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Cerebelo/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/genética , Proteínas do Olho/genética , Proteínas de Membrana/genética , Ataxias Espinocerebelares/diagnóstico por imagem , Ataxias Espinocerebelares/genética , Adulto , Humanos , Masculino , Mutação/genéticaRESUMO
BACKGROUND: Cognitive impairment is commonly seen in patients with Duchenne muscular dystrophy (DMD). Few studies have shown a correlation between loss of different isoforms of the DMD gene and cognitive impairment. OBJECTIVE: The objective of the study was to determine whether correlation exists in the location of mutation in DMD gene or loss of different isoforms and cognitive impairment in children with DMD in the Indian population. MATERIALS AND METHODS: Ten children were evaluated. Gene mutation analysis was done by multiplex ligation-dependent probe amplification method. The isoforms affected were inferred from mutation location in each of these patients. Binet Kamat Intelligence Test (BKT) and Bender Gestalt test (BGT) were administered. RESULTS: All male patients were aged between 4 and 9 years. Genetic analysis showed deletion in all patients, with seven having deletion in "hotspot" regions (exon 43-52). Psychometric analysis by BGT and BKT showed mean score of 8.6 and mean IQ score of 85.5, respectively. Comparison between patients with hotspot mutations and mutations in other regions, for mean IQ score and BGT score, was statistically significant (P = 0.132 and P = 0.005, respectively). The difference in the IQ score between patients with isolated Dp427 loss (n = 3) and cumulative Dp427/Dp260/Dp140utr loss (n = 6) was statistically significant (P = 0.011). Visuomotor functioning was more impaired in patients with isolated Dp427 loss. CONCLUSION: The role of cumulative loss of isoforms along with importance of loss of Dp140pc isoform was seen in our study. One patient with loss of Dp140utr isoform had intellectual impairment which is not commonly seen. Visuomotor functioning is more affected in more upstream mutations as shown in our study.
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BACKGROUND AND PURPOSE: The Magnitude of Drug-resistant Epilepsy (DRE) in India, being unknown, takes a heavy toll on the patients and society in the form of prolonged dependence, unemployment, morbidity and mortality. We tried to explore the clinical, electro-physiological, neuro-imaging and drug-response spectrum of DRE patients in Eastern India in our study. METHODS: During the period of January 2014 to December 2015, epilepsy patients were treated and DRE patients were identified according to International League Against Epilepsy criteria. We isolated those patients and studied them in a special clinic. RESULTS: Among 2,153 patients treated in Neurology out-patient department, 243 (11.3%) patients were drug-resistant. Among the DRE patients, 63% were male. Age-wise 40%, 30.5% & 18.1% patients were presented in their first, second and third decades respectively. Males were more affected in 0-5 years age group while females in 6-10 years age group. Various seizures types were found alone or in combination. Males were mostly affected by generalized tonic clonic seizure and myoclonus and females by complex partial seizure. Positive family history was higher in partial seizure group. Electroencephalographic (EEG) abnormalities were common with structural lesions in brain. EEG findings in different etiologies were varied with a large number of DRE patients who were found to have normal EEG. Females were higher medicine non-compliant. CONCLUSIONS: The spectrum was pointed towards gender predilection for specific age group and also for seizure types. Idiopathic cases were most common in DRE, pointing towards the need of newer investigations. Normal EEG could be found even in a DRE patient. Non-compliance was more in females.
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Wilson's disease is a metabolic disorder which presents with hepatitis or hepatic decompensation commonly. Neurologic manifestations are late and include movement disorders, personality changes, and seizures. Magnetic resonance imaging (MRI) brain shows high signal changes in putamen, lentiform nucleus, thalamus, and brainstem. White matter lesions are rare. We report a child of Wilson's disease who presented to us with dystonia, rigidity, myoclonus and had symmetrical white matter changes in the fronto-parietooccipital region. Diffusion restriction in bilateral frontoparietal areas was also seen which is rare in chronic cases like ours. Atypical MRI characteristics should be considered in patients with clinical signs of neurological involvement in Wilson's disease as it is a devastating but treatable disease.
