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Biomedical subjects

N G Rao

Publications and source records attributed to N G Rao.

At least 19 recordsLinked to original sources

Metabolic aspects of the toxicology of mixtures of parathion, toxaphene and/or 2,4-D in mice.

The effects of mixtures of parathion (PA;5 mg kg-1), toxaphene (TOX; 50 mg kg-1)and/or 2,4-dichlorophenoxyacetic acid (2,4-D; 50 mg kg-1) on the hepatic mixed-function oxygenase (MFO) system were studied in ICR male mice (21-24 g) by oral intubation daily for 7 days. In general, TOX and TOX-containing mixtures were found to induce the metabolism of amidopyrine (21-52%), aniline (58-72%), phenacetin (239-307%), pentobarbital (104-148%) and benzo[a]pyrene (143-304%) in the 9000 g liver supernatants and to increase the hepatic cytochrome P-450 contents (57-80%). Furthermore, the TOX pretreatment was effective in enhancing the biotransformation of PA or paraoxon (PO) in the supernatants. This enhancement was not altered significantly by 5 mM EDTA. Although TOX increased the aliesterase activity in the serum and liver homogenates and supernatants by 31-158%, the activity of paraoxonase was not affected in these preparations. The TOX-induced increase in the metabolism of PA or PO was, at least in part, associated with the MFO system, and paraoxonase did not have significant involvement in the increase. These findings suggest that the toxicity of the PA + TOX mixture would be lower than that of PA, as TOX has the ability to increase the biotransformation of PA, as well as of PO, and the levels of aliesterase, thereby providing a pool of noncritical enzymes for the binding of PO. Because of these properties of TOX, it is anticipated that the toxicity of the PA + TOX + 2,4-D mixture also would be lower than that of PA.

2,4-Dichlorophenoxyacetic Acid

Toxicity of mixtures of parathion, toxaphene and/or 2,4-D in mice.

The toxicity of the mixtures of parathion (PA), toxaphene (TOX) and/or 2,4-dichlorophenoxyacetic acid (2,4-D) was studied in ICR male mice (21-24 g) by oral intubation, in corn oil, daily for up to 14 days. On Day 15, the exposure was discontinued, and animals were monitored for an additional period of 7 days for the possible reversibility of the toxicity. The body weight gain decreased with the mixtures, as well as with the individual agricultural chemicals (ACs), during the 14-day period. The cholinesterase (ChE) activity in the serum and brain was inhibited in the animals of the groups of PA (1-10 mg kg-1) and PA (5 mg kg-1)-containing mixtures. TOX (50-200 mg kg-1) caused initial inhibitory effects of 20-65% on the serum ChE (Day 1) before producing increases of 53-64% in the enzyme activity by Day 15, with little effects on the brain ChE levels. 2,4-D (50-200 mg kg-1) resulted in significantly elevated levels of the serum ChE, with substantial decreased in the brain ChE activity. The serum glutamic pyruvic transaminase level was up (38-630%) in TOX (50 mg kg-1), 2,4-D (50 mg kg-1) or their mixture group. No pathological changes at the light microscopic level in the brain and liver were noticed. TOX and TOX-containing mixtures significantly increased the liver/body weight ratio and decreased the pentobarbital (60 mg kg-1, i.p., in saline)-induced sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

2,4-Dichlorophenoxyacetic Acid

Mandibular canine index--a clue for establishing sex identity.

A preliminary study for establishing sex identity by Mandibular Canine Index is described. Seven hundred and sixty six individuals from a South Indian population of either sex, ranging in age from 15 to 21 years, with fully errupted, healthy and non-worn mandibular permanent canines were studied. The data collected was analysed statistically. Accurancy of sex determination identity was found to be 84.3% in the male and 87.5% in the female. The method is simple and inexpensive to conduct and therefore can be applied in Forensic Odontology, as a method for establishing sex identity.

Adult

Toxicological evaluation of a poisoning attributed to ingestion of malathion insect spray and correlation with in vitro inhibition of cholinesterases.

A 24-year-old Caucasian male was found dead from unknown causes at his farm home. At the scene, partially filled bottles of ORTHO Malathion 50 Insect Spray and CLOROX bleach were found. At the time of autopsy, a strong odour of a petroleum based product was prominent in the small intestine and in the liquid stool. A similar odour was also present in the liquids of both bottles. Generalized visceral and vascular congestion with oedema in various tissues was markedly present. Toxicological analysis of the gastric contents, intestinal contents, bile and liquid samples from the malathion and bleach bottles revealed the presence of malathion in the concentrations of 2.1 g/kg, 98 g/kg, 570 mg/l, 54% and 11%, respectively. In the blood and urine, malathion was not detected. Xylenes and other common volatile components of the spray were detected in the liquids from the bottles and in the gastric and intestinal contents. The ability of the blood and bile samples to inhibit, in vitro, rat serum cholinesterase and electric eel acetylcholinesterase was consistent with their malathion concentrations as the bile inhibited both enzymes, while the blood did not. These findings conclude that the death was associated with the ingestion of a commercial malathion insect spray.

