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OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.
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This cross sectional, study was carried out in the department of Obstetrics and Gynaecology in Mymensingh Medical College Hospital (MMCH), Mymensingh, Bangladesh from October 2015 to September 2016. The objective of the study was to evaluate dyslipidaemia between natural and surgical menopausal women. Patients who attended the menopausal clinic of Mymensingh Medical College Hospital, Mymensingh were included in the study. For this purpose 91 patient were divided into study (n=46) and comparison (n=45) groups. Serum total cholesterol (TC), serum triglyceride (TG), Serum high density lipoprotein cholesterol (HDL-cholesterol) were estimated by colorometric method and serum low density lipoprotein cholesterol (LDL-cholesterol) was calculated by using Friedwald's formula. Age range of menopausal women was 45 to 60 years. The mean age with SD was in study group 50.26±2.57 years and control group 49.02±3.13 years. It was observed that women with surgical menopause had higher mean plasma level of total cholesterol with standard deviation 192.84±52.43mg/dl while that of mean and standard deviation of natural menopause 192.26±27.56mg/dl i.e. Mean difference was statistically insignificant (p>0.05). Mean plasma levels of Triglyceride (TG) with standard deviation (215.87±67.73mg/dl) higher in surgical menopause as compared with natural menopause (147.33±65.17mg/dl) which was statistically significant (p<0.001). There was significant rise of mean with standard deviation of HDL cholesterol in natural menopause was (44.42±8.14mg/dl) as compared to surgical menopause (34.61±8.55mg/dl) and the mean difference was statistically highly significant (p<0.001). Mean with standard deviation of plasma LDL cholesterol (122.02±49.16mg/dl) rise in surgical menopause as compared to physiological menopause (118.06±20.56mg/dl) and was statistically insignificant (p>0.05). Serum total cholesterol, serum triglyceride (TG) and serum low density lipoprotein (LDL) was found significant higher level in surgical menopause. And only serum high density lipoprotein (HDL) was found significantly higher level in physiological menopause. So, surgical menopausal women were marked dyslipidaemia.
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Lipídeos , Bangladesh , HDL-Colesterol , LDL-Colesterol , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , TriglicerídeosRESUMO
Uterine sling is a operation, done with own rectus sleeve to correct the uterine descend. If necessary correction of cystocele and/or rectocele and or perineal tear done on the same sitting. After 5 years of such operation abdomen of Mrs. X was opened due to ovarian cyst in Nirapad Hospital, Shantinagar, Dhaka, Bangladesh on August 2016. Uterus was found in normal position and size. Rectus sleeves were found attached with the uterus where it was anchored. Omentum was attached over the rectus sleeves and sealed the weak points at both lateral ends of the rectus sleeves through which the sleeves were taken to the abdominal cavity. Omentum was also attached to the posterior leaf of the broad ligaments where the sleeves were sutured to minimize the dead spaces. During this 5 years period the patient felt no discomfort or pain due to the sling or experiences any further descend of the uterus.
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Prolapso Uterino/cirurgia , Bangladesh , Feminino , HumanosRESUMO
Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy that seriously affects the pregnancy outcome. It is a disease with unknown etiology and varieties of contributing factors like hormonal changes, psychological and immunological factors. A significantly high prevalence of Helicobacter pylori among pregnant women with Hyperemesis gravidarum has been revealed recently. A descriptive, cross-sectional study was carried out at antenatal ward, Department of Obstetrics and Gynaecology, Mymensingh Medical College Hospital, Mymensingh for a period of twenty-one months among purposively selected thirty-six patients with Hyperemesis gravidarum with a view to assess the involvement of H. pylori in Hyperemesis gravidarum. Data were collected through interview, physical examinations and laboratory investigations by using case record form. Statistical analysis was performed using SPSS version 20.0 for Windows. Highest number 16(44.44%) of respondents were in age group 20 to 24 years with a mean of 23.81 years and a standard deviation (SD) of 4.55 years. Majority 29(80.56%) of the women had education less than 12 years, as many as 28(77.78%) women were housewives, and at least 14(38.89%) women had unplanned pregnancies. An overwhelming majority 29(80.56%) of women had their pregnancy duration between 8 to 12 weeks with a mean duration of 10.64 weeks and a standard deviation of 2.35 weeks. Majority 20(55.56%) of women were pregnant for first time, as many as 19(52.78%) women had duration of illness for 5 to 9 weeks. Of 16 multi-gravid women, 7(43.75%) had history of similar condition in their previous pregnancies. As many as 9 (25.00%) women had family history of similar condition in their mothers and sisters. First trimester was time of manifestation of the condition.At least 11 (30.56%) stool samples were positive for H. pylori stool antigen. Family history of Hyperemesis gravidarum and presence of H. pylori stool antigen are statistically associated (p<0.05). Pregnancy at young age, low educational status of women, nulliparity, unplanned pregnancy, past history, family history and H. pylori infection are the identified risk factors of Hyperemesis gravidarum.
