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Biomedical subjects

A Nair

Publications and source records attributed to A Nair.

At least 19 recordsLinked to original sources
PubMed2006

Cyclic AMP response element binding protein and brain-derived neurotrophic factor: molecules that modulate our mood?

Depression is the major psychiatric ailment of our times, afflicting approximately 20% of the population. Despite its prevalence, the pathophysiology of this complex disorder is not well understood. In addition, although antidepressants have been in existence for the past several decades, the mechanisms that underlie their therapeutic effects remain elusive. Building evidence implicates a role for the plasticity of specific neuro-circuitry in both the pathophysiology and treatment of depression. Damage to limbic regions is thought to contribute to the etiology of depression and antidepressants have been reported to reverse such damage and promote adaptive plasticity. The molecular pathways that contribute to the damage associated with depression and antidepressant-mediated plasticity are a major focus of scientific enquiry. The transcription factor cyclic AMP response element binding protein (CREB) and the neurotrophin brain-derived neurotrophic factor (BDNF) are targets of diverse classes of antidepressants and are known to be regulated in animal models and in patients suffering from depression. Given their role in neuronal plasticity, CREB and BDNF have emerged as molecules that may play an important role in modulating mood. The purpose of this review is to discuss the role of CREB and BDNF in depression and as targets/mediators of antidepressant action.

Affect↗
PubMed2005

Multi-disciplinary rehabilitation for acquired brain injury in adults of working age.

BACKGROUND: Evidence from systematic reviews demonstrates that multi-disciplinary rehabilitation is effective in the stroke population, where older adults predominate. However, the evidence base for the effectiveness of rehabilitation following acquired brain injury (ABI) in younger adults is not yet established, perhaps because there are different methodological challenges. OBJECTIVES: To assess the effects of multi-disciplinary rehabilitation following ABI in adults, 16 to 65 years. To explore approaches that are effective in different settings and the outcomes that are affected. SEARCH STRATEGY: We used a wide range of sources including: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966-2004), EMBASE (1988-2004), CINAHL (1983-2004), PsycLIT (1967-2004), AMED, the National Research Register 2004 and ISI Science Citation Index (1981-2004). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing multi-disciplinary rehabilitation with either routinely available local services or lower levels of intervention; or trials comparing intervention in different settings or at different levels of intensity. Quasi-randomised and quasi-experimental designs were also included, providing they met pre-defined methodological criteria. DATA COLLECTION AND ANALYSIS: Trials were selected by two authors independently, and their methodological quality rated, again by two independent authors. A third reviewer arbitrated when disagreements could not be resolved by discussion. A 'best evidence' synthesis was performed by attributing levels of evidence, based on methodological quality. Trials were sub-divided in terms of severity of ABI and the setting and type of rehabilitation offered. MAIN RESULTS: Ten trials were identified of good methodological quality and four of lower quality. Within the subgroup of predominantly mild brain injury, 'strong evidence' suggested that most patients make a good recovery with provision of appropriate information, without additional specific intervention. For moderate to severe injury, there is 'strong evidence' of benefit from formal intervention. For patients with moderate to severe ABI already in rehabilitation, there is strong evidence that more intensive programmes are associated with earlier functional gains, and 'moderate evidence' that continued outpatient therapy can help to sustain gains made in early post-acute rehabilitation. There is 'limited evidence' that specialist in-patient rehabilitation and specialist multi-disciplinary community rehabilitation may provide additional functional gains, but the studies serve to highlight the particular practical and ethical restraints on randomisation of severely affected individuals for whom there are no realistic alternatives to specialist intervention. AUTHORS' CONCLUSIONS: Problems following ABI vary; different services are required to suit the needs of patients with different problems. Patients presenting acutely to hospital with moderate to severe brain injury should be routinely followed up to assess their need for rehabilitation. Intensive intervention appears to lead to earlier gains. The balance between intensity and cost-effectiveness has yet to be determined. Patients discharged from in-patient rehabilitation should have access to out-patient or community-based services appropriate to their needs. Those with milder brain injury benefit from follow-up, and appropriate information and advice. Not all questions in rehabilitation can be addressed by traditional research methodologies. There are important questions still to be answered and future research should employ the most appropriate methodology.