Acetylcholinesterase

Costal cartilage calcification pattern--a clue for establishing sex identity.

Radiological study of costal cartilage calcification patterns in establishing the sex identity is conducted in Southern Indians. Three major patterns of calcification capable of establishing sex identity were noticed. Calcification was not observed below the ages of sixteen years in the female and twenty years in the male. This, though seriously limits the applicability of the method to age groups of sixteen and twenty years and above in the female and male sexes respectively, the ease, rapidity and relative inexpensiveness of the procedure in both living as well as dead and decomposed, requiring little expertise, recommends its use especially where a forensic expert is readily not available.

Adolescent

Two tricyclic antidepressant poisonings: levels of amitriptyline, nortriptyline and desipramine in post-mortem biological samples.

Two deaths due to amitriptyline and desipramine overdoses are reported. The first case deals with a 20-year-old Caucasian male who was found dead at his residence. Toxicological analysis of the blood, urine, liver and kidney revealed the presence of amitriptyline (1.7 mg/l, 0.13 mg/l, 36.0 mg/kg and 98.0 mg/kg) and nortriptyline (0.66 mg/l, 0.74 mg/l, 12.0 mg/kg and 37.0 mg/kg). The gastric content contained only 220 mg of amitriptyline. The urine also contained norverapamil, which was consistent with previous verapamil therapy. The second case involved a 19-year-old Caucasian male who attempted suicide earlier and was on desipramine medication. The blood, urine, liver and gastric content disclosed the presence of desipramine in the concentrations of 14.2 mg/l, 33.7 mg/l, 112.5 mg/kg and 180 mg, respectively. The levels of these tricyclics analyzed by high pressure liquid chromatography were in agreement with the levels reported in the literature. Though with the amitriptyline poisoning no significant anatomic changes were noted, the desipramine-caused death was further supported by the multisystem vascular congestion and ischemic changes consistent with cardiopulmonary failure.

Adult

Poisoning associated with potassium.

A suicidal poisoning by intravenous administration of concentrated solution of potassium (K+) (chloride) is described in the study. A 30-year-old Caucasian female health professional was found dead in a motel. An intravenous needle was found inserted in the antecubital area in a right arm vein of the deceased. Attached to the needle, by a flexible tubing, was a 50 ml syringe four-fifths full of a clear liquid. Autopsy on the victim revealed pulmonary oedema and congestion. A routine toxicological analysis of biological samples ruled out the possibility of a drug overdose. However, the liquid from the syringe contained 1468 mmol of K+/l. Chloride ions were also present in high concentration in the liquid. The concentrations of K+ in the clear plasma and vitreous humour were 54 and 9.2 mmol/l respectively. It is suggested that the elevated level of K+ in the plasma or vitreous humour does not indicate necessarily a death due to the electrolyte. The evidence in this case is circumstantial and apparently can be expected to be so in any case where death is due to the intravenous infusion of a concentrated K+ solution.

Adult

Toxicity of 1-phenylcyclohexene and its interaction with phencyclidine.

The toxicity of 1-phenylcyclohexene (PC), a pyrolysis product of phencyclidine (PCP), and its interaction with PCP were evaluated. The ip LD50 of PC in Swiss male mice was 22 mmol/kg. Treatment of mice with PC at 2.2 mmol/kg/day, ip, for up to 7 days increased the liver/body weight ratio, which returned to normal within 7 days after PC withdrawal. Increases of 32% in serum glutamic-oxalacetic transaminase (SGOT) and 94% in serum glutamic-pyruvic transaminase (SGPT) were observed within 4 hr following the initial (Day 1) dose of PC. Smaller increases in the SGOT activity continued following Day 2 and 3 PC administrations. The SGPT activity remained elevated after these treatments. Activities of both enzymes, however, returned to normal within 24 hr following daily PC injections. No pathologic changes were observed in liver, brain, spleen, kidneys, and lungs with light microscopy. PC treatment for 4 days at 2.2 or 4.4 mmol/kg produced proliferation along with dilatation and fragmentation of the endoplasmic reticulum in liver. Scattering of ribosomes in the cytoplasm and dilatation of rough-surfaced cisternae were prominent at the higher dosage. Pretreatment of animals for 4 days with PC (1.1, 2.2, and 4.4 mmol/kg, ip) decreased pentobarbital- (60 mg/kg) induced sleeping time by 27, 64, and 80% and lowered PCP- (16.4 mumol/kg) stimulated locomotor activity by 18, 28, and 41%, respectively. Pretreatment of animals with PC for 1 hr inhibited (ED50: 2.3 mmol/kg) the PCP-induced locomotion. These results indicate that the PC treatment during a 7-day period produces some undesirable effects on liver function, which are reversible on its discontinuation. However, PC also weakens toxic effects of PCP.