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Neovascularização Patológica/complicações , Doenças do Sistema Nervoso/complicações , Vasculite Retiniana/complicações , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Neovascularização Patológica/diagnóstico , Radiografia , Retina/patologia , Vasculite Retiniana/diagnóstico , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Tomógrafos ComputadorizadosRESUMO
This study dealt with the development of cryopreservation protocol for Nandus nandus, which entailed a number of experiments. Sperm was collected by sacrificing males. The collected sperm was suspended in extenders. Activation of sperm motility was evaluated in different osmolalities of NaCl. Motility of sperm decreased as the osmolality of the extender increased and was completely inhibited at almost 319 mOs mol/kg. To evaluate the toxicity of cryoprotectant, sperm was incubated with DMSO, methanol and ethanol at 5%, 10% and 15% concentrations, respectively, for 5-35 min. Five and ten percent of cryoprotectants produced better motility during 5 and 10 min incubation. Sperm incubated with 15% cryoprotectant seemed to be toxic and this concentration was excluded in the subsequent trials. Three extenders, namely, Alsever's solution, egg-yolk citrate and urea egg-yolk and three cryoprotectants, DMSO, methanol and ethanol were employed to preserve the sperm. Alsever's solution with 10% DMSO showed best performance producing 90.0±1.8% and 75.0±2.5% equilibration and post-thaw motility followed by that of 82.5±4.2% and 62.5±5.5% with Alsever's solution plus methanol, respectively. Between two diluents, sperm preserved with Alsever's solution plus DMSO produced highest fertilization (76.7±3.3%) and hatching (43.8±7.9%) while fresh sperm yielded 83.3±6.7% and 64.0±10.4% fertilization and hatching, respectively. The protocol developed through the study can be applied for long-term conservation of genetic materials of the endangered fish N. nandus and the cryopreserved sperm can be used in artificial breeding for generating new individuals.
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Criopreservação/veterinária , Espécies em Perigo de Extinção , Perciformes/fisiologia , Preservação do Sêmen/veterinária , Espermatozoides/citologia , Animais , Criopreservação/métodos , Crioprotetores/toxicidade , Dimetil Sulfóxido/toxicidade , Etanol/toxicidade , Feminino , Fertilização , Masculino , Metanol/toxicidade , Concentração Osmolar , Preservação do Sêmen/métodos , Motilidade dos Espermatozoides , Espermatozoides/efeitos dos fármacosRESUMO
Community-based longitudinal study on stroke is rare in India. It has been predicted that the stroke incidence will be higher in developing countries than developed countries. Hence a five years prospective study was planned to carry out in the rural Bengal, India based on WHO protocol to determine the incidence rate, risk factors, morbidity and mortality profile of stroke. In a two-stage procedure, 20717 subjects out of 20842 people from a cluster of 12 villages was surveyed by house-to-house method and the screened cases were examined by a team of neurologists including post stroke surveillance for one year. Altogether 128 first ever stroke cases were detected over 5 years showing an average annual incidence rate of 123.57 per 100,000 persons [age adjusted incidence rate (AAIR)--262/100,000; based on USA population, 1990] and sex-specific AAIR (274/100,000) among women is slightly higher than men (253/100,000). Age-specific stroke incidence rate showed increasing rate from fourth decade up to seventh decade in both sexes when the rate was maximum. First 30 days mortality recorded was 18% with men suffering twice than women. Follow-up after one year revealed speech improvement in 47%, residual spasticity in 46% and independency in activities daily living in 62% of cases. Age and sex matched case control study has shown that hypertension (OR - 2.79), heart disease (OR - 6.20) and smoking (OR - 3.92) are significant risk factors. This study had indicated a higher age adjusted incidence rate of stroke in India as compared to that of developed country and hypertension, heart disease and smoking are important risk factors.
