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991.
Mutant HSPB1 overexpression in neurons is sufficient to cause age-related motor neuronopathy in mice
Srivastava AK Renusch SR Naiman NE Gu S Sneh A Arnold WD Sahenk Z Kolb SJ 《Neurobiology of disease》2012,47(2):163-173
The small heat shock protein HSPB1 is a multifunctional, α-crystallin-based protein that has been shown to be neuroprotective in animal models of motor neuron disease and peripheral nerve injury. Missense mutations in HSPB1 result in axonal Charcot-Marie-Tooth disease with minimal sensory involvement (CMT2F) and distal hereditary motor neuropathy type 2 (dHMN-II). These disorders are characterized by a selective loss of motor axons in peripheral nerve resulting in distal muscle weakness and often severe disability. To investigate the pathogenic mechanisms of HSPB1 mutations in motor neurons in vivo, we have developed and characterized transgenic PrP-HSPB1 and PrP-HSPB1(R136W) mice. These mice express the human HSPB1 protein throughout the nervous system including in axons of peripheral nerve. Although both mouse strains lacked obvious motor deficits, the PrP-HSPB1(R136W) mice developed an age-dependent motor axonopathy. Mutant mice showed axonal pathology in spinal cord and peripheral nerve with evidence of impaired neurofilament cytoskeleton, associated with organelle accumulation. Accompanying these findings, increases in the number of Schmidt-Lanterman incisures, as evidence of impaired axon-Schwann cell interactions, were present. These observations suggest that overexpression of HSPB1(R136W) in neurons is sufficient to cause pathological and electrophysiological changes in mice that are seen in patients with hereditary motor neuropathy. 相似文献
992.
Jyoti Jain Shashank Banait Ajit Kumar Srivastava Rahul Lodhe 《Annals of Indian Academy of Neurology》2012,15(2):163-166
Honey-bee bites which require urgent hospitalization is very rare. It is mainly seen as occupational hazards in farmers, tree dwellers and honey collectors. Common clinical presentation includes minor localized reactions in form of swelling and redness sometimes anaphylactic reaction. Infrequent major complications reported from different studies include rhabdomyolysis, acute renal failure (ARF), acute pulmonary edema, intravascular coagulation, encephalopathy and very rarely cerebral haemorrhage. Stroke due to multiple intra- cerebral infarcts along with rhabdomyolysis in patient of honey-bee bite is rare neurological complication. We report a case of 70 year man with honey-bee bite and multiple intracerebral infarcts presented as stroke, and rhabdomyolysis and ARF. When a patient presented with honey-bee bite, one should suspect serious complications. Despite advances in the understanding of pathophysiology its complications remains enigmatic and in some instances may be multifactorial. Various therapeutic interventions if started early after diagnosis reduces the possible consequences as potential reversibility of the illness. 相似文献
993.
PurposeTo evaluate sleep disturbances or sleep related events and their characteristics among patients with medically refractory epilepsy, compared to those with controlled epilepsy.MethodsIn a prospective case-controlled study, patients of medically refractory and controlled epilepsy were recruited and history pertaining to epilepsy and sleep related events and Epworth sleepiness scores were recorded and all patients underwent over night polysomnography.ResultsAmong 40 patients, 20 with medically refractory (Group 1) and 20 with controlled epilepsy (Group 2) (median age 18, range 10–35 years), the self reported sleep parameters in Group 1 patients were found to be significantly different as compared to Group 2, in terms of the duration of night time sleep, day time sleep, day time nap frequency, total sleep hours per day, excessive daytime sleepiness (EDS)(45% vs. 15%) and average sleep hours over the week prior to polysomnography. On PSG, Group 1 patients showed significantly less total sleep time [340.4 min (147–673) vs. 450.3 min (330–570)] with delayed sleep latency and REM latency, poor sleep efficiency [80.45 (40.5–98.0) vs. 95.45 (88.4–99.7)] and frequent arousals and wake after sleep onset (WASO) compared to Group 2 patients. Four patients (20%) in Group 1 compared to none in Group 2 were found to have mild obstructive sleep apnea.ConclusionsOur results indicate that medically refractory epilepsy patients believe that they spend more time sleeping, in contrast to the documented shorter sleep duration on polysomnography. This difference between perceived and actual sleep seems, by their data, to arise mainly from sleep fragmentation, disturbed architecture and the interesting finding of associated sleep apnea among the medically refractory epilepsy patients. 相似文献
994.
Prachi Srivastava Smriti Badhwar Dinu S. Chandran Ashok Kumar Jaryal Viveka P. Jyotsna Kishore Kumar Deepak 《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2019,13(3):2061-2068
AimDiabetes is associated with Renin-angiotensin-aldosterone-system (RAAS) activation. Protective role of Angiotensin (1-7) has been recently identified. The study aims to identify associations between imbalance in RAAS components with vascular endothelial dysfunction and inflammation in diabetics with newly diagnosed hypertension.MethodsBrachial Flow-mediated-dilation (FMD), Carotid Intima-media-thickness (CIMT), pulse-wave-velocity (PWV), Serum E-selectin, Vascular-Cell-Adhesion-Molecule-1 (VCAM-1), high-sensitivity C-Reactive Protein (hsCRP), Interleukin-10 (IL-10), Renin, AngiotensinII, Angiotensin-Converting-Enzyme 2 (ACE2) and Angiotensin1-7 were measured in 60 diabetic patients with newly diagnosed hypertension. Patients with AngiotensinII/Angiotensin1-7 ratio <1 were classified as Favourable-Axis (FA) group (n = 22) and those with ratio >1 were classified as Unfavourable-Axis (UA) group (n = 38).ResultshsCRP was higher [9.52 (4.64–16.19) vs 3.62 (1.77–13.09) (mg/l), p = 0.04], IL-10 was lower [2.26 (1.34–12.05) vs 10.98 (4.44–17.78) (pg/ml),p = 0.006], %FMD was lower [(5.51 ± 2.97) vs (7.66 ± 3.38) (%), p = 0.01] and CIMT was higher in UA compared to FA group [0.7 (0.55–0.79) vs 0.51 (0.49–0.65) (mm), p = 0.001]. Renin correlated positively with pressure, PWV, E-selectin and VCAM-1, opposing associations were obtained for Angiotensin1-7 and ACE2.ConclusionImbalance between AngiotensinII – Angiotensin1-7 is associated with increased inflammation and vascular dysfunction in diabetics and can contribute to development of hypertension in these patients. 相似文献
995.
