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Biomedical subjects

R K Srivastava

Publications and source records attributed to R K Srivastava.

At least 19 recordsLinked to original sources

Scavenger-receptor-mediated delivery of daunomycin elicits selective toxicity towards neoplastic cells of macrophage lineage.

Transformed cells of macrophage lineage such as J774A.1, P388D1 and IC21 take up and degrade a conjugate of the antineoplastic drug, daunomycin, with maleylated BSA with high efficiency and saturation kinetics through the scavenger receptors expressed on the surface of these cells. By contrast, transformed cells of non-macrophage lineage, namely L929, EL4, Bowes melanoma and CHO (Chinese-hamster ovary), do not take up and degrade the conjugate, indicating that these cells are scavenger-receptor-deficient. In the conjugated form, about 0.1 microM-daunomycin cause 50% inhibition in the uptake of [3H]thymidine by the receptor-bearing J774A.1 cells, whereas the receptor-deficient Bowes-melanoma cells are not affected. Free daunomycin (0.1 microM) does not significantly affect the uptake of [3H]thymidine by either cell type. Treatment of cells derived from intraperitoneal tumours induced in BALB/C mice by J774A.1 cells with 0.4 microM-daunomycin in the conjugated form for 5 h abolished their ability to form tumours in BALB/C mice. By contrast, transplantation of untreated cells or cells treated with free daunomycin under identical conditions led to tumour formation and subsequent death of the BALB/C mice. These results indicate that this modality for selective elimination of scavenger-receptor-bearing neoplastic cells may be useful for the treatment of histiocytic malignancies in which cells of macrophage lineage turn malignant.

Albumins

Changes in polyamines during embryonic development of Atlantic salmon, Salmo salar.

1. Polyamine composition of eggs and alevins from cultured and wild Atlantic salmon, Salmo salar, was compared during early development. 2. Eggs collected from wild stock had higher amounts of bound and free putrescine, spermidine and spermine than those collected from cultured stock. 3. Cadaverine was present in bound form in cultured and wild stocks before and after fertilization, respectively. However, free cadaverine was detected in both stocks throughout development. 4. Atlantic salmon embryos and alevins can synthesize polyamines which could be associated with their growth and development.

Animals

Cerebral palsy.

The clinical pattern and etiology of 544 cases of cerebral palsy were studied retrospectively. Of these cases, 354 (65.1%) were males. Four hundred and ninety seven (91.4%) cases were of spastic type. Hypotonic, ataxic and athetoid cerebral palsy were observed in 5.5, 1.5 and 1.3% cases, respectively. There was one case each of tremor and mixed type. In the spastic group, quadriplegia comprised the maximum number of cases (34.9%). Hemiplegia (28.7%) and diplegia (21.9) were also common. Mental retardation was found in 47.2%, while speech impairment was observed in 37% cases. Other handicaps included visual (9%), seizures (8.8%), and auditory handicap (2.9%). The etiological factors were prenatal in 7.7% cases, natal in 43.8% cases and postnatal in 26.1% cases. More than one etiological factor was observed in 14.5% cases, while in 7.9% cases, no apparent cause could be found.

Cerebral Palsy

Role of soluble factors in immune and normal sera in the control of giardiasis due to Giardia lamblia.

Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non-inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite.

Agglutination

Impact of mass bathing on the water quality of the Ganga River at Haudeshwarnath (Pratapgarh), India--a case study.

This paper reports on the impact of mass bathing on Ganga River water quality on the occasion of the Maha-Shivaratri festival at Haudeshwarnath Ghat situated on the left bank of the River Ganga in the district of Pratapgarh, India. Water samples collected from three sampling points before and after mass bathing were analysed for a total of 17 physico-chemical and seven biological parameters. It was concluded from the results that mass bathing causes a significant change in water quality of the river, which may represent a health hazard to users of the river water.