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Infecções por Helicobacter , Helicobacter pylori , Hiperêmese Gravídica , Complicações Infecciosas na Gravidez , Estudos Transversais , Fezes/microbiologia , Feminino , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Humanos , Hiperêmese Gravídica/microbiologia , Gravidez , Complicações Infecciosas na Gravidez/diagnósticoRESUMO
Agomelatine is a novel antidepressant with agonistic actions at melatonergic (MT1 and MT2 receptors) and antagonistic actions at 5HT-2C receptors. Venlafaxine, a serotonin norepinephrine reuptake inhibitor, is a widely prescribed drug in depression. The present study evaluated the low dose combinations of venlafaxine and agomelatine in chronic forced swim test (chronic FST) and tail suspension test (TST) in mice. Further, the effect of above drugs and their combination was evaluated on serum pro-inflammatory cytokines and hippocampal indole amine 2, 3 dioxygenase (IDO) activity by calculating the ratios of kynurenine/tryptophan (KYN/TRP) and serotonin/tryptophan (5HT/TRP). Treatment of agomelatine (4 mg/kg, i.p.) in combination with venlafaxine (4 mg/kg, i.p.) for 3 weeks showed a significant augmenting effect on both swimming and immobility time in chronic FST and immobility time in TST as compared to animals treated with either drug alone. While venlafaxine (4 mg/kg) reversed the elevated serum levels of IL-1ß and IL-6 found in chronically stressed mice, agomelatine (4 and 8 mg/kg) failed to show such a reversal. Agomelatine alone and in combination also failed to reverse the increased activity of IDO as observed by enhanced KYN/TRP and reduced 5HT/TRP seen in chronically stressed mice indicating that the augmented antidepressant effect of venlafaxine by agomelatine is not mediated by pro-inflammatory cytokine-induced activation of IDO and further, kynurenine pathway.
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Acetamidas/administração & dosagem , Antidepressivos/administração & dosagem , Depressão/tratamento farmacológico , Depressão/metabolismo , Cinurenina/metabolismo , Cloridrato de Venlafaxina/administração & dosagem , Animais , Depressão/psicologia , Sinergismo Farmacológico , Feminino , Elevação dos Membros Posteriores/métodos , Elevação dos Membros Posteriores/psicologia , Hipnóticos e Sedativos/administração & dosagem , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Natação/psicologia , Resultado do TratamentoRESUMO
BACKGROUND: Myocardial infarction is an alarming health issue, needs great attention. The present study investigated the role of histamine-H3 receptor (H3R) agonist imetit in relationship to sympathetic and renin angiotensin system in Wistar rats. MATERIALS AND METHODS: Subcutaneous injection of isoproterenol (85 mg/kg) on last 2 consecutive days in per se group and 7 days treatment of different groups at 24 h interval induced myocardial infarction in Wistar rats. H3R agonist imetit (10 mg/kg), H3R antagonist thioperamide (5 mg/kg), losartan (10 mg/kg) were administered orally to evaluate imetit's cardioprotective potential effect by measuring plasma cardiac antioxidant markers, angiotensin II, norepinephrine levels and histopathological analysis. RESULTS: Isoproterenol significantly elevated the angiotensin II and norepinephrine levels in rat plasma. This study revealed that pre-treatment with imetit similar to losartan attenuated norepinephrine and angiotensin II levels whereas thioperamide showed its antagonistic effect by diminishing imetit's effects. Furthermore, its protective effect was confirmed by restoration of cardiac antioxidant markers and histopathological improvement of myocardium integrity. CONCLUSION: This study confirm imetit's cardioprotective potential and also reveals renin angiotensin system, sympathetic system and H3R correlation in isoproterenol induced toxicity in rats. However, molecular studies must be warranted to prove the role of H3R in myocardial infarction.
