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2.
Indian J Med Microbiol ; 37(3): 393-400, 2019.
Article in English | MEDLINE | ID: mdl-32003339

ABSTRACT

Context: Dengue virus (DENV) causes acute febrile illness in tropical and subtropical countries. In India there is a steady increase in incidence since 1950s which could be attributed to emergence of new serotype or lineage\clade shifts in circulating DENV. Aims: We aimed to perform molecular characterisation and phylogenetic analysis on samples from the recent outbreak (August-October 2017). Settings and Design: Retrospective epidemiological analysis of dengue outbreak. Subjects and Methods: Samples positive for non-steroidal 1 antigen by enzyme-linked immunosorbent assay (n = 147) were included. The study was approved by our institute ethics committee (JIP/IEC/2018/496). Five hundred and eleven base pair of capsid and pre-membrane encoding genes (CprM) region was amplified using Lanciotti primers, followed by second round of polymerase chain reaction using serotype specific primers. Samples which were positive by second round (n = 68) were sequenced and genotyped using Basic Local Alignment Search Tool analysis and phylogenetic tree was constructed by MEGA7 software. Results: Phylogenetic analysis of CprM sequences identified all 4 serotypes in circulation during this outbreak. We observed both single (n = 50) and concurrent infections (n = 18), with DENV4 as the major contributor (64%). Within Genotype I of DENV4 we observed a distinct new clade (Clade E) which was 2.6% ± 0.9%-5.5% ± 1.1% divergent from the other clades. Among the concurrent infection, DENV 4 and DENV 2 combination was observed to form the majority (77.8%). Conclusions: Overall this study documents the emergence of DENV4 as the major serotype in circulation, replacing DENV1, 2 and 3 which had been previously reported from Tamil Nadu and Puducherry. This substantiates the need for continuous monitoring in endemic countries like India, where such data may impact the formulation of vaccine policy for dengue.


Subject(s)
Dengue Virus/genetics , Adolescent , Adult , Child , Child, Preschool , Dengue Virus/classification , Humans , India , Middle Aged , Phylogeny , Retrospective Studies , Serogroup , Young Adult
3.
Neurotox Res ; 34(3): 597-612, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30006683

ABSTRACT

Many studies reported the neuroprotective effects of angiotensin II type 1 receptor (AT1R) antagonists in Parkinson's disease (PD). However, the role of AT1R blockade on astroglial, in turn, dopaminergic functions in chronic PD is still to be studied. In the present study, telmisartan (TEL; 3 and 10 mg/kg/day; p.o), was used to study the effects AT1R blockade on astrocytic and dopaminergic functions in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinsonism (250 mg/kg, i.p, in 10 equally divided doses at 3.5 days interval) in C57BL/6 J mice. TEL significantly downregulated glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS), TNFα and IL1ß expressions and nitric oxide (NO) content. Significant upregulation glial cell derived neurotrophic factor (GDNF) expression and increased glutathione (GSH) content reveal the ameliorating effects of TEL on astroglial functions. On the other hand, TEL upregulated tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) expressions. Finally, TEL improved dopamine and its turnover and restored locomotor performance. Present experiment reveals that TEL has the potential to alleviate astroglial functions, apart from restoring dopaminergic functions, at least in part. To conclude, TEL may be a better disease-modifying therapeutic regimen in the management of Parkinsonism, acting primarily via astroglial-dopaminergic functions.


Subject(s)
Astrocytes/drug effects , Dopamine/metabolism , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/pathology , Telmisartan/pharmacology , Telmisartan/therapeutic use , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Animals , Chronic Disease , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Disease Models, Animal , Gene Expression Regulation/drug effects , Glutathione/metabolism , Male , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Nitric Oxide/metabolism , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/physiopathology , Psychomotor Disorders/drug therapy , Psychomotor Disorders/etiology , Substantia Nigra/drug effects , Substantia Nigra/metabolism , Walking
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