Baths

Antireproductive effect of a potent LHRH antagonist (Nal-Lys antagonist:antide) during early pregnancy in the rat.

Effects of a potent third generation LHRH antagonist [Nal-Lys antagonist:antide] have been observed during the first half of pregnancy in rats. A daily dose of 40 micrograms or above, when administered from day 8 of pregnancy, suppressed serum progesterone levels within 48 h and by day 12 there was complete absence of live fetuses. Lower doses of antide (10-20 micrograms) reduced progesterone levels in circulation but were unable to induce abortion consistently in all treated rats. Administration of 150 or 300 micrograms of antide once on day 8 suppressed the progesterone levels within 24 h. Only a dose of 300 micrograms was effective in completely interfering with gestation by day 12 with no observable live fetuses.

Animals

Teratogenicity studies of a new potent tetanus vaccine in rabbit (Oryctolagus cuniculus).

Glaxo Laboratories, Bombay, have prepared a potent tetanus vaccine of 250 Lf as a substitute of the previous 5 Lf tetanus vaccine. The safety evaluation of the vaccine has been reported, but the teratogenic potential was not studied. In the experiment reported herein we have studied the teratogenic action of the vaccine in the progeny of rabbits. No congenital anomalies were observed.

Animals

Preclinical toxicity study of a male injectable antifertility agent (styrene maleic anhydride) in rhesus monkeys, Macaca mulatta.

Polymer styrene maleic anhydride dissolved in dimethyl sulphoxide was injected intravasally to rhesus monkeys at the dose levels of 100 mg, 250 mg, and 500 mg in each vas deferens in low, high, and highest dose groups respectively, while control group received 0.5 ml DMSO in each vas deferens. The systemic toxicity study of the implant was carried out for 90 d. There had been no alteration in any of the toxicity parameters, ie, body weight, haematological, biochemical or histopathological, in the test animals as compared to control animals. Hence, it is concluded that the polymer SMA injected at above doses appears to be safe in our experiment.

Animals

Chronic toxicity of styrene maleic anhydride, a male contraceptive, in rhesus monkeys (Macaca mulatta).

A newly developed male contraceptive, styrene maleic anhydride (SMA), was injected in the vas deferens of male rhesus monkeys for safety evaluation at the dose of 100 mg (contraceptive dose, CD), 250 mg (CD x 2.5) and 500 mg (CD x 5.0), and the monkeys were kept under observation for one year. The observed behavioural, haematological, biochemical and histopathological parameters in treated monkeys were comparable to controls. The results suggest the polymer SMA to be safe up to 5 times CD in monkeys.

Adrenal Glands

Maturation of precursor 10Sa RNA in Escherichia coli is a two-step process: the first reaction is catalyzed by RNase III in presence of Mn2+.

A precursor to 10Sa RNA accumulates in an rne mutant. However, the present studies indicate that RNase III is the enzyme that processes this RNA. Cell extracts prepared from an rne mutant failed to cleave p10Sa RNA, whereas E coli wild type, rne and rnp cell extracts processed p10Sa RNA under specific assay conditions that require the presence of Mn2+ but not under the customary conditions used for assaying RNase III. That the p10Sa cleaving activity is solely RNase III was confirmed by comparing the increase in p10Sa and poly(A).poly(U) cleaving activities in a strain harboring a plasmid carrying an RNase III gene as compared to a normal E coli strain. It is of interest that these 2 substrates are cleaved by RNase III efficiently, but under 2 different assay conditions. In all strains tested, with normal or elevated levels of RNase III, RNase III fractionates predominantly with the membrane. Further characterization of the maturation of 10Sa RNA revealed that the processing of 10Sa RNA is a 2 step reaction involving 2 separate activities, both sensitive to heat and proteinase K treatment. The first step is catalyzed by RNase III, and results in the formation of a molecule, p10Sa', which is larger than the mature 10Sa RNA. The second activity catalyzes the conversion of p10S' to 10Sa RNA, and this step does not require a divalent cation. The second activity is not any of the known processing endoribonucleases, RNase III, E or P, but could be a new enzyme having no obligate requirement for a divalent cation.

