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Biomedical subjects

A Mahadevan

Publications and source records attributed to A Mahadevan.

At least 19 recordsLinked to original sources

Neuroleptospirosis - revisited: experience from a tertiary care neurological centre from south India.

BACKGROUND & OBJECTIVES: Leptospirosis is a zoonotic disease commonly reported from south India. Neurological manifestations seen in about 10-15 per cent of cases, are protean and remain unrecognized and diverse. We evaluated the pattern of nervous system involvement in leptospirosis, among patients presenting to the emergency services of a tertiary care neurological centre in south India, and also analysed the outcome and prognostic indicators. METHODS: The diagnosis of neuroleptospirosis was based on clinical and laboratory evidence of hepatorenal syndrome, and serum or CSF positivity for antileptospira antibody by a macroscopic agglutination test (MAT) and by ELISA in a limited number of samples. RESULTS: A total of 31 patients (M:F 27:4, age range 6-68 yr, mean 36.4 +/- 14.3 yr) were treated during the five year period. Acute fever with chills and rigors, headache and vomiting were the presenting manifestations; 25 patients (81%) had altered sensorium for a period ranging from 1- 8 days, four (12.9%) being deeply comatose. Eleven (35.5%) had acute symptomatic seizures at the time of presentation. Conjunctival congestion with or without haemorrhage was seen in 12 patients (38.7%), icterus in 14 (45%) and mild hepatosplenomegaly in 11 (35.5%). Early papilloedema was observed in three. Only three patients had localizing deficits. CT scan was normal in 18 of 27 (67%), while 7 (26%) had diffuse cerebral oedema. CSF pleocytosis with lymphocytic predominance (mean 50 cells/microl) and elevated protein levels (mean 115.5 +/- 67.5 mg %) were noted. Leptospira antibody was detected in serum of all, and 5 of 22 in CSF samples. Eight patients (26%) succumbed. Deep altered sensorium at presentation and raised CSF protein were two poor prognostic indicators. Pathological study of brain in five cases revealed encephalitic features and in addition immune mediated acute disseminated encephalomyelitis (ADEM) like pathology in two cases. INTERPRETATION & CONCLUSION: Neuroleptospirosis should be considered in the differential diagnosis of neuroinfections associated with hepatorenal dysfunction, in endemic areas. Leptospira antibody can be detected in CSF also in some cases. Deep altered sensorium at presentation indicates poor prognosis.

Adolescent↗

Kindling & mossy fibre sprouting in the rat hippocampus following hot water induced hyperthermic seizures.

BACKGROUND & OBJECTIVES: Hot water epilepsy (HWE) is well recognized reflex epilepsy with possible genetic susceptibility. Rat model and human experimentation had proven that HWE is a type of hyperthermic seizure with possible kindling on repeated stimulation in animals. The present study was undertaken to investigate kindling associated with hyperthermic seizures induced by repeated hot water stimulation in the rat model and to prove hyperthermic kindling. METHODS: Epileptic seizures were induced in 36 male Wistar albino rats by means of hot water sprays at 48 h time intervals. Progression of seizure activity was investigated by studying the behaviour, severity and duration of the seizure. Threshold of rectal temperatures and timed latency for seizure induction were studied. Seizure discharges (EEG) were recorded from ventral hippocampus in six of these rats. Timm's staining was used to study the neuronal sprouting as a consequence of kindling. Studying the seizure threshold, latency, duration of seizure discharge and behavioural seizure following a stimulus-free interval of 30 days tested permanence of kindling. RESULTS: Following 8-12 episodes of hot water stimulations there was progressive epileptic activity manifested in the form of lowering of rectal temperature thresholds from 41.5 to 40.0 degrees C, drop in latency for developing seizures from 185 to 118 sec, increase in duration of hippocampal seizure discharge from 15 to 140 sec, along with progressive increase in complexity of EEG after discharges, increase in behavioural seizure severity from Grade 1 to 5 in all the rats, and neuronal sprouting observed in supragranular molecular layer and in stratum lacunosum. INTERPRETATION & CONCLUSION: Our study covered all aspects of kindling and provided a useful animal model for human hot water epilepsy. Hyperthermic seizures induced by hot water in the rat model kindle as demonstrated by Timm's staining.

Animals↗

Cerebral zygomycosis.