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Vigilância da População/métodos , Características de Residência , Saúde da População Rural/estatística & dados numéricos , Acidente Vascular Cerebral/mortalidade , Adulto , Idoso , Feminino , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
The study was conducted to determine the prevalence of neurological diseases in a rural community in Eastern India through a community based survey with the help of trained doctors following on WHO protocol (1981) translated in local vernacular, among 20842 rural residents (male-11037, female-9805, census India-1991, the State of West Bengal in Eastern India) over a period of one yearfrom May 1992 to April 1993 in two phases. Professionals screened the patients by house to house survey in the first phase and later on they were examined in details in temporary clinics in second phase. A total of 606 patients were identified and classified according to well-defined diagnostic criteria. The commonest diseases per 100,000 were headache: 870, vertebral diseases with neurological involvement: 540, seizure disorders: 360, vertigo: 230, stroke: 147, movement disorders: 140, peripheral neuropathy: 80. The age and sex specific prevalence showed increasing frequency of neurological disorders with advancing age in both genders excepting slight dip in the fourth and fifth decades among females. In the present study prevalence of headache, epilepsy, stroke and Parkinson's disease was lower than that of in the Western countries. Different inclusion criteria, multiethnicity, different environmental factors, poor medical facility and insufficient number of aged population may be responsible for lower prevalence of chronic neurological disorders as compared to Western countries. Increase in the life expectancy in future will lead to increasing burden of chronic neurological diseases in absolute term in Indian society considering the one billion population at present.
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Doenças do Sistema Nervoso/epidemiologia , População Rural , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
Seventeen novel analogues of human calcitonin gene-related peptide(8-37) (hCGRP(8-37)) were synthesized by solid-phase methods and purified to apparent homogeneity by semipreparative cation exchange and/or reversed-phase high-performance liquid chromatography. The C-terminal Phe was replaced by Gly, cyclohexylalanine (Cha), Tyr, all four isomers of beta-methylphenylalanine (beta-MePhe), and l- and d-tetrahydroisoquinoline carboxylic acid (Tic), resulting in analogues 3-11. For the synthesis of the beta-MePhe-containing analogues 6-9, crystallization was used to separate a mixture of all four isomers of beta-MePhe into the erythro pair of enantiomers (2S,3S, 2R,3R) and the threo pair of enantiomers (2S,3R, 2R,3S), which were then converted to Fmoc derivatives and used in two separate syntheses. Two diastereomeric peptides were obtained from each synthesis and were separated by RP-HPLC to yield enantiomerically pure 6-9. Substitution of Tyr for Phe caused no change in binding affinity at CGRP receptors. All other substitutions for Phe resulted in substantial reductions in binding affinity. Indeed, no binding was observed for analogues 7, 9, and 11, all of which contained a d-amino acid residue in the C-terminal position, and the binding affinities of the remaining analogues were >10-fold lower than that of h-alpha-CGRP(8-37). These data suggest that a conformationally flexible phenyl ring in the C-terminal position of h-alpha-CGRP(8-37) is preferred for high-affinity binding to CGRP receptors. Acetylation, benzoylation, and benzylation of the N-termini of h-alpha-CGRP(8-37) and h-beta-CGRP(8-37) produced analogues 12-14 and 16-18, respectively. A byproduct was isolated by RP-HPLC from the resin-cleaved crude product of each benzylated analogue, which was characterized as the dibenzylated derivative of h-alpha-CGRP(8-37) and h-beta-CGRP(8-37) (analogues 15 and 19, respectively). Amino acid analysis and (1)H NMR showed that the second benzyl group was located on the C4 carbon of the imidazole ring of His(10). Radioligand binding experiments showed that derivatizing the N-termini substantially increased binding affinities at CGRP receptors. The benzoylated and dibenzylated derivatives had the highest affinities, which were approximately 50-fold greater than those of h-alpha-CGRP(8-37). Functional experiments confirmed that the N-terminally derivatized analogues of h-alpha-CGRP(8-37) are antagonists that are more potent than h-alpha-CGRP(8-37). In conclusion, these studies underscore the importance of Phe(37) of h-alpha-CGRP(8-37) for binding to CGRP receptors and have identified the N-terminus and His(10) as two positions that can be used for the design of antagonists with increased affinity for CGRP receptors.
