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1.
J Helminthol ; 97: e72, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37681419

RESUMO

In this study, morphological and molecular features were used to identify a new Steinernema sp. from Chhattisgarh, India. Morphological and molecular features provide evidence for placing the new species into the "bicornutum" clade. The new species is characterized by the following morphological features: infective juveniles with a body length of 587 (494-671) µm; a distance from the anterior end to excretory pore of 46 (43-50) µm; a distance from anterior end to nerve ring of 72 µm (61-85 µm); and E% of 88 (77-97). The first-generation males are characterised by 27 genital papillae and very short spicules, with a length of 61 µm (53-67) µm. The SW% and GS% ratio of S. shori n. sp. are 139 (107-190) and 75 (62-90), respectively. The new species is further characterized by sequences of the internal transcribed spacer and partial 28S regions of the ribosomal DNA. Phylogenetic analyses show that S. shori n. sp. is most closely related to S. abbasi, S. kandii, and S. yirgalemense.


Assuntos
Rabditídios , Animais , Masculino , Filogenia , Índia , Rabditídios/genética , DNA Ribossômico/genética , Genitália
2.
Brain ; 141(9): 2561-2575, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-30007309

RESUMO

We recently demonstrated that microRNA-218 (miR-218) is greatly enriched in motor neurons and is released extracellularly in amyotrophic lateral sclerosis model rats. To determine if the released, motor neuron-derived miR-218 may have a functional role in amyotrophic lateral sclerosis, we examined the effect of miR-218 on neighbouring astrocytes. Surprisingly, we found that extracellular, motor neuron-derived miR-218 can be taken up by astrocytes and is sufficient to downregulate an important glutamate transporter in astrocytes [excitatory amino acid transporter 2 (EAAT2)]. The effect of miR-218 on astrocytes extends beyond EAAT2 since miR-218 binding sites are enriched in mRNAs translationally downregulated in amyotrophic lateral sclerosis astrocytes. Inhibiting miR-218 with antisense oligonucleotides in amyotrophic lateral sclerosis model mice mitigates the loss of EAAT2 and other miR-218-mediated changes, providing an important in vivo demonstration of the relevance of microRNA-mediated communication between neurons and astrocytes. These data define a novel mechanism in neurodegeneration whereby microRNAs derived from dying neurons can directly modify the glial phenotype and cause astrocyte dysfunction.


Assuntos
Esclerose Lateral Amiotrófica/genética , Astrócitos/fisiologia , MicroRNAs/metabolismo , Sistema X-AG de Transporte de Aminoácidos/genética , Sistema X-AG de Transporte de Aminoácidos/fisiologia , Animais , Astrócitos/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Transportador 2 de Aminoácido Excitatório/genética , Transportador 2 de Aminoácido Excitatório/fisiologia , Ácido Glutâmico/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/fisiologia , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Neuroglia/metabolismo
3.
Neurotherapeutics ; 12(2): 424-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25753730

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease leading to cell death of predominantly motor neurons. Despite extensive research in this disease, finding a way to slow the progress of the disease has been challenging. RNA-targeted therapeutic approaches, including small interfering RNA and antisense oligonucleotides are being developed for genetic forms of ALS. ALS provides an unique opportunity for the use of RNA inhibition strategies given a well-defined animal model, extensive available information regarding the causative genes, and recent experience in phase 1 clinical trial.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/terapia , Terapia Genética/métodos , RNA/metabolismo , Esclerose Lateral Amiotrófica/genética , Animais , Humanos , RNA/genética , RNA Interferente Pequeno/uso terapêutico
4.
Indian J Cancer ; 52(4): 537-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26960469

RESUMO

INTRODUCTION: Bortezomib is a novel proteasome inhibitor in myeloma. There is a paucity of data from India regarding the efficacy and tolerance to bortezomib. MATERIALS AND METHODS: All patients with newly diagnosed multiple myeloma from January 2008 to December 2011 treated with bortezomib as the first-line therapy were studied in a retrospective analysis. The primary end point was the overall rate of response. Secondary end points were the progression free survival (PFS), reversibility of renal compromise and safety of bortezomib. RESULTS: Our study included 41 patients with newly diagnosed myeloma. The overall response to bortezomib was 88.5% (complete response [CR] 31.4%, very good partial response 34.2%, partial response [PR] 22.8%). A renal response (CR renal, PR renal or Minimal Response renal combined) was documented 96.2% patients with initial renal impairment. The median time to the first renal response was 21 days. 17 patients (41.4%) had severe toxicity (Grade 3 and 4). Bortezomib induced peripheral neuropathy (BIPN) was the most common toxicity seen (53.6%) and the most common cause for discontinuation of therapy. At a median follow-up of 9 months, median PFS was not reached. DISCUSSION: The results obtained in our study are comparable with those of established studies on bortezomib. Our patient population has similar responses and renal reversibility patterns. However, they are at an increased susceptibility to BIPN, leading to discontinuation of therapy. CONCLUSION: Bortezomib as first-line therapy has a good efficacy and safety.