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Agonistas dos Receptores Histamínicos/farmacologia , Imidazóis/farmacologia , Isoproterenol/antagonistas & inibidores , Infarto do Miocárdio/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Tioureia/análogos & derivados , Angiotensina II/sangue , Animais , Antioxidantes/metabolismo , Cardiotônicos/antagonistas & inibidores , Cardiotônicos/farmacologia , Antagonistas dos Receptores Histamínicos H3/farmacologia , Isoproterenol/farmacologia , Losartan/farmacologia , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Norepinefrina/sangue , Piperidinas/farmacologia , Ratos , Sistema Nervoso Simpático/fisiopatologia , Tioureia/farmacologiaRESUMO
The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.
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Pelvic organ prolapse is a common morbidity among Bangladeshi women. Both patient and surgeon prefer vaginal hysterectomy for the treatment of this condition and occasionally they choose Fothergill's operation. Uterine suspension is suitable for the young women to preserve the uterus. This observational study was carried out in three teaching hospitals and two other non government hospitals for the period of 12 years among 280 patients with 1st, 2nd and 3rd degree uterine prolapse. Follow up done at 6th week , 6th month, 1st year, 5th year, 10th year and 12th year for recurrence of prolapse, dragging pain and dyspareunia. Among 280 patients >60% patients were of 26-30 years age group. In last follow up at 12th year 2(0.71%) women complained feeling of some descend of uterus, 1(0.36%) complained dragging pain in abdomen and I (0.36%) complained dyspareunia. All patients expressed satisfaction which indicates psychological well being. Uterine sling is an effective procedure to save uterus in young women to improve their quality of life.
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Procedimentos Cirúrgicos em Ginecologia/métodos , Prolapso Uterino/cirurgia , Adulto , Feminino , Humanos , Paridade , Resultado do TratamentoRESUMO
Hypertensive patients have higher prevalence of insulin resistance and are at increased risk of developing type 2 diabetes mellitus (DM). There is scarcity of data on the relationship between antihypertensive therapies and glycaemic control in Indian population. Thus, the present study was designed to investigate such association among Indian population in a University teaching hospital.The study was carried out on 177 hypertensive patients (with new onset of diabetes or without diabetes) visiting the OPD of medicine department at Majeedia hospital, New Delhi. The drug history of hypertensive patients and blood glucose levels following 1-5 yrs of antihypertensive therapy were recorded.The gender distribution of hypertensive patients reveals a higher percentage of incidences in males (53.7%) as compared to females (46.3%). Hypertensive patient without DM on beta blockers and on thiazide shows higher incidence of impaired glucose tolerance (IGT) (17.5%, 18.5%) and DM (10%, 11%) as compared to patient receiving other antihypertensive therapy. While in patients of new onset diabetes the incidence was higher with ß-blockers (56.2%) than with thiazides (31.3%) followed by calcium channel blockers (CCBs) (12.5%). There was proportionate increase in incidence with the duration of therapy (3-5 years). None of the patients who were on ACE inhibitors or on angiotensin receptor blockers (ARBs) reported any incidence of IGT or DM.To conclude, ß-blockers and thiazides increases the risk of type 2 diabetes mellitus with long term antihypertensive therapy requiring regular monitoring. CCBs have lowered risks while ACE inhibitors and ARBs are relatively free of such metabolic adverse effects.
