac output, heart rate, or PQ interval. At doses T5 and T6, declines in blood pressure and myocardial contractility were observed. At doses T6 and T7, heart rate and PQ interval decreased substantially. Irreversible circulatory failure occured in one dog after administering dose T6 and in 8 dogs following dose T7. CONCLUSION: Tinuvin 770 induces acute hemodynamic alterations. In lower doses, it causes peripheral vasodilatation, however at higher doses acute cardiac failure occured. Plastics containing Tinuvin 770 should be used with care in medical practice and the laboratory.
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BACKGROUND: A large number of classical and recently discovered plants are indicated in preventing and/or treating Alzheimer's disease (AD). OBJECTIVE: Name of plants with their anti-AD effects are important for their further use and investigation. METHOD: A short overview of AD is given; anti-Alzheimer plants are given in a Table. RESULTS: Various medicinal plants are listed here as sources of popular medicines to be used in cases when patients are afraid of developing and/or suffer from AD. Some of these plants have been used for centuries. The major sources in the literature, over one hundred of references are given for plants that show beneficial effect on the progress of AD. CONCLUSION: Plant extracts are widely used addition to the synthetic drugs approved by various administrative authorities to stop/slow down the progress of symptoms of AD.
RESUMO
K-27 is a bisquaternary asymmetric pyridinium aldoxime-type cholinesterase reactivator of use in the treatment of poisoning with organophosphorous esterase inhibitors. A sensitive, simple and reliable reverse-phase high-performance liquid chromatographic method with electrochemical detection was developed for the measurement of K-27 concentrations in rat brain, cerebrospinal fluid, serum and urine samples. Male Wistar rats were treated intramuscularly with K-27 and the samples were collected 60 min later. Separation was carried out on an octadecyl silica stationary phase and a disodium phosphate solution (pH 3.7) containing citric acid, octane sulphonic acid and acetonitrile served as mobile phase. Measurements were carried out at 30 degrees C at E(ox) 0.65 V. The calibration curve was linear through the range of 10-250 ng/mL. Accuracy, precision and the limit of detection calculated were satisfactory according to internationally accepted criteria. Limit of quantitation was 10 ng/mL. The method developed is reliable and sensitive enough for monitoring K-27 levels from different biological samples including as little as 10 microL of cerebrospinal fluid. The method--with slight modification in the composition of the mobile phase--can be used to measure a wide range of other related pyridinium aldoxime-type cholinesterase reactivators.
Assuntos
Reativadores da Colinesterase/análise , Cromatografia Líquida de Alta Pressão/métodos , Eletroquímica/métodos , Oximas/análise , Compostos de Piridínio/análise , Animais , Calibragem , Masculino , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Several studies suggested a possible link between substance use disorder and attention deficit hyperactivity syndrome (ADHD). The ADHD Rating Scale (ADHD-RS) completed by parents is a tool for diagnosing ADHD in childhood. We adapted this questionnaire for a self-report retrospective scale to estimate the presence of childhood ADHD symptoms in adults. This retrospective questionnaire was completed by 121 heroin dependent patients and 85 age- and sex-matched healthy controls. The ADHD Rating Scale Retrospective Questionnaire is a novel tool for assessing ADHD symptoms that demonstrated high validity. Our results showed strong gender difference in the prevalence of ADHD symptoms, since male subjects obtained higher mean scores of both attention-deficit and hyperactivity scales than females in both the control and the heroin dependent population. Besides, mean score of both scales were higher in the clinical population as a higher portion of substance abusers reported symptoms of childhood ADHD than controls. These results support the hypothesis that untreated childhood ADHD could be a risk factor for developing substance use disorder.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/complicações , Dependência de Heroína/etiologia , Inquéritos e Questionários , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Feminino , Dependência de Heroína/psicologia , Humanos , Masculino , Estudos Retrospectivos , Fatores Sexuais , Inquéritos e Questionários/normasRESUMO
INTRODUCTION: Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 350 million people worldwide. Also, another one billion people in the world are pre-diabetic, who may eventually end up with full- blown diabetes. It costs around 1,200 billion USD to diagnose, treat and care for both type 1 DM (T1DM) and type 2 DM (T2DM) patients globally. The disorder is rapidly increasing out of proportion in both developed and developing countries, especially T2DM, which is associated with modern lifestyle habits such as reduced physical activity, diet, obesity and genetic factors. If left untreated, DM can lead to a number of diseases and long-term complications leading subsequently to death. Areas Covered: In this mini review, we aim to highlight a number of complications, cascades or pathways (polyol, hexosamine, protein kinase C, advanced glycation-end product) of events and cellular, sub-cellular and molecular mechanisms associated with DM-induced hyperglycaemia (HG). CONCLUSION: Chronic complications of DM are caused largely by HG-induced cellular and molecular impairment of neural and vascular structure and function. HG-induced oxidative stress is a major contributor in the development of long-term complications of DM. DM-induced neuropathy and angiopathy, in turn, may lead to the dysfunction of cells, tissues and organ systems.
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Complicações do Diabetes/fisiopatologia , Hiperglicemia/fisiopatologia , Complicações do Diabetes/epidemiologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Estresse Oxidativo , Fatores de RiscoRESUMO
INTRODUCTION: The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation. The increase in the prevalence of DFU has prompted researchers to find new therapies for the management of DFU. Areas covered: This review presents the current status of novel biological therapies used in the treatment of DFU. Literature information and data analysis were collected from PubMed, the website of the American Diabetes Association, and ClinicalTrials.gov. The keywords used in the search were: DM, DFU, complications of DM. Expert opinion: Many biological agents have been investigated in a bid to find an effective therapy for DFU. These include growth factors (platelet-derived growth factor, vascular endothelial growth factor etc), stem cells (epithelial progenitor-, adipose-derived stem cells etc), anti-diabetic drugs (insulin, exendin-4), herbs, urokinase, dalteparin, statins and bio-agents such as acid peptide matrix. Biological agents that can reduce hyperglycaemia, increase sensation, microcirculation and oxygenation and repair lost tissue are the most ideal for the treatment of DFU.
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Pé Diabético/terapia , Produtos Biológicos/uso terapêutico , Pé Diabético/tratamento farmacológico , Pé Diabético/etiologia , Neuropatias Diabéticas/complicações , Humanos , Hipoglicemiantes/uso terapêutico , Imunomodulação , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Transplante de Células-Tronco , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , CicatrizaçãoRESUMO
BACKGROUND: Selegiline [(-)-deprenyl] is widely used for the treatment of Parkinson's disease in humans. OBJECTIVE: Time-dependence of tissue distribution of selegiline following per os administration to rats. METHOD: Oral administration of radiolabeled selegiline to rats resulted in a pattern of tissue distribution similar to that following intraperitoneal injection. Analyses were done using both reversed-phase HPLC and also by counting radioactivity in various body compartments of rats. RESULTS: As a consequence of oral administration of 30 mg/kg of selegiline, its level in the stomach was extremely high (179.57 µg/g tissue through 54.67 µg/g at 15 min to 120 min), that is one magnitude higher than that in the serum level. High selegiline concentrations were also detected in the lacrimal glands (7.45 µg/g), kidneys (6.87 µg/g), livers (6.01 µg/g) and lungs (3.47 µg/g) after 30 minutes of application, which were higher than after intraperitoneal injections. CONCLUSION: The relatively high tissue levels remained for 120 min monitoring. Selegiline levels in the brain (1.69 µg/g) and in the testes (1.88 µg/g) were also considerably higher than following intraperitoneal administration during the entire period of observation (15 to 120 min).