Assuntos
Bortezomib/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bortezomib/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Estudos Retrospectivos , Centros de Atenção Terciária
5.
Spinal Cord ; 52 Suppl 2: S21-3, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25082378

RESUMO

STUDY DESIGN: Case report. OBJECTIVES: Primary intramedullary spinal cord lymphoma is a rare entity. Studies have shown that there is a recent increase in the number of patients regardless of the status of the immunity. High index of suspicion should be kept in all patients with intramedullary tumors. Multidisciplinary approach at the earliest is required for best outcomes. SETTING: Department of Neurosurgery, Medical Oncology, Pathology and Radiation oncology. Nizam's Institute of Medical Sciences, Hyderabad, India. METHODS: We describe the case of an 11-year-old boy who presented with paraparesis and sensory loss below T10 level. On imaging, the dorsal spine showed intramedullary lesion mimicking an astrocytoma. RESULTS: Surgical decompression of the tumor was done and histopathology showed non-Hodgkin's lymphoma, diffuse large B-cell type. There were no findings suggestive of congenital or acquired immunodeficiency. After complete staging evaluation, we instituted chemotherapy with modified DeAngelis protocol. At 2 years post treatment, he is in complete remission with near normal neurological status. CONCLUSIONS: Intramedullary spinal cord diffuse B-cell lymphoma in a pediatric age group is very rare and hence requires a high index of suspicion in patients presented with myelopathy. The outcomes are encouraging with current multidisciplinary approach.


Assuntos
Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/cirurgia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/cirurgia , Astrocitoma/diagnóstico , Criança , Descompressão Cirúrgica/métodos , Diagnóstico Diferencial , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/fisiopatologia , Masculino , Procedimentos Neurocirúrgicos , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/fisiopatologia , Resultado do Tratamento
6.
Indian J Cancer ; 51(1): 5-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24947087

RESUMO

INTRODUCTION: Imatinib is a bcr-abl tyrosine kinase inhibitor which has revolutionized the treatment for chronic myeloid leukemia (CML). Even though there is much data on CML chronic phase, there is limited data on imatinib-naοve advanced phase CML. MATERIALS AND METHODS: We retrospectively analysed 90 patients with advanced phase CML (accelerated phase [AP]: 51 and blast crisis [BC]: 39), patients who received imatinib as frontline therapy. RESULTS: The median age of presentation in CML-AP and CML-BC were 32 years (12-61) and 39 years (8-59), respectively. Imatinib at 600 mg/day was initiated within 2 weeks of diagnosis. Median time to complete hematological response in both CML-AP and CML-BC was 3 months (CML-AP: 1-9 months and CML-BC: 1-14 months). At 6 months 30 (59%) CML-AP and 15 (38%) CML-BC patients achieved major cytogenetic response (MCyR), of them 24 (47%) and 10 (25.6%) being the complete cytogenetic response, respectively. At a median follow-up of 41 months, the median overall survival in CML-AP was 61 months, but in CML-BC it was 14 months. The median progression-free survival and event-free survival were 30 months and 23 months in CML-AP and 14 and 12 months in CML-BC, respectively. On univariate analysis, performance status (PS), spleen size, and MCyR predicted survival in AP, whereas in BC, platelet count, PS, and early MCyR were predictive. Non-hematologic and hematologic adverse events were observed in 80% and 60% of patients, respectively. Dose was reduced in 10% of patients for grade IV toxicity and interrupted in 30% for grade III toxicity. CONCLUSION: Front-line imatinib is an option in advanced phases of CML especially in CML-AP in low-resource countries, where stem cell transplantation and alternate TKIs are not available.


Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Crise Blástica/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Crise Blástica/mortalidade , Crise Blástica/patologia , Criança , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
7.
Neuron ; 40(3): 563-80, 2003 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-14642280

RESUMO

To investigate the in vivo role of glial cells in synaptic function, maintenance, and development, we have developed an approach to selectively ablate perisynaptic Schwann cells (PSCs), the glial cells at the neuromuscular junction (NMJ), en masse from live frog muscles. In adults, following acute PSC ablation, synaptic structure and function were not altered. However, 1 week after PSC ablation, presynaptic function decreased by approximately half, while postsynaptic function was unchanged. Retraction of nerve terminals increased over 10-fold at PSC-ablated NMJs. Furthermore, nerve-evoked muscle twitch tension was reduced. In tadpoles, repeated in vivo observations revealed that PSC processes lead nerve terminal growth. In the absence of PSCs, growth and addition of synapses was dramatically reduced, and existing synapses underwent widespread retraction. Our findings provide in vivo evidence that glial cells maintain presynaptic structure and function at adult synapses and are vital for the growth and stability of developing synapses.


