Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 10 de 10
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Seizure ; 85: 119-126, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33461030

RESUMEN

BACKGROUND: Dravet syndrome (DS) is an infantile-onset developmental and epileptic encephalopathy syndrome with limited treatment options. We aimed to evaluate the efficacy and tolerability of fenfluramine in patients with Dravet syndrome using meta-analytical techniques. METHODS: We searched for relevant randomized controlled trials and non-randomized studies involving children with Dravet syndrome on fenfluramine therapy in MEDLINE, CENTRAL, EMBASE, Google Scholar and Web of Science database (31 July 2020). The primary outcome for the efficacy of fenfluramine was reduction in monthly convulsive seizure frequency. We carried out a random effect meta-analysis focusing on efficacy and safety variables. Only Randomized Controlled Trials (RCT) were included in the meta-analysis. The risk of bias was assessed for each study, and GRADE was used to assess the quality of evidence for each outcome. RESULTS: Of 61 publications initially screened, 12 were reviewed as full-text. Seven articles including 2 RCTs, 4 uncontrolled studies (3 prospective and one retrospective study), and one case report described responses to fenfluramine in 144 DS patients (54 % male, mean age of 8.8 years, median dose of 0.4 mg/kg/day). Fenfluramine was found to be more efficacious than placebo, in terms of mean convulsive and total seizure frequency reduction (mean difference: -45.3 % (95 % CI: -48.1 %, -42.4 %, p < 0.00001) and -39.7 % (-46.7 %, -32.7 %, p < 0.00001)). A greater proportion of patients in the fenfluramine arm achieved >25 %, >50 %, >75 % and 100 % seizure reductions (odds ratios: 6.5 (3.7, 11.5, p < 0.00001), 10.6 (5.3, 21.3, p < 0.00001), 22.7(6.9, 75.3, p < 0.00001) and 9.3(1.7, 51.4, p = 0.01) respectively). The incidence of serious adverse events was not greater in the fenfluramine groups (OR: 1.02 (0.5, 2.19, p = 0.96)). CONCLUSION: Fenfluramine appears to be a safe and efficacious antiseizure medication in patients with Dravet syndrome.

2.
J Trop Pediatr ; 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32910826

RESUMEN

BACKGROUND: Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19. METHODS: Six different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles related to COVID-19 and neurological complications in children. Studies/case series reporting neurological manifestations of COVID-19 in patients aged ≤18 years, as well as case reports, as neurological complications appear to be rare. The pooled estimate of various non-specific and specific neurological manifestations was performed using a random effect meta-analysis. RESULTS: Twenty-one studies/case series and five case reports (3707 patients) fulfilled the eligibility criteria and were included in this systematic review, from a total of 460 records. Headache, myalgia and fatigue were predominant non-specific neurological manifestations, presenting altogether in 16.7% cases. Total of 42 children (1%) were found to have been reported with definite neurological complications, more in those suffering from a severe illness (encephalopathy-25, seizure-12, meningeal signs-17). Rare neurological complications were intracranial hemorrhage, cranial nerve palsy, Guillain-Barré syndrome and vision problems. All children with acute symptomatic seizures survived suggesting a favorable short-term prognosis. CONCLUSION: Neurological complications are rare in children suffering from COVID-19. Still, these children are at risk of developing seizures and encephalopathy, more in those suffering from severe illness.