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Anti-Hipertensivos/uso terapêutico , Glicemia/efeitos dos fármacos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Povo Asiático , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diabetes Mellitus Tipo 2/sangue , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
This observational study was done to make the Gynecologists familiar with the procedure of continuous repair of rectal mucosa and repair of the anal sphincter by other than figure of 8 sutures and to assess the effectiveness of the procedure. This study was carried out in two teaching hospitals and other two private hospitals in Dhaka city and out side. Total 20 patients were included in this study. All had fourth degree perineal tear and were repaired with the new approach. Follow up was carried out at 6th week, 12th week, and 24th weeks. Among 20 patients a large number of women were mother of one child and were of 21-25 years age group. At post operative period - wound infection was nil. Perineums were well established in all cases. On follow up at 24th week - pain in perineum and dyspareunia was nil in all cases, though this was present at early weeks in few cases. Faecal incontinence was absent in all patients by 24 weeks postoperatively. In follow up visits there was no complaint of faecal incontinence. In few cases pain was present in early post operative periods but dyspareunia was absent. So, continuous repair of anal mucosa and repair of anal sphincters other than figure of eight seems better regarding technical easiness, better compliance for the surgeon and less traumatic to the rectal mucosa and ultimately better results.
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Canal Anal/cirurgia , Períneo/lesões , Reto/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Mucosa Intestinal/cirurgia , Períneo/cirurgiaRESUMO
The present study was aimed to characterize the anticonvulsant effects of piperine in combination with well established antiepileptic drug (AED) phenytoin, in the mouse maximal electroshock (MES)-induced seizure model by using the type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs). Potential adverse-effect profiles of interactions of phenytoin with piperine at the fixed-ratio of 1:1 from the MES test with respect to long-term memory and skeletal muscular strength were evaluated along with free plasma concentration of piperine and phenytoin. Parameters of oxidative stress (glutathione, malondialdehyde), brain serotonin and serum calcium levels were also determined to probe the mechanism involved in the interaction. Test of parallelism revealed that 2 drugs were associated with non-parallel dose response effects, hence only one fixed ratio combination (1:1) was evaluated which displayed additive interaction between the 2 drugs with a slight tendency towards superadditivity. Free plasma concentrations of piperine and phenytoin revealed no significant changes in their concentrations when the drugs were combined at the fixed-ratio of 1:1. In combination, neither long-term memory nor skeletal muscular strength was impaired. Analysis of biochemical parameters showed that the piperine alone or in combination with phenytoin successfully reversed the parameters of oxidative stress and increased brain serotonin levels as compared to MES group. However, no significant alteration in the serum calcium levels was observed by any treatment. In conclusion, the combination displayed additive interaction and slight tendency towards synergistic potential with protection towards side effects associated with AED therapy and is worthy of consideration for further investigations.
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Alcaloides/administração & dosagem , Anticonvulsivantes/administração & dosagem , Benzodioxóis/administração & dosagem , Fenitoína/administração & dosagem , Piperidinas/administração & dosagem , Alcamidas Poli-Insaturadas/administração & dosagem , Animais , Cálcio/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Eletrochoque , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Memória de Longo Prazo/efeitos dos fármacos , Camundongos , Força Muscular/efeitos dos fármacos , Convulsões/tratamento farmacológicoRESUMO
Prevention of myocardial injury has been considered as the most important therapeutic challenge of today. Fibrates, the agonists of the peroxisome proliferator-activated receptor (PPAR)-a receptor, have been regarded as potent therapeutic agents in this context. Hence, the present study has been designed to investigate the effect of fibrates, i.e., Clofibrate and Fenofibrate, the potent agonists PPAR-a, on ischemia-reperfusion (I/R)-induced myocardial injury. The isolated Langendorff-perfused rat hearts were subjected to global ischemia for 30 minutes followed by reperfusion for 120 minutes. Myocardial infarct size and the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent have been conducted to assess the degree of cardiac injury. Moreover, the oxidative stress in the heart was assessed by measuring lipid peroxidation, superoxide anion generation, and reduced glutathione. Clofibrate and Fenofibrate showed cardioprotection against I/R-induced myocardial injury in rat hearts as assessed in terms of reductions in myocardial infarct size, LDH, and CK levels in coronary effluent along with reduction in I/R-induced oxidative stress. It may be concluded that the observed cardioprotective potential of Clofibrate and Fenofibrate against I/R-induced myocardial injury was due to the reductions in infarct size and oxidative stress.