Endoribonucleases

Long-term toxicity studies of styrene maleic anhydride in rats.

In male Charles Foster rats, polymer styrene maleic anhydride was injected into the lumen of the vas deferens at dose levels of 1.0, 2.5, and 5.0 mg in each vas deferens of Groups II, III, and IV, respectively, while controls (Group I) received 0.03 ml dimethyl sulfoxide in each vas deferens. The rats were observed for 6 months for toxicity. No change in any of the toxicity parameters in test animals as compared to controls was revealed. Hence, the polymer is safe at the doses used within 6 months of injection.

Animals

Safety evaluation of a potent tetanus vaccine (250 Lf) in guinea pigs (Cavia procellus).

A subacute toxicity study of a potent tetanus toxoid (250 Lf) was carried out in guinea pigs. The toxoid was injected subcutaneously at the nape of the neck at dose levels of 1.0, 1.5, and 2.0 ml in Groups II, III, and IV, respectively. In the controls (Group I) 2.0 ml of aluminum phosphate suspension was given in each injection. Periodic evaluations of body weight, food/water intake, general observable behavior, hematology, and blood chemistry in toxoid-injected guinea pigs were similar to those in control guinea pigs. Thus, the toxoid did not cause any side effects up to four times the dose proposed for humans.

Animals

Subacute toxicity of adsorbed 250 Lf tetanus toxoid in rats.

Since the naturally acquired tetanus antitoxin titre in Indian population is mostly less than protective levels, to minimise the incidence of morbidity, Glaxo Laboratories (India) Ltd., Bombay have prepared a single dose potent tetanus vaccine of 250 Lf as compared to 5 Lf previous tetanus toxoid. Subacute toxicity study revealed that this toxoid (250 Lf) injected at different dose levels (1-2 ml/rat/injection x 4) is non-toxic to rats.

Animals

Safety evaluation of a male injectable antifertility agent, styrene maleic anhydride, in rats.

Injection of a polymer, styrene maleic anhydride (SMA), into the lumen of the vas deferens of rats, was observed to have effective and reversible contraception. The safety evaluation of the polymer, for 90 days, was carried out in Charles Foster male rats. There have been no significant changes in any of the toxicity parameters in the test animals as compared to the control animals. Hence, it is concluded that the compound is non-toxic to rodents.

Animals

Non-specific cardiovascular depressant effect of methyl isocyanate (MIC) in rats.

Methyl isocyanate (MIC) either inhaled (5, 10 mg/lit) or administered by intravenous (5, 10, 28 mg/kg) or subcutaneous (1300, 1500 mg/kg) routes produced a dose dependent fall in blood pressure (BP) and heart rate (HR) in anaesthetised rats. Higher doses (10 mg/lit inhalation, 10 & 28 mg/kg i.v., 1500 mg/kg s.c.) increased the lung body weight index (LBI) and tracheobronchial resistance (TBR) concomitant with gross pulmonary damage and edema. However, lower doses (5 mg/lit inhalation, 5 mg/kg i.v., 1300 mg/kg s.c.) produced the cardiovascular depressant effect without affecting LBI, lung morphology and TBR. The effects of MIC on BP, HR and TBR were not counteracted by muscarinic, histaminic and 5-HT receptor blockers and by vagotomy. Studies with hydrolysis products of MIC showed that relatively large doses of methylamine (MA) and dimethylurea (DMU) (i.v.) produced cardiovascular depressant effects, without affecting the LBI & TBR. The results indicate that the cardiovascular depressant effect of MIC may not be entirely a sequel to its effect on respiratory organs, release of vasoactive substances or its hydrolysis products. A non-specific cardiovascular depressant effect of MIC is suggested.

Airway Resistance