Adolescent↗
PubMed2005

A novel mechanism for the modulation of luteinizing hormone receptor mRNA expression in the rat ovary.

Luteinizing hormone receptor (LHR) is a G-protein-coupled receptor that exerts its effects mainly through increased cAMP synthesis. Our previous studies have shown that a ovarian cytosolic protein, designated as LHR mRNA binding protein (LRBP) is an important regulator of the steady state levels of LHR expression. To test whether LHR mRNA expression is modulated by cAMP through LRBP activity, we used rolipram, a type IV phosphodiesterase inhibitor that is known to promote intracellular cAMP accumulation. On day 4 of pseudopregnancy, rats were treated with rolipram (1.25 mg/injection) to raise intracellular levels of cAMP. In order to maintain higher cAMP levels, up to four injections of rolipram were given, with the last injection 4 h before collecting the ovaries. Measurement of cAMP levels showed an increase (p< or =0.05) at 8, 12, and 24 h after rolipram injections at total dosages of 2.5, 3.75 and 5.0 mg/rat, respectively. Northern blot analysis of LHR mRNA showed that rolipram treatment also markedly reduced ovarian LHR mRNA levels by up to 75%. LHR mRNA binding activity of LRBP, assayed by RNA electrophoretic mobility shift analysis, using S-100 fractions from control or rolipram-treated ovaries showed increased LHR mRNA binding activity in the S-100 fractions from rolipram treated groups. These data indicate that chronic elevation of ovarian cAMP leads to a decreased expression of LHR mRNA with a concomitant increase in LHR mRNA binding activity of LRBP.

Animals↗
PubMed2005

October 2004: a 49-year-old man with progressive dementia.

October 2004. A 49-year-old right-handed man developed progressive cognitive difficulties over a 4-month period. There was impairment in recent memory, calculations and language. He also developed fatigue, weight loss, gait imbalance and urinary incontinence. Past history included transfusion-associated Hepatitis C. Neurologic exam showed mild dysarthria, dysnomia, left sided neglect, bilateral Babinski signs, and a prominent grasp reflex. Laboratory testing provided no positive etiologic data. An EEG showed generalized intermittent slowing suggestive of a diffuse encephalopathy and decreased background in the right hemisphere, suggestive of a structural lesion. MRI showed multiple areas of high signal on FLAIR imaging and patchy enhancement. FDG-PET showed multi-focal areas of increased uptake, correlating with the abnormal areas on MRI, on a background of decreased uptake. A 4-vessel cerebral angiogram showed no abnormalities. A brain biopsy showed diffuse infiltrates of large malignant cells that were immunoreactive with antibodies to CD20, diagnostic of diffuse large B cell lymphoma. In summary, the clinical presentation suggested bilateral hemispheric involvement, which was supported by physical examination, EEG, MRI, and PET scans. The differential diagnosis for this presentation is limited to demyelinating disease such as multiple sclerosis, vascular dementia, and infiltrating neoplasm such as glioblastoma multiforme or lymphoma. Diagnosis was made by morphologic and immunohistochemical analysis of brain tissue.

Brain Neoplasms↗
PubMed2004

Disrupted spermine homeostasis: a novel mechanism in polyglutamine-mediated aggregation and cell death.

Our data suggest a novel mechanism whereby pathological-length polyglutamine (polyQ) proteins promote the spermine synthetic pathway, increasing polyQ-aggregation and cell death. As detected in a cell-free turbidity assay, spermine promotes aggregation of thio-polyQ62 in a dose-dependent manner. Using a stable neuronal cell line expressing pathological-length [polyQ57-yellow fluorescent protein (YFP) (Q57)] or non-pathological-length [polyQ19-YFP (Q19)] polyglutamine protein, we show that multiple steps in the production of polyamines are affected in Q57 cells, suggesting dysfunctional spermine homeostasis. As the building block for spermine synthesis, arginine transport is significantly increased in neuronal cell lines stably expressing Q57. Q57 lines displayed upregulated basal and inducible arginase I activities that were not seen in polyQ19-YFP lines. Normal induction of spermidine/spermine N-acetyltransferase in Q19 lines regulating back-conversion of spermine, thereby reducing spermine levels, however, was not observed in Q57 lines. Pharmacological activation of ornithine decarboxylase (ODC), a key enzyme of the polyamine synthetic pathway, increased cellular aggregates and increased cell death in Q57 cells not observed in Q19 cells. Inhibition of ODC by difluoromethylornithine prevented basal and induced cell death in Q57 cells, demonstrating a central role for polyamines in this process.