Assuntos
Estradiol/análogos & derivados , Etídio/análogos & derivados , Regeneração Nervosa , Neuroglia/fisiologia , Junção Neuromuscular/crescimento & desenvolvimento , Células de Schwann/fisiologia , Sinapses/fisiologia , Testosterona/análogos & derivados , Animais , Anticorpos Monoclonais/metabolismo , Benzimidazóis/metabolismo , Bungarotoxinas/metabolismo , Contagem de Células , Proteínas do Sistema Complemento/metabolismo , Combinação de Medicamentos , Estimulação Elétrica , Etídio/metabolismo , Potenciais Pós-Sinápticos Excitadores , Cobaias , Técnicas In Vitro , Microscopia Eletrônica/métodos , Modelos Biológicos , Terminações Nervosas/metabolismo , Condução Nervosa/fisiologia , Inibição Neural , Junção Neuromuscular/ultraestrutura , Noretindrona , Aglutinina de Amendoim/metabolismo , Terminações Pré-Sinápticas/fisiologia , Compostos de Piridínio/metabolismo , Compostos de Amônio Quaternário/metabolismo , Rana pipiens , Receptores Colinérgicos , Sinapses/ultraestrutura , Sinapsinas/metabolismo , Vesículas Sinápticas , Fatores de Tempo
8.
J Neurocytol ; 32(5-8): 987-1002, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15034281

RESUMO

Like other vertebrate synapses, the neuromuscular junction (NMJ) has glial cells that are closely associated with the pre- and post-synaptic components. These "perisynaptic Schwann cells" (PSCs) cover nerve terminals and are in close proximity to the synapse, yet their role at the NMJ has remained mysterious for decades. In this review we explore historical perspectives on PSCs and highlight key developments in recent years that have provided novel insight into PSC functions at the NMJ. First among these developments is the generation of specific antibody probes for PSCs. Using one such antibody and the principle of complement-mediated cell lysis, we have developed a novel technique to selectively ablate PSCs en masse from frog NMJs in vivo. Applying this approach, we have shown that PSCs are essential for the long-term maintenance of synaptic structure and function. In addition, PSCs are essential for the growth and maintenance of NMJs during development. Probes for PSCs also allow us to observe in vivo that processes extended by PSCs guide nerve terminals during synapse development, remodeling, and regeneration. PSCs may therefore dictate the pattern of innervation at the NMJ. Finally, PSCs may also induce postsynaptic acetylcholine receptor expression and aggregation. This wealth of recent findings about PSCs suggests that these synapse-associated glial cells are a more integral and essential component of the NMJ than previously appreciated. New approaches currently being applied at the NMJ may further support the emerging view that glial cells help make bigger, stronger, and more stable synapses.


Assuntos
Neuroglia/fisiologia , Junção Neuromuscular/crescimento & desenvolvimento , Animais , Humanos , Regeneração Nervosa/fisiologia , Neuroglia/citologia , Junção Neuromuscular/citologia
9.
J Lipid Res ; 35(3): 491-500, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8014584

