PubMed Health⌕ Search

Biomedical subjects

S Kalyanasundaram

Publications and source records attributed to S Kalyanasundaram.

13 recordsLinked to original sources

Nonclinical toxicology study of recombinant-plasmid DNA anti-rabies vaccines.

The absence of standard guidelines from National and International regulatory agencies for the safety evaluation of biotechnology products challenges the ingenuity of toxicologists. At present, the development of standard pre-clinical toxicology protocols for such products is on an individual case basis. The present investigation is an attempt to evaluate the safety profile of the first indigenously developed DNA based anti-rabies vaccine in India. The test compounds were DNA rabies vaccine [DRV (100 microg)] and combination rabies vaccine (CRV (100 microg DRV and 1/50 dose of cell culture vaccine)), intended for clinical use by intramuscular route on 1, 7, 14 and 28 day. As per the regular mandatory requirements, the study has been designed to undertake acute (single dose--10 days), sub-chronic (repeat dose--28 days) and chronic (intended clinical dose--120 days) toxicity tests using three dose levels viz. therapeutic, average (2 x therapeutic dose) and highest dose (10 x therapeutic dose) exposure in Swiss Albino mice. The selection of the rodent model viz. Swiss Albino mice is based on affinity and rapid higher antibody response during the efficacy studies. Apart from physical, physiological, clinical, hematological and histopathology profiles of all target organs, the tier-I immunotoxicity parameters have also been monitored. There were no observational adverse effects even at levels of 10x therapeutic dose administration of DRV and CRV. The procedure also emphasizes on the designing of protocols for the products developed by recombinant technique.

Animals↗

The Yelandur study: a community-based approach to epilepsy in rural South India--epidemiological aspects.

Data on the epidemiology of epilepsy in a rural community in a developing country would be of value in planning a decentralized management of this malady in its early stages commensurate with available local resources. A detailed screening instrument covering various seizure types was used by trained paramedical workers in a door-to-door survey of a population of 64,963 in rural South India. The prevalence period was from 1 April 1990 to 31 March 1991. The crude prevalence rate per 1000 for active epilepsy was 4.38 for males, 3.40 for females and 3.91 for both. The minimum and maximum prevalence rates, the latter computed from a validation sample, were 3.91 and 4.63 for active epilepsy; 0.28 and 0.77 for inactive epilepsy and 4.19 and 5.41 for life-time prevalence. In addition, corresponding figures for hot-water epilepsy, a type of reflex epilepsy peculiar to this area, were 2.49 and 2.99 for active phase; 0.35 and 0.85 for inactive phase and 2.85 and 3.83 for life-time prevalence. The incidence rate for epilepsy was 49.3 per 100,000, the same as in developed countries. These data do not support the concept that the prevalence of epilepsy in developing countries is twice that in the developed world. However, the role of local/regional variations should be borne in mind before extrapolating the figures to an entire country.

Adolescent↗

A finite element model for predicting the distribution of drugs delivered intracranially to the brain.

Drug therapy to the central nervous system is complicated by the presence of the blood-brain barrier. The development of new drug delivery techniques to overcome this obstacle will be aided by a clear understanding of the transport processes in the brain. A rigorous theoretical framework of the transport of drugs delivered locally to the parenchyma has been developed using the finite element method. Magnetic resonance imaging has been used to track the transport of paramagnetic contrast markers in the brain. The information obtained by postprocessing spin-echo, T1-weighted, and proton density images has been used to refine the mathematical model that includes realistic brain geometry and salient anatomic features and allows for two-dimensional transport of chemical species, including both diffusive and convective contributions. In addition, the effects of regional differences in tissue properties, ventricular boundary, and edema on the transport have been considered. The model has been used to predict transport of interleukin-2 in the brain and study the major determinants of transport, at both early and late times after drug delivery.

Animals↗

Utilization of tyrosine and tryptophan for protein synthesis by undernourished developing rat brain.

Incorporation of tracer doses of radiolabeled tryptophan and tyrosine into brain proteins was investigated in rats malnourished during gestation and lactation. Age and time dependent increases in the radioactivity was observed in the whole homogenate and in the TCA insoluble fraction. Protein malnourished rats showed increased incorporation of tryptophan and tyrosine. However the diet restricted (Pair-fed) animals showed increased incorporation of tyrosine only. The increased incorporation may probably be due to changes in the pool size of the amino acids and effective recycling of the amino acids. The enhanced utilization in protein synthesis may also probably offer a mechanism for conservation of these amino acids.

Animals↗

Free amino acid levels in undernourished developing rat brain.

Free amino acid levels in the brains of young ones born to mothers fed a 20% protein diet ad libitum (well nourished), 7.5% protein diet ad libitum (protein restricted) and a 20% protein diet in restricted amounts (pair-fed) were investigated during brain development in the present study. The dietary protein was obtained from a cereal-legume mixture. Protein restricted animals showed increases in the levels of taurine, glycine and glutamic acid and decreases in the concentrations of methionine, leucine, isoleucine, and GABA. The pair-fed animal showed increases only in glutamic acid and glycine and a decrease only in the levels of GABA. The significance of these observations is discussed.

Aging↗

Effect of undernutrition on tryptophan and tyrosine hydroxylases in the developing rat brain.

Rats born to well-fed mothers (20% protein diet ad libitum), protein-restricted mothers (7.5% protein diet ad libitum) or pair-fed with protein-restricted mothers were killed on days 0, 7, 14, 21, 28 and 35 and activities of the two enzymes of neurotransmitter synthesis, tryptophan-5-hydroxylase (EC 1.14.16.4) and tyrosine hydroxylase (EC 1.14.16.2) were assayed. Enzyme activities in normal animals were low at birth and progressively increased to reach adult levels by day 15. Protein-restricted and pair-fed animals also showed a similar pattern. However, significantly higher activities were observed from day 15 onwards in both experimental groups.

Animals↗

Single daily dose chlorpromazine therapy in psychosis. An evaluation.

A double blind study was undertaken to compare the efficacy of a single bedtime dose of chlorpromazine (300 mg) with divided doses of the same drug (100 mg, thrice daily). Brief Psychiatric Rating Scale (BPRS) and Nurses' Observation Scale for Inpatient Evaluation (NOSIE) were administered to 80 acutely psychotic patients who took part in the study. Thirty-one patients in the experimental and 29 in the control group completed this 3-week trial. It was observed that there were no statistically significant differences between the two modes of treatment. Drowsiness was seen more often in the single bedtime schedule. Postural hypotension was observed in both patient groups. The implications of single night-time medication in psychotics is discussed.

Adolescent↗

Effect of dietary protein and calorie deficiency on tryptophan levels in the developing rat brain.

The pattern of development of brain tryptophan in the rat was studied in the progeny of mothers fed a 7.5% protein diet ad lib., a 20% protein diet ad lib. and those fed a 20% protein diet pair-fed with mothers who received the 7.5% protein. The pattern of development was similar in all three groups. Starting with a high brain tryptophan content at birth, all animals showed a progressive reduction during the next 3 weeks. However, tryptophan levels at birth were several fold higher in the brains of pups born to mothers receiving either the low protein diet fed ad lib. or those born to mothers who received the 20% protein diet in restricted amounts. From the 14th day after birth, tryptophan concentration of brain in undernourished pups was significantly lower until the 35th day. The implications of this finding are discussed.

Aging↗

Coacervate microspheres as carriers of recombinant adenoviruses.

The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 microM in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner.

Adenoviridae↗