Biochemical studies on the toxicity of 1, 1'-dimethyl-4, 4'-bipyridylium dichloride in the rat.

The effect of intraperitoneal administration of lethal dose (50 mg/kg) of paraquat on the microsomal cysteine levels in the plasma, liver and lung of adult male Wistar rats has been investigated using Rank Chromaspek amino acid analyzer. The microsomal alanine levels were also determined to help in assessing the extent of paraquat interference with cellular protein. DL-Buthionine-[S,R]-Sulfoximine (BSO) and Diethyl maleate (DEM) were used to potentiate the toxic effect of the bipyridyl. The microsomal cysteine levels were significantly (P < or = 0.05) depressed in the plasma, liver and lung of the paraquat-treated rats compared with the saline-injected group but the alanine levels were not similarly affected. Probably, paraquat poisoning interferes specifically with the cellular cysteine content in the rat. These findings could provide a valuable information on the biochemical mechanism of paraquat intoxication.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on contractile responses in isolated rat aorta.

The vascular effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a meperidine analog, were studied in vitro on ring preparations of rat aorta for the purpose of characterizing its mode of action. Isometric contractions were evaluated under standard organ bath conditions. Exposure to MPTP (10(-12)-1.6 x 10(-8) M) did not affect basal tension but did cause dose-dependent relaxation of rings precontracted by 10(-7) M noradrenaline (NA) and was ineffective against 30 mM K+ contractions. Removal of endothelium did not significantly modify the relaxation responses. In 10(-5) M NA-stimulated (but not in 100 mM K(+)-stimulated) rings, MPTP significantly (p < 0.05) attenuated contractile responses to calcium chloride following calcium-free exposure. Furthermore, the phasic contractile responses to noradrenaline in calcium-free medium (presumed to be due to mobilization of membrane bound calcium pool) were significantly (p < 0.05) attenuated by MPTP. The results suggest that MPTP relaxes rat aortic smooth muscle by a mechanism mediated, at least in part, by impairment of calcium influx through receptor-operated channels, as well as inhibition of calcium release from a membrane bound pool.

Inhibition of rat mitochondrial functions in vivo by 6-OHDA and reserpine.

Reserpine caused a decrease in the state 3, respiratory control ratio (RCR) and ADP/O ratio in frontal cortex, striatum and liver of rats 1 h after drug administration. State 4 respiratory rate was stimulated in frontal cortex and striatum. In the liver, 6-OHDA decreased the ADP/O ratio when both pyruvate/malate and succinate were used as substrates. Reserpine induced changes in the activities of Na+K(+)-ATPase and Mg(2+)-ATPase in frontal cortex and liver 15 min and 4 h after administration of the drug. In the liver only 6-OHDA caused the depression of Mg(2+)-ATPase activity (P < 0.05). Reserpine altered the levels of K+, Na+ and Ca2+ cations in rat frontal cortex and striatum, while 6-OHDA caused a decrease in the amount of Mg2+ in liver (P < 0.05).

Studies on schistosomiasis in the Niger Delta: Schistosoma intercalatum in the urban city of Port Harcourt, Nigeria.

Ova of S. intercalatum have been found in the urban city of Port Harcourt in the Niger Delta area of Nigeria, following examination of stool and urine samples from 1,709 persons (5-15 years of age) resident in various parts of the city. The ova occurred only in urine, with prevalence ranging from 1.0% to 9.8% with an overall prevalence of 5.7%. The intensity of the infection was low. Most infected individuals had counts of less than 500 ova in total bladder content. There was no significant difference in either the prevalence or intensity of the infection among the sexes (Male; prevalence 6.1%, intensity 527.3 vs Female; prevalence 5.4%, intensity 500.9). No case of infection with either S. haematobium or S. mansoni was encountered in the study. Malacological surveys in the gutters, creeks, streams and stagnant waterbodies within the city showed the presence of Lymnaea natalensis, Bulinus forskalii, Pila ovata, Melanoides tuberculata, Physa sp., Lanistes ovum and Segmentorbis sp. B. forskalii is indicated as the probable vector of S. intercalatum in the city. The growing problem of urban schistosomiasis in tropical Africa is discussed. Further studies on urban transmission and epidemiology of schistosomiasis in the Niger Delta area of Nigeria is also indicated.

Biochemical studies on the effects of continuous light on the albino rat retina.

The causal mechanism of light damage in the albino rat retina has been investigated. Male and female albino Wistar rats weighing 200-300 g and previously maintained in normal room lighting of approximately 15 hr light (0.85 +/- 0.05 X 10(-4) W cm-2) per 9 hr dark cycle were simultaneously exposed continuously to uniform fluorescent light flux of 3.01 +/- 0.5 X 10(-3) W cm-2 for a period of 6-18 hr. The animals were killed immediately after exposure and the retinas analysed for their contents of DNA, protein and lipids. There were significant losses of retinal DNA, protein, total lipid and polyunsaturated fatty acids, particularly docosahexaenoic acid. The losses were progressive with duration of exposure. There were also changes in phospholipid subclasses. These results could indicate altered photoreceptor-membrane viability secondary to continuous illumination. The ultimate effect would be the loss of photoreceptor cells with a concomitant loss of normal physiological function. Generally, gender was found to play no significant role, thus excluding possible endocrine interference. It is suggested that lipoperoxidative reactions could account for the observations made in this study. The danger of over-exposure to radiant flux in the tropics is inferred from these observations.

Fatty acid profiles in mental disease. Part 1. Linolenate variations in schizophrenia.

Lipids were isolated from 6 patients suffering from schizophrenia and also from 6 age-matched healthy controls. The extracted lipids were fractionated into erythrocyte and plasma lipids. Column and thin-layer chromatography on silica gel were employed further to isolate the extracts into sub-classes within the major neutral and polar lipid classifications. The fatty acid composition of each sub-class was then monitored by gas chromatography after transmethylation. A significantly higher proportion of linolenic acid (18:3w3) was found in schizophrenics when compared with the controls. The change was reflected in both the neutral lipids and phospholipids from plasma and erythrocytes of the patients. On average, 8.7 +/- 2.6 and 3.9 +/- 1.5 mole % linolenate/100 mg lipid extract were obtained from the plasma of patients and healthy controls, respectively, while 8.6 +/- 2.3 and 3.0 +/- 1.2 mole/% linolenate/100 mg lipid were recorded from the red blood cells. The other fatty acids investigated did not show such significant differences between patient and healthy subject. A net increase in the amount of total fatty acid was recorded in the patients and it is thought that either linolenate alone or linolenate together with other polyunsaturated fatty acids not considered here are responsible for these observations. Correlations of these findings with the pathology of schizophrenia are discussed.