3.
Seizure ; 81: 29-35, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32712376

RESUMEN

INTRODUCTION: The ongoing COVID-19 pandemic and the lockdown measures employed by the government have forced neurologists across the world to look upon telemedicine as the only feasible and practical option to continue providing health care towards children with epilepsy in home isolation. Children with epilepsy are challenging for teleconsultation as direct information from the patient is missing, regarding seizures and adverse effects, especially behavioral and psychological side effects. METHODS: Clinical and epilepsy-related details of telephonic consultations for children 1 month-18 years, performed between 26th March and 17th May 2020 in a tertiary care teaching hospital in Uttarakhand (a state of India known for hilly terrains with low per capita income) were recorded. Suitable changes in the dose/commercial brand of antiepileptic drug (AED) regimen were performed, along with the addition of new AED and referral to local practitioners for immediate hospitalization, when urgent health care issues were detected. Voice call, text message, picture/video message, and all other possible measures were employed to accumulate maximum clinical information in real-time. RESULTS: A total of 153 children(95 males [62 %], 9.45 ±â€¯3.24 years, 140 lower/middle socioeconomic status) were enrolled after screening 237 children with various neurological disorders, whose caregivers contacted for teleconsultation. A total of 278 telephone consultations performed for these 153 children (1-5 telephone calls per patient). Hundred-thirteen children were identified to have a total of 152 significant clinical events (breakthrough seizure/uncontrolled epilepsy (108), AED related (13), and unrelated systemic adverse effects (24), worsening of associated co-morbidities (7). In rest of the patients, the query of the caregiver included unavailability of AED/prescribed commercial brand in the locality, query related to the dose of drugs, proxy for a scheduled routine visit (no active issues), and concern regarding COVID-19 related symptoms and effect of COVID-19 and lockdown in children with epilepsy. Ninety-three (60 %) patients required hiking up of AED dose, whereas 29 (17 %) patients required the addition of a new AED/commercial brand. Five children were advised immediate admission to a nearby hospital. Overall, 147 (96 %) caregivers were satisfied with the quality of medical advice. CONCLUSION: Teleconsultation is one of the few feasible options with good effectiveness for providing medical advice to children with epilepsy during pandemic times.


Asunto(s)
Anticonvulsivantes/uso terapéutico , Infecciones por Coronavirus , Epilepsia/tratamiento farmacológico , Pandemias , Neumonía Viral , Telemedicina/métodos , Adolescente , Betacoronavirus , Niño , Preescolar , Manejo de la Enfermedad , Estudios de Factibilidad , Femenino , Recursos en Salud , Hospitalización , Hospitales de Enseñanza , Humanos , India , Lactante , Masculino , Neurología , Derivación y Consulta , Consulta Remota , Teléfono , Centros de Atención Terciaria , Envío de Mensajes de Texto , Comunicación por Videocoferencia
4.
J Cytol ; 35(4): 260-264, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30498302

RESUMEN

Context: Efficacy of immunocytochemistry (ICC) in determining molecular biomarkers like estrogen receptor (ER), progesterone receptors (PRs), and human epidermal growth factor receptor-2 (HER2). Aims: To evaluate biomarkers using ICC in breast cancer as per American Society of Clinical Oncology/College of American Pathology (ASCO/CAP) guidelines. Settings and Design: The study was conducted over a period of 2 years from September 2012 to August 2014 and is the first such study in eastern India. Materials and Methods: Fine needle aspiration cytology (FNAC) was done for suspected cases of breast cancers and slides were prepared using ThinPrep (TP) technology of liquid-based cytology (LBC) for ICC and corresponding biopsy specimens were processed as formalin fixed paraffin embedded (FFPE) sections for comparison. Both the LBC slides and tissue sections were subjected to immunostaining for ER, PR, and HER2. ICC was evaluated by Allred Scoring and IHC by Quick Scoring. Statistical Analysis Used: Statistical analysis done by Wilconxon Signed rank test on the SPSS program, Chicago, Illinois, USA. The results of ICC and IHC were compared by evaluation of sensitivity, specificity, kappa-value (k-value), positive predictive value (PPV), and negative predictive value (NPV). Results: The comparison of ICC with immunohistochemistry (IHC), ER, and PR showed very good correspondence rate, sensitivity, specificity, NPV, PPV, and agreement with k-value; whereas for HER2 the results were only good. Conclusion: ICC using LBC can be a useful tool in assessing biomarkers in advanced cases of breast cancer where surgery is not possible or cases where ASCO/CAP guidelines for management are not followed.