996.
India is a diversified country. Just as the geography, religion, and culture of India are diverse, so are Indians' food habits. Even so, regional heterogeneity in food consumption exists across states. But it may be hypothesized that regional heterogeneity in food consumption across states has been declining. This hypothesis is based on the fact that interstate migration has been growing since 1991. The present study tested whether or not regional heterogeneity in food consumption has been declining over the years 1993-1994, 1999-2000, and 2004-2005. The authors show that regional heterogeneity declined over these periods and that both rural and urban consumers shifted their preference from cereals to non-cereals. However, the article also provides some evidence that regional disparities remain in India. Implications of this shift in consumption are discussed. 相似文献
997.
The onset of puberty is the result of an increase in secretion of hypothalamic gonadotrophin‐releasing hormone (GnRH). This action is a result of not only the development of stimulatory inputs to its release, but also the gradual decrease in inhibitory inputs that restrain release of the peptide prior to pubertal onset. Dynorphin (DYN) is one of the inhibitory inputs produced in the medial basal hypothalamus (MBH); however, little is known about what substance(s) control its prepubertal synthesis and release. Because neurokinin B (NKB) increases in the hypothalamus as puberty approaches, we considered it a candidate for such a role. An initial study investigated the acute effects of an NKB agonist, senktide, on the secretion of DYN from MBH tissues incubated in vitro. In other experiments, central injections of senktide were administered to animals for 4 days then MBHs were collected for assessment of DYN synthesis or for the in vitro secretion of both DYN and GnRH. Because insulin‐like growth factor (IGF)‐1 has been shown to play an important role at puberty, additional animals received central injections of this peptide for 4 days to assess NKB and DYN synthesis or the in vitro secretion of NKB. The results obtained show that senktide administration up‐regulates the NKB receptor protein, at the same time as suppressing the DYN and its receptor. Senktide consistently suppressed DYN and elevated GnRH secretion in the same tissue incubates from both the acute and chronic studies. IGF‐1 administration caused an increase in NKB protein, at the same time as decreasing DYN protein. Furthermore, the central administration of IGF‐1 caused an increase in NKB release, an action blocked by the IGF‐1 receptor blocker, JB‐1. These results indicate that the IGF‐1/NKB pathway contributes to suppressing the DYN inhibitory tone on prepubertal GnRH secretion and thus facilitates the puberty‐related increase in the release of GnRH to accelerate the onset of puberty. 相似文献
998.
Pietro A. Canetta Jonathan P. Troost Shannon Mahoney Amy J. Kogon Noelle Carlozzi Sharon M. Bartosh Yi Cai T. Keefe Davis Hilda Fernandez Alessia Fornoni Rasheed A. Gbadegesin Emily Herreshoff John D. Mahan Patrick H. Nachman David T. Selewski Christine B. Sethna Tarak Srivastava Katherine R. Tuttle Lisa M. Guay-Woodford 《Kidney international》2019,95(5):1209-1224
999.
Abhay Srivastava Niraj M. Bhatt Tushar P. Patel Nidheesh Dadheech Anubha Singh 《Pharmaceutical biology》2016,54(10):2061-2072
Context Oxidative stress induces apoptosis within Islets of Langerhans in diabetes mellitus (DM). Enicostemma littorale blume, herb of the Gentianaceae family is used as an anti-diabetic agent across rural India.Objective This report demonstrates potent anti-apoptotic and cyto-protective activity of Enicostemma littorale MeOH extract (EL MeOH ext.) against 50?μM H2O2 in isolated rat Islets.Materials and methods In this study, the whole plant methanolic extract of EL with doses 0.25–4?mg/mL each for the preincubation duration of 0.5–4?h against 50?μM H2O2 were tested for optimum protective dose and time by Trypan blue dye exclusion assay. Islet intracellular reactive oxygen species (ROS) was quantified by DCFDA staining and cell death using PS/PI & FDA/PI staining. Further, comet assay, biochemical assessment of caspase-3 and antioxidant enzyme activities along with immunoblotting of PARP-1, caspase-3, TNF-α activation and p-P38 MapK (stress kinase) induction was performed.Results The optimized dose of EL MeOH ext. 2?mg/mL for 2?h was used throughout the study, which significantly decreased total Intracellular ROS and cell death. Further, caspase-3 activity, PARP-1 cleavage, p-P38 MapK (stress kinase) activation and TNF-α levels, which had been significantly elevated, were normalized. Antioxidant enzymes like catalase, superoxide dismutase, reduced glutathione and glutathione peroxidase, along with Comet assay, demonstrated that pretreatment with EL MeOH ext. can augment antioxidant enzyme activities and protect from DNA damage.Discussion and conclusions Significant anti-apoptotic and cyto-protective effects were mediated by EL with Islets of Langerhans subjected to oxidative stress-induced cell death. 相似文献
1000.