Acetyltransferases↗
PubMed2003

Organochlorine and organophosphorus pesticide residues in breast milk from Bhopal, Madhya Pradesh, India.

HCH isomers, endosulfan, malathion, chlorpyrifos, and methyl-parathion were monitored in human milk samples from Bhopal, Madhya Pradesh. The endosulfan concentrations were highest and exceeded the sigma-HCH, chlorpyrifos, and malathion concentrations by 3.5-, 1.5-, and 8.4-fold, respectively. Through breast milk, infants consumed 8.6 times more endosulfan and 4.1 times more malathion than the average daily intake levels recommended by the World Health Organization. A correlation analysis (r values) between mothers' age and the content of the chemicals accumulated in breast milk indicated a substantial degree of correlation for malathion (r = 0.5). The other chemicals showed low to negligible correlation with donor age.

Environmental Monitoring↗
PubMed2002

Effect of aflatoxins on testicular steroidogenesis and amelioration by vitamin E.

The potential of aflatoxin to affect testicular steroidogenesis and its amelioration by vitamin E was assessed in the present investigation. Oral administration of aflatoxin (25 and 50 microg/animal/day) for 45 days to adult mice caused, as compared with control, a dose-dependent significant rise in cholesterol content. However, the activities of 3beta- and 17beta-hydroxysteroid dehydrogenases and serum testosterone levels were significantly reduced in aflatoxin-treated mice as compared with the controls. Pretreatment with vitamin E (2 mg/animal/day, orally) significantly ameliorated aflatoxin-induced changes as compared with aflatoxin treatment alone. The present investigation clearly indicates that vitamin E ameliorates aflatoxin-induced changes in steroidogenesis.

17-Hydroxysteroid Dehydrogenases↗
PubMed2002

Hypokalemic paralysis in pregnancy.

Hypokalemic paralysis is an uncommon entity with varied etiology. Renal tubular acidosis is an unusual cause of this disorder. Its occurrence with pregnancy is rare. We report such a case and mention the implications of the association and review relevant literature breifly.

Acidosis, Renal Tubular↗
PubMed2001

Assessing spectral algorithms to predict atherosclerotic plaque composition with normalized and raw intravascular ultrasound data.

Spectral analysis of backscattered intravascular ultrasound (IVUS) data has demonstrated the ability to characterize plaque. We compared the ability of spectral parameters (e.g., slope, midband fit and y-intercept), computed via classic Fourier transform (CPSD), Welch power spectrum (WPSD) and autoregressive (MPSD) models, to classify plaque composition. Data were collected ex vivo from 32 human left anterior descending coronary arteries. Regions-of-interest (ROIs), selected from histology, comprised 64 collagen-rich, 24 fibrolipidic, 23 calcified and 37 calcified-necrotic regions. A novel quantitative method was used to correlate IVUS data with corresponding histologic sections. Periodograms of IVUS samples, identified for each ROI, were used to calculate spectral parameters. Statistical classification trees (CT) were computed with 75% of the data for plaque characterization. The remaining data were used to assess the accuracy of the CTs. The overall accuracies for normalized spectra with CPSD, WPSD and MPSD were, respectively, 84.7%, 85.6% and 81.1% (training data) and 54.1%, 64.9% and 37.8% (test data). These numbers were improved to 89.2%, 91.9% and 89.2% (training) and 62.2%, 73% and 59.5% (test) when the calcified and calcified-necrotic regions were combined for analysis. Most CTs misclassified a few fibrolipidic regions as collagen, which is histologically acceptable, and the unnormalized and normalized spectra results were similar.

Adult↗