5.
Int J Biol Macromol ; 104(Pt A): 1338-1344, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28684355

RESUMEN

Fanconi anemia (FA), a cancer predisposition syndrome exhibits hallmark feature of radial chromosome formation, and hypersensitivity to DNA crosslinking agents. A set of FA pathway proteins mainly FANCI, FANCD2 and BRCA2 are expressed to repair the covalent crosslink between the dsDNA. However, FA, BRCA pathways play an important role in DNA ICL repair as well as in homologous recombination repair, but the presumptive role of FA-BRCA proteins has not clearly explored particularly in context to function associated protein-protein interactions (PPIs). Here, in-vivo, in-vitro and in-silico studies have been performed for functionally relevant domains of FANCI, FANCD2 and BRCA2. To our conclusion, FANCI ARM repeat interacts with FANCD2 CUE domain and BRCA2 C-terminal region. Interestingly, FANCD2 CUE domain also interacts strongly with BRCA2 C-terminal region. Interactions between BRCA2 CTR and functionally relevant mutations Ser222Ala (cell cycle checkpoint mutant) and Leu231Arg (DNA ICL repair mutant) present in FANCD2 CUE domain have been analysed. To our finding, these mutations abrogate the binding between FANCD2 CUE domain and BRCA2 CTR. Furthermore, (1) different domain of FANCI, FANCD2 and BRCA2 are playing important role in PPIs, (2) mutations cause the impairment in the PPIs which in turn may disrupt the DNA ICL repair mechanism.


Asunto(s)
Reparación del ADN , Proteínas del Grupo de Complementación de la Anemia de Fanconi/metabolismo , Mapeo de Interacción de Proteínas , Proteínas del Grupo de Complementación de la Anemia de Fanconi/química , Proteínas del Grupo de Complementación de la Anemia de Fanconi/genética , Mutación , Dominios Proteicos , Secuencias Repetitivas de Aminoácido
6.
Biochem J ; 471(3): 335-46, 2015 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-26285656

RESUMEN

The increase in antibiotic resistance has become a major health concern in recent times. It is therefore essential to identify novel antibacterial targets as well as discover and develop new antibacterial agents. FtsZ, a highly conserved bacterial protein, is responsible for the initiation of cell division in bacteria. The functions of FtsZ inside cells are tightly regulated and any perturbation in its functions leads to inhibition of bacterial division. Recent reports indicate that small molecules targeting the functions of FtsZ may be used as leads to develop new antibacterial agents. To identify small molecules targeting FtsZ and inhibiting bacterial division, we screened a U.S. FDA (Food and Drug Administration)-approved drug library of 800 molecules using an independent computational, biochemical and microbial approach. From this screen, we identified doxorubicin, an anthracycline molecule that inhibits Escherichia coli division and forms filamentous cells. A fluorescence-binding assay shows that doxorubicin interacts strongly with FtsZ. A detailed biochemical analysis demonstrated that doxorubicin inhibits FtsZ assembly and its GTPase activity through binding to a site other than the GTP-binding site. Furthermore, using molecular docking, we identified a probable doxorubicin-binding site in FtsZ. A number of single amino acid mutations at the identified binding site in FtsZ resulted in a severalfold decrease in the affinity of FtsZ for doxorubicin, indicating the importance of this site for doxorubicin interaction. The present study suggests the presence of a novel binding site in FtsZ that interacts with the small molecules and can be targeted for the screening and development of new antibacterial agents.


Asunto(s)
Proteínas Bacterianas/metabolismo , División Celular/efectos de los fármacos , Proteínas del Citoesqueleto/metabolismo , Doxorrubicina/farmacología , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Sitios de Unión , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/genética , Doxorrubicina/química , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Humanos , Simulación del Acoplamiento Molecular , Mutación , Bibliotecas de Moléculas Pequeñas/farmacología
7.
Artículo en Inglés | MEDLINE | ID: mdl-26030687

RESUMEN

Silver nanoparticles (SNPs) are widely used in a variety of biomedical and consumer products as an antimicrobial additive. The present study was conducted to evaluate the impacts of low-dose SNPs on intestinal physiology of tilapia (Oreochromis niloticus L.) for assessing its apparent environmental risk due to extensive commercial use. SNPs were synthesized by a chemical reduction method yielding 1-27 nm oval shaped particles. Early fingerlings of tilapia were exposed with two sublethal concentrations (0.8 and 0.4 mg L(-1)) of SNPs for twenty one days period and its impact on the intestinal physiology was evaluated by histochemistry, catalase expression, glutamate dehydrogenase activity, SDS-PAGE and gut micro flora count. Histological analysis showed thinning of intestinal wall, swelling on mucosal layer and immunohistochemical assay exhibited an enhanced catalase expression in SNPs treated fishes. Gut microflora count elicited a dose-dependent depletion and a variable SDS-PAGE profile followed by significant (P < 0.05) elevations in glutamate dehydrogenase activity in SNPs-treated fishes. This study was designed to provide a better understanding of environmentally acceptable, dose-dependent SNPs delivery in fishes and to formulate guidelines in aquatic toxicology.