Animals

Influence of phencyclidine on the translocation of pentobarbital in mice.

The influence of phencyclidine (PCP) on the tissue distribution of pentobarbital in male Swiss mice (20-25 g) was investigated. Animals pretreated with PCP (179 mumol/kg/day) for 4 days, i.p., were administered pentobarbital (60 mg/kg, i.p.) 24 h after the PCP injection, sacrificed at various time intervals, and tissues (serum, brain, liver and kidney) were collected. Pentobarbital levels in tissues were determined by the gas liquid chromatography. When compared to the control group, PCP treatment decreased the pentobarbital level by 68% in liver and increased the level by 97% in kidney at 45 min post-injection. No significant change in serum and brain pentobarbital level was noted with either group. These data indicate that PCP influences the translocation of pentobarbital.

Animals

An isocratic high-pressure liquid chromatographic determination of naproxen and desmethylnaproxen in human plasma.

An isocratic high-pressure liquid chromatographic method for the determination of naproxen and its desmethyl metabolite in human plasma is presented. A reversed-phase octadecylsilane column was utilized with a mobile phase consisting of 55% methanol and 45% 0.10 M acetate buffer, pH 5.0. A spectrofluorometric detector with an excitation wavelength of 253 nm and a band pass filter provided high sensitivity with no interference from normal plasma constituents. The reproducibility and precision of the method were shown by analysis of spiked samples containing 2.5-70 micrograms/ml of plasma.

Chromatography, High Pressure Liquid

High-pressure liquid chromatographic determination of ibuprofen in plasma.

A high-pressure liquid chromatographic method is presented for the determination of ibuprofen in human plasma. Ibuprofen is extracted from plasma acidified with 1.0 M phosphoric acid using hexane containing p-phenylphenol as an internal standard. A reversed-phase octadecylsilane column was used with a liquid phase of 65% methanol and 35% 0.10 M acetate buffer (pH 5.0). A spectrofluorometric detector with an excitation wavelength of 253 nm and a band pass filter (230--420 nm) provided a detectable peak for 1 microgram of ibuprofen/ml of plasma. The effect of the pH and molarity of the mobile phase on the capacity factor was studied.

Anti-Inflammatory Agents, Non-Steroidal

The role of hepatic microsomal enzymes in the modulation of phencyclidine-induced toxicity.

The LD50 of phencyclidine (PCP, 234 mumol/kg, i.p.) in male Swiss mice decreased by 62% in animals pretreated with 2-diethylamino-2,2-diphenylvalerate hydrochloride (SKF-525A, 40 mg/kg), and increased by 74% and 20% in animals pretreated with sodium phenobarbital (75 mg/kg), and 3-methylcholanthrene (70 mg/kg), respectively, No Significant change in the LD50 was observed with cysteine or diethylmaleate pretreatment. The treatment with PCP at 179 mumol/kg/day i.p. for 7 days resulted in body weight decrement in the first 2 days and gradual increment thereafter. The increase was only 33% of the control group. The food intake was also lower in the PCP treated group of animals. PCP withdrawal led to an increase in food intake as well as body weight at a normal rate. The ratio of liver weight to body weight was not significantly higher than that of control during the treatment period. The administration of PCP for 7 days did not alter the activities of liver function enzyme markers. However, within 12 h of the initial PCP treatment a 85% increase in activity of serum glutamicoxalacetic transaminase was observed. Later the enzyme activity reached close to normal levels. No liver lesions at the light microscopic level were observed. Treatment of mice for 4 days with PCP (179 mumol/kg) caused no significant change in pentobarbital sleeping time.

Animals

Toxicological findings in a multi-drug death involving propoxyphene, caffeine, phenacetin, acetaminophen and salicylate.

The toxicological findings of a multi-drug related fatal poisoning are described here. A 35-year-old Caucasian male found dead on the kitchen floor was a known user of abused drugs and had been taking aspirin alone or in combination with phenacetin and caffeine for the relief of joint pains. The gross examination of the organs at autopsy revealed slight grooving of the uncus and various stages of necrosis in the renal papillae. Histological examination confirmed the gross appearance of pulmonary congestion and edema, cerebral edema and interstitial nephritis of the tubules. Toxicological evaluation of the blood and urine samples disclosed the presence of propoxyphene (51 and 250 mg/l), salicylate (185 and 2750 mg/l), caffeine (16 and 37 mg/l), and phenacetin (9.6 and 20 mg/l). Furthermore, acetaminophen also was present in the plasma (54 mg/l) and urine. A gas liquid chromatographic method for simultaneous analysis of phenacetin and caffeine utilizing a nitrogen phosphorus detector was proposed.

Acetaminophen