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The central histaminergic actions are mediated by H(1) , H(2) , H(3) and H(4) receptors. The histamine H(3) receptor regulates the release of histamine and a number of other neurotransmitters and thereby plays a role in cognitive and homeostatic processes. Elevated histamine levels suppress seizure activities and appear to confer neuroprotection. The H(3) receptors have a number of enigmatic features like constitutive activity, interspecies variation, distinct ligand binding affinities and differential distribution of prototypic splice variants in the CNS. Furthermore, this Gi/Go-protein-coupled receptor modulates several intracellular signalling pathways whose involvement in epilepsy and neurotoxicity are yet to be ascertained and hence represent an attractive target in the search for new anti-epileptogenic drugs. So far, H(3) receptor antagonists/inverse agonists have garnered a great deal of interest in view of their promising therapeutic properties in various CNS disorders including epilepsy and related neurotoxicity. However, a number of experiments have yielded opposing effects. This article reviews recent works that have provided evidence for diverse mechanisms of antiepileptic and neuroprotective effects that were observed in various experimental models both in vitro and in vivo. The likely reasons for the apparent disparities arising from the literature are also discussed with the aim of establishing a more reliable basis for the future use of H(3) receptor antagonists, thus improving their utility in epilepsy and associated neurotoxicity.
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Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Antagonistas dos Receptores Histamínicos H3/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Epilepsia/metabolismo , Humanos , Doenças Neurodegenerativas/metabolismo , Receptores Histamínicos H3/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Depression occurs frequently with diabetes affecting the quality of life. All major classes of antidepressants have been shown to have a direct pharmacologic effect on metabolic function, which further worsens glycemic control. There were no reports on the effects of venlafaxine on glucose levels and oxidative stress in diabetic animals. The present study evaluated the effects of venlafaxine (8 and 16 mg/kg per d) on glucose homeostasis along with oxidative stress in brain in diabetic mice (streptozotocin (STZ), 40 mg/kg per d for 5 days). We observed that 21 days of administration of venlafaxine (8 and 16 mg/kg per d) in diabetic mice significantly enhanced swimming in normal and STZ-treated mice with a corresponding reduction in immobility. No significant difference in blood glucose levels was observed in diabetic and normal mice following venlafaxine treatment. Venlafaxine (16 mg/kg) reversed STZ-induced elevated thiobarbituric acid reactive substance (TBARS) levels and also restored the glutathione (GSH) levels in diabetic mice. Venlafaxine (8 and 16 mg/kg) per se does not produce any significant effect in normal animals. The results indicate a dose-dependent antidepressant action of venlafaxine in diabetes-induced depressive mice. Furthermore, the blood glucose levels were not significantly altered in normal and diabetic mice. In addition, venlafaxine exhibited a decrease in TBARS and elevation in GSH levels in mice brain. Venlafaxine drug treatment appears to be safer for depression associated with diabetes.
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Antidepressivos de Segunda Geração/farmacologia , Glicemia/metabolismo , Encéfalo/efeitos dos fármacos , Cicloexanóis/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Homeostase/efeitos dos fármacos , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Estreptozocina , Natação , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Cloridrato de VenlafaxinaRESUMO
Schizophrenia (SCZ) is a debilitating disorder afflicting around 1% of the world population. Recent literature reveals oxidative injuries contribute enormously to the pathophysiology of SCZ alongside other psychopathological disturbances. Histamine H3R-antagonists have shown dual mechanism of action in experimental models of SCZ. Firstly it prevents oxidative stress and secondly alleviates schizophrenic symptoms, particularly the negative symptoms and cognitive deficits. In the present study, histamine H3R-antagonists used were ciproxifan (3.0 mg/kg, ip) and clobenpropit (15 mg/kg, ip) markedly controlled the elevated levels of various oxidative stress markers, for example, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), superoxide dismutase, catalase, etc., as a result of augmented oxidative stress in the experimental models of SCZ such as amphetamine (0.5 mg/kg, sc) and dizocilpine (MK-801) (0.2 mg/kg, ip) induced locomotor hyperactivity, apomorphine (1.5 mg/kg, sc) induced climbing behavior and haloperidol (2.0 mg/kg, po) induced catalepsy. The results of the present study revealed that H3R-antagonists possess antioxidant activity and could serve with dual mechanism by supplementing antioxidant needs of SCZ and at the same time controlling symptoms of SCZ.