Asunto(s)
Cíclidos/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/fisiopatología , Nanopartículas/toxicidad , Plata/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Catalasa/metabolismo , Intestinos/microbiología , Dosificación Letal Mediana
8.
Acta Histochem ; 116(2): 297-303, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24139688

RESUMEN

Glutamate dehydrogenase (GDH) enzyme was conventionally known as a mitochondrial marker. However, subsequently it was reported to be present in the nuclei as well. So far, the nuclear distribution of GDH has been reported in a number of organisms including yeast, rat, cow, chicken. However, the sub-cellular distribution of GDH, illustrated by in situ methods still remains elusive. Here, by assaying the GDH activity and by immuno-blotting using anti-GDH antibody in the fractionated nuclear and cytoplasmic fractions of Drosophila larvae, we demonstrate the cytoplasmic distribution of GDH. This observation was further supported by in situ immunostaining of salivary gland, Malpighian tubules and eye imaginal discs of Drosophila larvae. Collectively, our results demonstrate that in Drosophila larvae, GDH is not found in the nucleus, but is localized exclusively in the cytoplasm.


Asunto(s)
Drosophila melanogaster/enzimología , Glutamato Deshidrogenasa/metabolismo , Animales , Núcleo Celular/metabolismo , Citoplasma/enzimología , Immunoblotting , Larva/enzimología , Mitocondrias/enzimología
9.
Gene ; 512(1): 47-54, 2013 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23041126

RESUMEN

The proteolysis of the N- or the C-terminal tails of histones have recently emerged as a novel form of irreversible posttranslational modifications of histones. However, there are very few reports describing purification of a histone specific protease. Here, we report a histone H2A specific protease (H2Asp) activity in the chicken liver nuclear extract. The H2Asp was purified to homogeneity and was found to be a ~10.5kDa protein. It demonstrated high specificity to histone H2A and was an aspartic acid like protease as shown by protease inhibition assay. The H2Asp, in the in vitro cleavage assay generated a single clipped H2A product which comigrated along with histone H4 in the SDS-PAGE and migrated as a single band when single H2A was used as substrates. The expression of H2Asp was independent of age and was tissue specific, which was demonstrated only in the nuclear extracts of chicken liver and not from the same of other tissues like brain, muscles and erythrocytes. It was also seen that H2Asp activity also exists in other classes of vertebrates from Pisces to Mammals. This report forms the first such report describing purification of a histone H2A specific protease.


Asunto(s)
Núcleo Celular/enzimología , Endopeptidasas/aislamiento & purificación , Endopeptidasas/metabolismo , Extractos Hepáticos/química , Hígado/enzimología , Animales , Pollos , Histonas/metabolismo , Especificidad por Sustrato
10.
Protein Pept Lett ; 18(12): 1194-203, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21728989

RESUMEN

Glutamate dehydrogenase (GDH) enzyme is recently being reported to be present in the nucleus in addition to the mitochondria in a number of organisms. Here we investigated the distribution of GDH in liver and brain tissues of chicken. Polyclonal anti-GDH antibody against bovine GDH was raised by us, which was later shown to be immunereactive to chicken GDH. The nuclear and the mitochondrial extracts from liver and brain tissues of chicken were made as described. By quantitative immunoreactivity, it was revealed that the nuclear GDH expressed in comparable efficiencies in the liver and brain. However, the activity of the brain nuclear GDH was lower than the liver counterparts. The allosteric regulation pattern for the brain nuclear GDH was also different from the other corresponding fractions and it was speculated that the brain nuclear GDH was inactive. The liver and brain nuclear GDH were purified to homogeneity and comparison of specific activities of both the GDH ruled out the existence of any inhibitor in the brain nuclear GDH. It is hypothesized that the inactivation of the brain nuclear GDH in chicken could be due to some already known posttranslational modification. The present report throws light on the differential regulation pattern of GDH enzyme.


Asunto(s)
Encéfalo/enzimología , Núcleo Celular/enzimología , Glutamato Deshidrogenasa/metabolismo , Hígado/enzimología , Animales , Western Blotting , Bovinos , Pollos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...