RESUMO

In a previous study we demonstrated that isocaloric substitution of fish oil (FO) for lard in the diet of cynomolgus monkeys resulted in low density lipoproteins (LDL) that were poorer competitors for binding of a standard 125I-labeled LDL and led to less cholesteryl ester accumulation in skin fibroblasts (Linga, V., et al. 1993. J. Lipid Res. 34: 769-778). The decreased binding and cholesteryl ester accumulation by FO LDL appeared related to the LDL apolipoprotein E (apoE) content. We hypothesized that FO LDL had reduced binding to skin fibroblasts due to a decrease in receptor active apoE. To test this hypothesis and determine the relative contribution of apoE versus apolipoprotein B (apoB) in binding of LDL to skin fibroblasts, LDL from cynomolgus monkeys fed lard or FO-containing diets were isolated, characterized, radioiodinated, and tested for binding in the absence or presence of a 10-fold molar excess of monoclonal antibody to the receptor binding domain of apoE (1D7) or apoB-100 (MB47). FO LDL were smaller, contained less apoE (E/B molar ratio = 0.48 +/- 0.03 vs. 1.85 +/- 0.22; P < 0.001), and had a weaker binding affinity (Kd = 11.3 +/- 1.6 vs. 3.8 +/- 0.80 microgram/ml; P < 0.01) compared to the lard counterparts. Furthermore, the apoE/B molar ratio of LDL appeared inversely related to the Kd for binding to skin fibroblasts. Incubation of LDL with skin fibroblasts in the presence of a 10-fold molar excess of monoclonal antibody directed at the receptor binding domain of apoB-100 (MB47) eliminated 96 +/- 3% of binding of FO LDL, but eliminated only 43 +/- 18% of binding for lard LDL. Incubation with a 10-fold molar excess of monoclonal antibody to the receptor-binding domain of apoE (1D7) eliminated only 23 +/- 6% of FO LDL binding to fibroblasts relative to a no-antibody control, but for lard LDL 44 +/- 11% of binding to fibroblasts was eliminated. Both antibodies together blocked all binding of LDL from both diet groups. In a fluid phase precipitation assay > 75% of the LDL particles from both diet groups was precipitated with saturating amounts of MB47, indicating that the proportion of LDL particles expressing this epitope was the same for both diet groups. The same assay using 1D7 showed approximately 4-fold greater precipitation of LDL in the lard versus FO group.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Apolipoproteínas E/fisiologia , Gorduras Insaturadas na Dieta/farmacologia , Fibroblastos/metabolismo , Óleos de Peixe/farmacologia , Lipoproteínas LDL/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Apolipoproteína B-100 , Apolipoproteínas B/imunologia , Apolipoproteínas B/fisiologia , Apolipoproteínas E/imunologia , Ligação Competitiva , Células Cultivadas , Ésteres do Colesterol/metabolismo , Fibroblastos/efeitos dos fármacos , Óleos de Peixe/administração & dosagem , Técnicas de Imunoadsorção , Lipoproteínas VLDL/metabolismo , Macaca fascicularis , Masculino
10.
J Lipid Res ; 34(5): 769-78, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8509715

RESUMO

Dietary fish oil (FO) has been reported to increase low density lipoprotein (LDL) receptor function resulting in lower plasma LDL concentrations in the rat (Ventura et al. J. Clin. Invest. 84: 528-537, 1989). The purpose of this study was to determine whether dietary FO, as compared to lard, affected the receptor-mediated uptake of LDL by cultured skin fibroblasts. Plasma LDL was isolated by combined ultracentrifugation and column chromatography from cynomolgus monkeys fed diets enriched in FO or lard and the effect of these two dietary fats on the binding of LDL and esterified cholesterol (EC) accumulation by cultured fibroblasts was determined. There was no difference in total plasma or LDL cholesterol concentrations between diet groups. The monkeys fed FO had significantly smaller LDL which, on average, contained less protein, phospholipid (PL), and free and esterified cholesterol compared to the LDL from monkeys fed the lard diet. FO LDL were less effective than lard LDL in competing for binding, internalization, and degradation of a standard 125I-labeled LDL by fibroblasts (11.0 +/- 2.4 vs. 3.0 +/- 0.8 micrograms LDL protein/ml for 50% displacement of binding, respectively; P = 0.013). FO versus lard LDL also resulted in less accumulation of cellular EC after a 24-h incubation with fibroblasts (7.7 +/- 0.2 vs. 13.0 +/- 0.4 micrograms EC/mg protein, respectively; P = 0.0001). In general, cellular EC accumulation was proportional to LDL particle size and LDL apoE/B molar ratio; however, LDL from the lard group resulted in greater EC accumulation even when LDL particle size and apoE content were nearly equivalent between diet groups. When LDL were isolated from the same animals by sequential ultracentrifugation, the lard LDL apoE was reduced 22% compared to column isolated LDL and this resulted in a 32% decrease in cellular EC accumulation. However, for FO LDL, apoE content was reduced 34% by sequential ultracentrifugation but this only resulted in a 10% decrease in EC accumulation. These results suggested that lard LDL contained more receptor-active apoE than FO LDL. We conclude that isocaloric substitution of fish oil for lard in the diet of cynomolgus monkeys results in LDL particles that bind less avidly to LDL receptors and in less EC accumulation in fibroblasts. The decreased binding of LDL from the FO group appears related to their decreased size and CE content as well as the decreased content of receptor-active apoE relative to the lard group.


Assuntos
Ésteres do Colesterol/metabolismo , Gorduras na Dieta/farmacologia , Óleos de Peixe/farmacologia , Lipoproteínas LDL/metabolismo , Animais , Apolipoproteínas B/análise , Apolipoproteínas E/análise , Ligação Competitiva , Células Cultivadas , Ésteres do Colesterol/química , Ácidos Graxos/análise , Fibroblastos/metabolismo , Lipoproteínas LDL/química , Lipoproteínas LDL/efeitos dos fármacos , Macaca fascicularis , Masculino , Tamanho da Partícula , Fosfolipídeos/química , Receptores de LDL/metabolismo
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