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Biomedical subjects

V Nair

Publications and source records attributed to V Nair.

At least 19 recordsLinked to original sources

Concurrent-schedule performance in dairy cows: persistent undermatching.

Performance of dairy cows responding under concurrent variable-interval variable-interval schedules of food delivery was examined, with results analyzed in terms of the generalized matching equation. In Experiment 1, bias measures indicated that crushed barley was preferred over meatmeal when these foods were available under the alternative schedules. For whole-session data, substantial undermatching of response and time-allocation ratios to obtained reinforcement ratios was evident. Postreinforcement pause time ratios approximately matched obtained reinforcement rates. Subtracting these times from total time-allocation values yielded net time-allocation ratios that undermatched obtained reinforcement ratios to a greater degree than did whole-session time-allocation ratios. In Experiment 2, substantial undermatching was evident when the same foods (hay for 2 cows, crushed barley for 2 others) were available under the alternative schedules. Food-related activities and other defined behavior not related to food were quantified by direct observation, and were found to occupy a substantial proportion (roughly 40% to 80%) of experimental sessions. Subtracting the time spent in these activities from the time allocated to each component schedule did not reduce the degree of undermatching obtained. Across all conditions in both experiments, slopes of regression lines relating behavioral outputs to environmental inputs characteristically were below 0.6, which agrees with prior findings and suggests that, contrary to suggestions in the literature, undermatching in dairy cows is not the result of using different foods under alternative schedules or differential pausing under those schedules.

Animals

Antiviral activities of isometric dideoxynucleosides of D- and L-related stereochemistry.

In summary, many isomeric analogs of ddNs of both D-related and L-related absolute stereochemistries have been synthesized and evaluated in vitro for their antiviral activities. A few of these compounds exhibit potent antiviral activity and, interestingly, belong to both the D and L families. The synthetic methodologies developed will allow accessibility to many more novel modified nucleosides. While some structure-activity relationships are emerging from this work, it is clear that these chiral isomeric nucleosides have opened a new chapter in the field of antiviral nucleosides.

Animals

Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol.

4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol (IsoddA) is the most antivirally active member of a novel class of optically active isomeric dideoxynucleosides in which the base has been transposed from the natural 1' position to the 2' position and the absolute configuration is (S,S). IsoddA was active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5-fluoro-2'-deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction of activity was observed with clinical isolates resistant to zidovudine. An IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of increasing concentrations of IsoddA. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in vitro; however, it lacked substantial selective activity in an in vivo HBV model. IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse transcriptase, with a Ki of 16 nM. The cytotoxicity 50% inhibitory concentrations of IsoddA were greater than 100 microM for CEM, MOLT-4, IM9, and the HepG2-derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 microM for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase

Interpretation of the roles of adenylosuccinate lyase and of AMP deaminase in the anti-HIV activity of 2',3'-dideoxyadenosine and 2',3'-dideoxyinosine.

Some 2',3'-dideoxynucleotides, of importance in the enzymology of the anti-HIV compounds, ddA and ddI, have been synthesized and purified by ion-exchange chromatography. 2',3'-Dideoxyadenylosuccinate, an intermediate in the pathway of ddI to ddATP, is converted to ddAMP by AMPS lyase at 1.85% of the efficiency of the natural substrate, adenylosuccinate. Interestingly, ddAMP and other 2',3'-dideoxygenated nucleotides are not substrates for AMP deaminase, another relevant enzyme in the conversion of ddA to ddATP via ddI.

AMP Deaminase

New hypoxanthine nucleosides with RNA antiviral activity.

A series of novel C-2 functionalized hypoxanthine and purine ribonucleosides have been synthesized and evaluated against exotic RNA viruses of the family or genus alpha, arena, flavi, and rhabdo. Both specific and broad-spectrum antiviral activities were discovered but only with hypoxanthine nucleosides.

Animals

Inhibition of mammalian adenosine deaminase by novel functionalized 2',3'-dideoxyadenosines.