Fifty-six patients with cerebral zygomycosis (mucormycosis) were seen during the period 1971-2001 in two tertiary care hospitals located in south India with tropical climate and catering to neurological diseases. Forty-four patients had rhinocerebral and twelve patients had isolated central nervous system (CNS) zygomycosis. Of these, ten were culture proven (Rhizopus oryzae in eight and Mucor in two); 30 were diagnosed as probable and 16 were diagnosed possible; mixed infections were seen in three patients. Diabetes mellitus was the predisposing condition in a majority (31/44) of patients with the rhinocerebral form of zygomycosis. The tissue obtained at biopsy/autopsy in either form showed necrotic/infarcted tissue with neutrophilic infiltration with broad non-septate hyphae showing irregular branching. The outcome was poor despite surgical excision and antifungal therapy. The high concentration of spores in a mouldy environment, the bird population and improper disposal of hospital waste may facilitate healthy hosts presenting with primary CNS disease.

Adolescent↗

Peripheral neuropathy in metachromatic leucodystrophy. A study of 40 cases from south India.

BACKGROUND: There is a paucity of literature from India on metachromatic leucodystrophy (MLD), a rare metabolic disorder of childhood resulting from aryl sulfatase A (ASA) deficiency.Patients/ METHODS: Case records of histopathologically verified cases of MLD, evaluated over a period of 12 years at the National Institute of Mental Health and Neurosciences, Bangalore, India, were reviewed. RESULTS: The late infantile group (36) manifested with regression of milestones (all), delayed mile stones (14), gait abnormalities (14), and seizures (11). Despite spasticity (29), there was hypo/areflexia in 25 patients. Optic atrophy (six) was rare. Consanguinity was noted in 25 children and four had a history of similar illness in siblings. Behavioural problems dominated in the juvenile group (four), but associated cognitive decline and hyporeflexia provided a clue to the diagnosis. Low serum ASA (seven of 20), raised cerebrospinal fluid protein (five of 12), and urinary metachromatic granules (two of 32) were infrequent. Electrophysiological evidence of severe demyelinating and length dependent sensory motor neuropathy was observed in all, even in the presence of hyper-reflexia. In addition to metachromatic dysmyelinating neuropathy in all patients, sural nerve biopsy in 20 patients revealed orthochromatic deposits within perivascular macrophages, particularly among those patients with normal ASA values (11 of 14), suggesting the accumulation of other glycosphingolipids. CONCLUSIONS: This study produced some noteworthy observations: the high degree of consanguinity associated with MLD in India, the existence of MLD with normal serum concentrations of ASA, the deposition of orthochromatic lipids, and electrophysiological evidence of a partial conduction block.

Child↗

Tangier disease--a diagnostic challenge in countries endemic for leprosy.

A case of Tangier disease (TD) is reported from India. The patient had presented with indolent mononeuritis multiplex and trophic ulcers of 16 years duration mimicking Hansen's disease. He received antileprosy treatment for one and a half years. Nerve conduction studies revealed features of demyelinating neuropathy. Biopsies of the sural nerve and skin showed striking vacuolation of Schwann cells and myelin sheaths, and foamy vacuolated fibroblasts, respectively, and no evidence of Hansen's disease. Low levels of apolipoprotein A1 (ApoA1) and cholesterol in the serum and undetectable levels of high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in the blood confirmed the diagnosis of TD. This is the first reported case of TD from a tropical country-India. An attempt to establish a correct diagnosis should be made by demonstrating the histopathological and lipoprotein abnormality to avoid long term medications that are chosen empirically and are unnecessary. The importance of recognising this disease in a country where Hansen's disease is highly endemic cannot be overemphasised.

Adult↗

Carcinomatous meningitis mimicking Creutzfeldt-Jakob disease.

We report a case of carcinomatous meningitis diagnosed at autopsy that was clinically diagnosed as a case of Creutzfeldt-Jakob disease (CJD) because of rapidly evolving dementia. Pathological study revealed diffusely spreading carcinomatous meningitis, infiltrating into cortex along Virchow Robin space. Immunostaining for Prion protein was negative. Despite advances in clinical diagnosis, tissue diagnosis remains a pre-requisite for confirmation of CJD.

Creutzfeldt-Jakob Syndrome↗

Degradation of (+)-catechin by Acinetobacter calcoaceticus MTC 127.

Acinetobacter calcoaceticus MTC 127 was able to grow on catechin and protocatechuic acid (PCA) as sole carbon source. Cells induced with catechin oxidized catechin and PCA at rates higher than cells of uninduced cultures. Two aromatic compounds, PCA and phloroglucinol carboxylic acid (PGCA) were isolated from culture filtrate of cells grown in catechin and characterized by infrared spectrometry and high performance thin-layer chromatography. Moreover, A. calcoaceticus MTC 127 produced high levels of PCA compared to PGCA in the degradation of catechin. Based upon these results, a pathway for the degradation of (+)-catechin in A. calcoaceticus MTC 127 is proposed. Enzymes extracted from catechin-induced culture showed catechin oxygenase (cox) and protocatechuate 3,4-dioxygenase (pcd) activities. Catechin oxygenase was purified by column chromatography and SDS-PAGE analysis showed a single band with an apparent molecular weight of 47 kDa.