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Antioxidantes , Antagonistas dos Receptores Histamínicos H3/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Esquizofrenia/metabolismo , Anfetamina/antagonistas & inibidores , Animais , Antipsicóticos/farmacologia , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Catalase/metabolismo , Catalepsia/induzido quimicamente , Estimulantes do Sistema Nervoso Central/antagonistas & inibidores , Maleato de Dizocilpina/antagonistas & inibidores , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Glutationa/metabolismo , Haloperidol/farmacologia , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
In the present study, the effect of medroxyprogesterone (MPA) is evaluated for its effect on pentylenetetrazole (PTZ) kindling model of epileptogenesis in mice followed by evaluation on kindling-induced changes in cognitive and motor functions. To explore whether the effects are mediated via progesterone receptors, a selective antagonist of progesterone (mifepristone, MIF) was also taken. Kindling was induced by once every 2 days treatment with PTZ (25 mg/kg, i.p.) for 5 weeks. The seizure severity during induction of kindling and % incidence of animals kindled at the end of 5 weeks were recorded. The motor function was assessed using a grip strength meter, whereas spatial memory was assessed in a cross maze. MPA (5 and 10 mg/kg, i.p.) significantly reduced the seizure severity scores and produced a significant decrease in the incidence of animals kindled at the end of 5 weeks (P<0.01). A higher efficacy was observed against male mice as compared with females following MPA. MIF neither reduced nor delayed the development of PTZ-induced kindling in mice. Also, it couldn't reverse the antiepileptogenic effects of MPA. On grip strength test (GST) and spontaneous alternation behavior (SAB), a significant decline in GST and % alternation was observed in kindled mice which was reversed by pre-treatment with MPA. MIF, however, could reverse only the reduced % alternation and not grip strength (GS) in PTZ-kindled animals. The study shows that MPA has antiepileptogenic effects against development of PTZ-induced kindling in mice that may not be mediated via progesterone receptors.
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Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Excitação Neurológica/efeitos dos fármacos , Medroxiprogesterona/farmacologia , Receptores de Progesterona/agonistas , Animais , Anticoncepcionais Orais Sintéticos/farmacologia , Convulsivantes/antagonistas & inibidores , Convulsivantes/toxicidade , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Epilepsia/fisiopatologia , Feminino , Excitação Neurológica/fisiologia , Masculino , Camundongos , Pentilenotetrazol/antagonistas & inibidores , Pentilenotetrazol/toxicidade , Receptores de Progesterona/fisiologiaRESUMO
BACKGROUND AND OBJECTIVES: The present study evaluated the direct costs of active epilepsy and looked at the pattern of drug prescription and utilization in epileptic patients visiting the neuroscience centre of a national hospital of India. MATERIALS AND METHODS: A total of 134 epileptic patients were studied over a period of 4 months. Patients demography, commonly prescribed antiepileptic drugs (AEDs), socioeconomic status, direct costs, response ratio (RR) for newer drugs, and quality of life (QOLIE-10) was evaluated. RESULTS AND DISCUSSION: We found a higher percentage of male patients (67.9%) as compared with females. Most of the patients were in the age group 11-30 years and majority of them (39.6%) belonged to lower middle group. A higher percentage (68.7) of drugs was prescribed as polytherapy. Higher monthly cost was observed for some of the newer AEDs including the lamotrigine, levetiracetam, and lacosamide as compared with older drugs. Among the newer drugs, clobazam had the lowest cost. RR was calculated for 12 patients out of which 8 had a RR < -0.50. The QOL domains, following conventional or newer drugs, were not much affected. CONCLUSION: The study indicates an increasing trend toward clinical usage of newer AEDs, increasing trend of poly-therapy with significant escalations in the cost of therapy.