2',3'-Dideoxyadenosine (ddA) analogues with a variety of functionalization at the 2-position have been synthesized by a combination of thermal, photochemical and metal-mediated methodologies. These compounds are either totally resistant to deamination by mammalian adenosine deaminase (ADA) or are very poor substrates of ADA. They are competitive inhibitors of this enzyme.

Adenosine Deaminase Inhibitors

Mild tardive dyskinesia: an 8-year follow-up study.

The authors re-examined 20 patients who were found to exhibit mild tardive dyskinesia (TD) involving only one body area in 1980. Of these, 11 still showed TD of the same degree, whereas 4 had no TD and 5 aggravated TD. The authors conclude that mild TD involving one body area should be included in prevalence studies and that Schooler & Kane's definition of minimal manifestation of TD should be extended to include these patients.

Aged

A comparison of severe tardive dystonia and severe tardive dyskinesia.

The authors present a demographic study comparing tardive dystonia with severe tardive dyskinesia (TD) patients. Tardive dystonia was more common among young men, while severe TD was more common in older women. Neuroleptics were distributed equally in both groups before the onset of the movement disorders. Drug-free periods were common in the history of severe TD than in tardive dystonia patients.

Antipsychotic Agents

The association of tardive dyskinesia and pseudoparkinsonism.

1. A survey of 315 chronic inpatients for the presence of extrapyramidal side effects indicates that 58.7% of the patients had no evidence of extrapyramidal side effects, 28.6% had tardive dyskinesia (TD) alone, 8.9% had pseudoparkinsonism and 3.8% had a combination of both. 2. Women seemed to exhibit more side effects. 3. Aging was another factor associated with a higher risk for the appearance of extrapyramidal side effects. 4. Affective disorder patients carried more risk than patients with schizophrenia. 5. The low prevalence of the combined TD and pseudoparkinsonism may be related to several factors. The possible explanations are explored and discussed. These patients present a therapeutic dilemma.

Adult

The chemistry of lipid peroxidation metabolites: crosslinking reactions of malondialdehyde.

Malondialdehyde reacts readily with amino acids to form adducts containing vinylogous amidine linkages. Crosslinking reactions between nucleic acid bases and amino acids induced by malondialdehyde also have been investigated. The physical data obtained for the adducts provide structural information on the possible mode of crosslinking of proteins and nucleic acids induced by this lipid metabolite.

Chemical Phenomena

Early versus late onset psychosis and tardive dyskinesia.

Patients with late-onset psychosis (defined as psychosis requiring hospitalization at age 45 or more, n = 20) were compared with early-onset psychosis patients (defined as psychosis requiring hospitalization at age 25 or less, n = 56) for the prevalence of tardive dyskinesia (TD). Late-onset psychosis patients were found to have significantly more TD (p less than 0.01), which was more severe (p less than 0.05) and developed in a relatively shorter period of neuroleptic treatment (p less than 0.001), than patients with early-onset psychosis. In addition, TD patients (irrespective of early or late onset of neuroleptic treatment) were found to show a preponderance of drug-free periods (p less than 0.01) in their past neuroleptic history, more so than non-TD patients. Our findings indicate that late-onset psychosis should be considered to be a risk factor for the development of TD.

Adult

Prevalence of tardive dystonia.

Tardive dystonia is a rare late-onset side effect of neuroleptics. This paper presents a prevalence study of 351 inpatients conducted in our hospital. Seven patients (2%) were found to suffer from this condition. The majority were found to be young and had received neuroleptics for a variable number of years before the onset of the dystonia. In general, treatment of this condition is disappointing.

Adult

Prophylaxis and the lithium ratio in bipolar patients.

Thirty-five bipolar outpatients treated with lithium carbonate were followed for up to 5 years with the aim of studying the relation of the lithium ratio (LR) and its predictive value. Only male responders were found to have higher LR than male nonresponders. No difference was found between the mean LR of men and women, as a group. Aging also had no effect on LR. Positive family history of affective disorders was correlated with high LR, irrespective of response.

Adult