Acinetobacter calcoaceticus↗

Cloning of Acinetobacter calcoaceticus chromosomal region involved in catechin degradation.

Acinetobacter calcoaceticus utilizes catechin as sole carbon source. The chromosomal region involved in catechin catabolism was cloned in Escherichia coli DH5alpha from the genomic DNA of A. calcoaceticus. A recombinant E. coli containing 9.2 kb DNA fragment of A. calcoaceticus inserted in pUC19 showed a halo zone around the colony in plate assays, indicating the catechin utilizing ability of the clone. Enzyme assays revealed the expression of the cloned DNA fragment of A. calcoaceticus. High performance thin layer chromatography confirmed protocatechuic acid and phloroglucinol carboxylic acid as cleavage products of catechin in A. calcoaceticus and the catechin degrading ability of the clones. A. calcoaceticus followed the beta-ketoadipate pathway for catechin degradation. The sub-clone (pASCI) of this insert was sequenced and analyzed. The sequence showed three major ORFs but only ORF 2 showed similarities to other aromatic oxygenases and the sequence of ORF 2 was submitted to GenBank (AF369935).

Acinetobacter calcoaceticus↗

Low prevalence of progressive multifocal leukoencephalopathy in India and Africa: is there a biological explanation?

Infection with human immunodeficiency virus (HIV) clade C virus is the most common form of HIV infection in the world. It largely infects populations in Africa and Asia and not much is known about the neurological complications associated with the virus. Cases of progressive multifocal leukoencephalopathy (PML) have been rarely reported in the literature in the acquired immunodeficiency syndrome (AIDS) or non-AIDS populations from these regions. In this article, the authors present three recently diagnosed patients with AIDS and PML from one neurological center in India, review the diagnostic challenges faced, and speculate on the possible biological reasons, including viral strain differences as well as HIV and JC virus interactions, that may account for the low incidence.

Acquired Immunodeficiency Syndrome↗

Effect of phenol on ultra structure and plasmid DNA of Xanthomonas oryzae pv. oryzae.

Most phenolic substances of plant origin are toxic to microorganisms and they confer some degree of protection to plants against phytopathogens. Xanthomonas oryzae pv. oryzae, bacterial blight pathogen of rice (Oryza sativa) was treated with phenol (monohydroxy benzene) and its effects on the morphology and cytological changes of the bacterium were studied. Total lysis of cells occurred with 5 mM conc of phenol while at 2 mM conc, the cell walls became rough and cell contents started shrinking. Plasmids isolated from both treated (2 mM) and control cells did not show any marked difference under electron microscope except that they differed in their quantity and might influence pathogenicity.

Chromosomes, Bacterial↗

Influence of Adyar river in the coastal waters of Chennai (Madras), Bay of Bengal.

The impact of the river Adyar which is influenced by industrial wastes and domestic sewage from the city of Chennai (Madras), on the hydrobiology of coastal water in the Bay of Bengal was evaluated. Reduction in pH, dissolved oxygen (DO), nitrite, nitrate, primary productivity and increase of ammonia, phosphate, silicate, heavy metals, biological oxygen demand (BOD), chlorophyll pigments, particulate organic carbon (POC), respiration, suspended solids, ATP, and bacteria in the mixing site during low tide indicated that the Adyar water was heavily polluted and ultimately affect the quality of coastal water near the vicinity of mixing zone. The effects are diluted or nullified as the distance increased from the mixing site due to heavy mixing and littoral current. During high tide, the flow was completely stopped and little or no effect was recorded. The light, water current and wave action are the important factors which minimize the pollution impacts in the receiving coastal water.

Ammonia↗

Recent advances in the synthesis of endocannabinoid related ligands.