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Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Peptídeo Relacionado com Gene de Calcitonina/síntese química , Fragmentos de Peptídeos/síntese química , Animais , Peptídeo Relacionado com Gene de Calcitonina/química , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Vasos Coronários/metabolismo , Vasos Coronários/fisiologia , Humanos , Técnicas In Vitro , Membranas , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/fisiologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/farmacologia , Ensaio Radioligante , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/agonistas , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo , Relação Estrutura-Atividade , SuínosRESUMO
There are about 20 epidemiological studies on epilepsy from different parts of India. They include both rural and urban studies. The prevalence rate stands at around 5/1000 population (at this rate present estimate of total epileptics in this country is about 5 million) and incidence rate varies from 38 to 49.3 per 100,000 population per year from two community-based studies in India. Case-control studies indicate that febrile seizures, family history of epilepsy and head trauma are significant risk factors. Type of seizure pattern showed maximum number of cases belonged to generalised seizures which is different from Western countries where partial seizure is the commonest variety. Treatment gap, which is a measure of per cent of patient populations not receiving the treatment, estimated to be up to 73.7% to 78% in India. Aetiology is unknown in about two-thirds of cases. Hot water epilepsy is unique in South India and single solitary ring enhancing lesion in brain imaging is a common feature in Indian subcontinent. Evaluation of prevalence study indicates that more case-control studies to find out the aetiology, pharmaco-economic study to find out the affordable drug for general public and mass health education should be undertaken to dispel the social stigma and to bring about change in the attitude about the disease.
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Epilepsia/epidemiologia , Epilepsia/classificação , Epilepsia/etiologia , Epilepsia/terapia , Humanos , Incidência , Índia/epidemiologia , Prevalência , PrognósticoRESUMO
Eighteen novel bicyclic 1-substituted benzyl octahydro- and tetrahydroisoquinolines were synthesized and evaluated for human thromboxane A(2)/prostaglandin H(2) (TP) receptor affinity and antagonism of TP receptor-mediated platelet aggregation. In both cases, potency depended more on the presence of methoxy groups on the 1-benzyl moiety than on nitrogen substitution or extent of oxidation of the isoquinoline ring system. The most potent of the bicyclic compounds retained the 5,8-ethanooctahydroisoquinoline ring structure of the parent molecule (1) and required the 3,4,5-trimethoxybenzyl substitution pattern found in the well-characterized tetrahydroisoquinoline antiplatelet agent trimetoquinol. Differences in nitrogen substituent SAR were noted between the mono-methoxylated compounds and the 3,4,5-trimethoxybenzyl derivatives.
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Isoquinolinas/síntese química , Agregação Plaquetária/efeitos dos fármacos , Receptores de Prostaglandina/antagonistas & inibidores , Receptores de Tromboxanos/antagonistas & inibidores , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Humanos , Concentração Inibidora 50 , Isoquinolinas/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/farmacologia , Ligação Proteica , Receptores de Tromboxano A2 e Prostaglandina H2 , Relação Estrutura-AtividadeRESUMO
Bacterial peptidoglycan is composed of a network of beta-[1,4]-linked glyan strands that are cross-linked through pendant peptide chains. The final product, the murein sacculus, is a single, covalently closed macromolecule that precisely defines the size and shape of the bacterial cell. The recent increase in bacterial resistance to cell wall active agents has led to a resurgence of activity directed toward improving our understanding of the resistance mechanisms at the molecular level. The biosynthetic enzymes and their natural substrates can be invaluable tools in this endeavor. While modern experimental techniques have led to isolation and purification of the biosynthetic enzymes utilized in peptidoglycan biosynthesis, securing useful quantities of their requisite substrates from natural substrates has remained problematic. In an effort to address this issue, we report the first total synthesis of lipid II (4), the final monomeric intermediate utilized by Gram positive bacteria for peptidoglycan biosynthesis.