RESUMO
Clobenpropit, an H( 3) receptor antagonist, has been reported to modulate both the release of neurotransmitters and also the activity of histidine decarboxylase (HDC). Therefore, a decarboxylase-positive modulator, namely pyridoxine, was taken for interaction studies with clobenpropit in the electroshock (ES) model of seizures in mice and subsequent changes in brain histamine levels were estimated. A significant inhibition of ES-induced seizures was seen after the simultaneous use of clobenpropit and pyridoxine. No significant effects were evident on the brain histamine levels following this combination. The combination of clobenpropit with pyridoxine appears to exhibit beneficial pharmacodynamic interaction for the prevention of ES-induced seizures, which might not be mediated by the histaminergic mechanisms.
Assuntos
Anticonvulsivantes/uso terapêutico , Eletrochoque/efeitos adversos , Antagonistas dos Receptores Histamínicos H3/uso terapêutico , Histidina Descarboxilase/metabolismo , Imidazóis/uso terapêutico , Piridoxina/uso terapêutico , Convulsões/prevenção & controle , Tioureia/análogos & derivados , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Interações Medicamentosas , Feminino , Histamina/metabolismo , Masculino , Camundongos , Tioureia/uso terapêuticoRESUMO
Voltage-gated sodium channel blockers like phenytoin and carbamazepine have long been used in the treatment of epilepsy. Brain sodium channels continue to be an important target of many newer second-generation (fosphenytoin, oxcarbazepine, lamotrigine, felbamate, topiramate, zonisamide) and third-generation (eslicarbazepine, brivaracetam, carisbamate, fluorofelbamate, elpetrigine, lacosamide, rufinamide, safinamide, vinpocetine) antiepileptic drugs (AEDs). Some of the newer drugs show either state-dependent antiepileptic action or sodium channel subtype selectivity, although most agents do not differentiate between these channel subtypes. The present review highlights the preclinical and clinical efficacy, pharmacokinetics, drug interactions and adverse event profiles. It also addresses AED selection of sodium channel blockers that constitutes the third generation of AEDs.
Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Bloqueadores dos Canais de Sódio/farmacologia , Animais , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Ensaios Clínicos como Assunto , Sistemas de Liberação de Medicamentos , Interações Medicamentosas , Epilepsia/fisiopatologia , Humanos , Bloqueadores dos Canais de Sódio/efeitos adversos , Bloqueadores dos Canais de Sódio/uso terapêuticoRESUMO
OBJECTIVE: We explored the antibacterial prescribing patterns of physicians in ear, nose and throat (ENT) outpatient and inpatient departments (OPD, IPD) of a University Hospital, New Delhi, India. MATERIALS AND METHODS: A prospective study was conducted, with a sample size of 276 patients, who visited the ENT OPD and IPD over a period of 4 months. RESULTS: It was found that 62.68% were males, 26% patients were in the age group 26-35 years, followed by 22.8% belonging to the age group 26-35 years. Maximum number of patients were diagnosed with ear (37.3%) and throat (36.2%) infections. The most frequently prescribed antibacterials were ß-lactams (45.52%) followed by quinolones (26.31%). The most commonly used agent in penicillins was amoxicillin and clavulanic acid (21.74%), in cepahalosporins was cefpodoxime proxetil (5.49%) and in quinolones was gemifloxacin (14.41%). Further, 66.67% of the patients received single antibacterial drug and the average number of antibacterial agents prescribed per patient per course was found to be 1.58. It was also observed that 70.71% of the antibacterials were prescribed by oral route. The most concomitant conditions were found to be diabetes (10.5%), hypertension (6.16%) and coronary heart disease (5.07%). All the drugs were prescribed by their brand names and 48.91% patients showed good adherence with the prescribed therapy. CONCLUSIONS: The present work is the maiden drug utilization study conducted in ENT department at our university hospital. It highlighted some rational prescription patterns including less utilization of antibiotics in ENT infections, good adherence by patients and prescription by brand names. The data presented here will be useful in future, long-term and more extensive drug utilization studies in the hospital and in promotion of rational prescribing and drug use in hospitals.