The chemical strategies used for the synthesis of various ligands related to the endocannabinoid system namely anandamide (AEA), 2-arachidonylglycerol (2-Ara-Gl), CB1/(vanilloid receptors) VR1, anandamide membrane transporter (AMT) and fatty acid amide hydrolase (FAAH) are described in this review. In general, the chemical synthesis of analogs with changes in the head group of AEA was quite straightforward involving the conversion of an acid to an amide or an ester. Analogs which had modifications in the end pentyl chain were more difficult to synthesize and required multistep synthetic sequences to prepare the target compounds. A facile total synthesis of 2-Ara-Gl was reported and an HPLC procedure for its identification and quantification was developed, but because of the instability of 2-Ara-Gl another synthesis was developed so that it can be stored as the more stable phenylboronate ester. Similarly the chemical synthesis of various ligands in the remaining areas of CB1/VR1, AMT and FAAH are described. A summary of the present state of knowledge about the SAR in each area is presented to help in the design and synthesis of novel ligands for the future.

Amidohydrolases↗

Brain biopsy in Creutzfeldt-Jakob disease: evolution of pathological changes by prion protein immunohistochemistry.

The formation of protease-resistant prion protein (PrPsc) is considered to be an early event in the pathogenesis of Creutzfeldt-Jakob disease (CJD) and hence its demonstration in brain biopsies by immunohistochemistry is considered diagnostic. We analysed eight brain biopsies from the frontal cortex collected from different parts of India from cases diagnosed as CJD on clinical and pathological grounds for the expression of prion protein (PrP). The duration of illness in these cases varied from 2 months to 1 year. Immunohistochemistry was carried out on paraffin sections using two different clones (KG9 and 3F4) of monoclonal antibodies to PrP. Although all eight cases showed classical features of spongiform encephalopathy of varying severity, only five of the eight cases revealed PrP(sc) in the brain tissue. The immunolabelling was focal and all areas with spongiform change were not labelled. A temporal evolution in the staining pattern was evident - particulate diffuse labelling (synaptic type) in early stages (2 months), perivacuolar deposits in intermediate stages (5-6 months), and dense plaques in late stages (12 months).

Adult↗

Highly selective CB(1) cannabinoid receptor ligands and novel CB(1)/VR(1) vanilloid receptor "hybrid" ligands.

Anandamide and the metabolically stabler analogs, (R)-1'-methyl-2'-hydroxy-ethyl-arachidonamide (Met-AEA) and N-(3-methoxy-4-hydroxy-benzyl)-arachidonamide (arvanil), are CB(1) cannabinoid and VR(1) vanilloid receptors agonists. We synthesized 1',1'-dimethylheptyl-arvanil (O-1839) and six other AEA analogs obtained by addition of either a hydroxy, cyano, or bromo group on the C-20 atom of 1,1'-dimethylpentyl-Met-AEA (O-1811, O-1812 and O-1860, respectively) or 1,1'-dimethylpentyl-arvanil (O-1856, O-1895 and O-1861, respectively). The compounds were tested for their (i) affinity for CB(1) and CB(2) receptors, (ii) capability to activate VR1 receptors, (iii) inhibitory effect on the anandamide hydrolysis and on the anandamide membrane transporter, and (iv) cannabimimetic activity in the mouse 'tetrad' of in vivo assays. O-1812 is the first ligand ever proven to be highly (500- to 1000-fold) selective for CB(1) vs both VR(1) and CB(2) receptors, while O-1861 is the first true "hybrid" agonist of CB(1)/VR(1) receptors and a compound with potential therapeutic importance. The activities of the seven compounds in vivo did not correlate with their activities at either CB(1) or VR(1) receptors, thus suggesting the existence of other brain sites of action mediating some of their neurobehavioral actions in mice.

Animals↗

Detection and analysis of chromosomal arsenic resistance in Pseudomonas fluorescens strain MSP3.

Pseudomonas fluorescens MSP3 isolated from sea water was resistant to arsenate. This bacterium harbored no plasmids, indicating that arsenic resistance was chromosomally encoded. The chromosomal DNA from MSP3 when transformed onto Escherichia coli DH5alpha using pBluescript exhibited resistance to sodium arsenate and sodium arsenite. Three clones MSA1, MSA2, and MSI3 containing the ars genes were obtained and further subcloning resulted in three fragments of size 2.2, 2.6, and 2.1 kb for pMSA11, pMSA12, and pMSI13, respectively, which contained the genes arsRBC of the arsenic operon. An efflux mechanism of detoxification was observed which was ATP dependent. The resistance mechanism was encoded from a single operon which consisted of an arsenite inducible repressor that regulates the expression of arsenate reductase (ars C) and inner membrane associated arsenite export system encoded by ars B. The chromosomal operon was cloned, sequenced, and found to consist of three cistrons, named as ars R, ars B, and ars C. Southern hybridization and mating experiments confirmed the functioning of the ars genes in the operon, thereby conferring increased resistance to sodium arsenate and sodium arsenite.

Adenosine Triphosphatases↗