Testosterone and postnatal ontogenesis of hypothalamic mu ([3H]dihydromorphine) opioid receptors in the rat.

Brain opioids modulate the activity of the hypothalamo-pituitary complex by binding to specific receptors which have been subdivided at least into 3 subclasses (mu, kappa, delta, etc). mu-Receptors and their ligands seem to be particularly involved in the control of gonadotropin and prolactin release. It is known that the neuroendocrine system, as well as the brain opioid systems and their receptors, are not fully mature at birth; it is also known that the postnatal maturation of many brain machineries is under the control of androgens secreted by the developing testes. Consequently, it has been investigated whether the presence or the absence of testosterone at time of birth may induce changes of the binding characteristics of hypothalamic mu-opioid receptors. The experiments have been performed by evaluating the maximal binding capacity (Bmax, an index of the number of receptors), and the affinity constant (Ka) of the specific mu-ligand dihydromorphine in hypothalamic plasma membrane preparations derived from normal male rats, normal female rats, male rats orchidectomized 2 days after birth and female rats treated 2 days after birth with 1.25 mg of testosterone propionate. Animals belonging to the 4 groups were killed at days 16, 26 and 60 of age. The results obtained show that, at 16 days of age, in the 4 groups of rats the number of hypothalamic mu receptors is identical. At 26 days a significant increase in the number of mu-receptors occurs in normal female animals, while their levels remain similar to those found at 16 days in the other 3 groups of animals. At 60 days of age, the number of mu-receptors in normal females remains elevated, while the number of mu-receptors increases to reach normal female levels in the hypothalamus of neonatally castrated males. At 60 days, there were no changes in normal males or in androgenized females. The variations here reported took place without any change of the Ka of dihydromorphine for the mu-receptors. These data show a sexual dimorphism of hypothalamic mu-receptors and suggest that their ontogenetic development may be linked to the presence or the absence of androgens at time of birth.     

Tetrahydroaminoacridine improves passive avoidance retention defects induced by aging and medial septal lesion but not by fimbria-fornix lesion.

The present study examines whether tetrahydroaminoacridine (THA) can improve the deterioration in passive avoidance (PA) retention performance induced by medial septal (MS) and fimbria-fornix (FF) lesions in young rats or by aging. Retention of young MS-lesioned rats was improved by pretraining injection of THA at 3 mg/kg, but not by THA at 1 mg/kg or by either of the posttraining doses of THA (1 and 3 mg/kg). Pretraining injections of THA at 1 or 3 mg/kg had no effect on the PA retention performance of FF-lesioned rats. Age-induced PA failure was alleviated by pretraining administration of THA at 1 and 3 mg/kg. Posttraining injections of THA (1 or 3 mg/kg) had no effect on PA retention performance of aged rats. These results demonstrate that 1) THA may improve hippocampal cholinergic denervation-induced functional deficits and 2) some of the age-related PA deficits may be due to a cholinergic deficit and can be reversed with THA.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opsoclonus in organophosphate poisoning

Transient opsoclonus was observed in a patient who attempted suicide with the organophosphate insecticide Malathion (diethyl[dimethoxyphosphinothioyl]thiobutanedioate). Several toxins can cause opsoclonus, and these must be considered in its differential diagnosis. Eye movement disorders are one of the more common manifestations of organophosphate intoxication, and opsoclonus should now be included among these. Acetylcholine may be a neurotransmitter in the ocular motor pathway.     

Linkage mapping of a mouse gene, iv, that controls left-right asymmetry of the heart and viscera.

Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50% exhibit normal situs. The affected gene product has not been identified in these animals. To study the normal function of iv, we have taken an approach directed to the gene itself. As a first step, we have mapped iv genetically, by examining its segregation in backcrosses with respect to markers defined by restriction fragment length polymorphisms. The iv locus lies 3 centimorgans (cM) from the immunoglobulin heavy-chain constant-region gene complex (Igh-C) on chromosome 12. A multilocus map of the region suggests the gene order centromere-Aat (alpha 1-antitrypsin gene complex)-(11 cM)-iv-(3 cM)-Igh-C-(1 cM)-Igh-V (immunoglobulin heavy-chain variable-region gene complex).     

Bacteriological study of drinking water during epidemic of cholera in Delhi

Sixty drinking water samples collected from various sources in different areas of Delhi during epidemic of cholera and gastroenteritis were analysed for bacteriological standards. Only 27 (45 per cent) samples were found to be satisfactory for human consumption. Remaining thirty-three (55 per cent) samples showed presence of coliform organisms with MPN value ranging from 10 to 1800+ per 100 ml. Among these positive samples, 31 (93.9 per cent) samples contained faecal coli. Twenty out of thirty (66.6 per cent) Hand pump, 9 out of 21 (42.8 per cent) Taps 2 out of 4 (50 per cent) Tube well and 2 out of 5 (40 per cent) of miscellaneous sources showed contamination with coliform organisms.     

The pH Optima for Papain and Bromelain Treatment of Red Cells

The action of papain and bromelain, prepared over a pH range from 4.6 to 8.6, was evaluated for the ability to render red cells agglutinable by five incomplete antibodies of differing blood group specificities using a two-stage technique. The optimal pH for treatment of red cells by activated papain or bromelain was between 5.4 and 5.8. Above this pH range, a fall in serological sensitivity was apparent which was much more pronounced with papain than with bromelain. The optimal pH for enzyme treatment of red cells can be achieved in two-stage techniques, but not in one-stage techniques due to the buffering effect of serum proteins.     

Malaria resurgence in India: a critical study

In 1953, the Indian National Malaria Control Programme (NMCP) was started. Encouraged by the results, and the fact that insecticide resistance in vector species may evolve and become an obstacle, in 1958 a control programme was converted to the National Malaria Eradication Programme (NMEP). By 1964, malaria was eradicated from 88% of the area and it was in the advanced stage of spraying in the remaining parts. At that time, focal outbreaks that occurred in 1965 and increased in later years, could not be contained due to the shortages of DDT. As a result, large areas in consolidation and maintenance phases were reverted to the attack phase. Besides, the infrastructure in general health services was not adequate and mature enough to take up surveillance and vigilance. This produced a large number of secondary cases due to the re-introduction and relapse of malaria. Added to this was the problem of urban malaria, the control of which was the responsibility of local bodies. Malaria cases increased in towns, and started diffusing to the rural areas, due to inadequate staff and the shortages of malarial larvicidal oil (MLO). Later, it turned out, that while it was technically feasible to eradicate malaria from 91% of the population, the strategy of indoor spraying of DDT to interrupt transmission did not succeed in 9.0% of the population, despite more than 12-14 years of regular spraying. During the years of resurgence, there was no research support to the programme, so that technical problems were not properly appreciated, understood and tackled. The reservoir of parasites that were present throughout the country started multiplying and spreading to newer areas due to the presence of vectors in high densities. Thus malaria resurged and re-established itself even in areas that were at one time freed from the disease. The analysis of the pattern of malaria resurgence revealed that malaria outbreaks preceded the true problem of insecticide resistance. It is noteworthy to mention that malaria resurgence occurred in towns where the control measures were non-insecticidal and in regions which were not under the influence of insecticide-resistant vectors. The study also revealed that resurgence occurred before the introduction of high-yielding varieties programme in the country, and had no relationship to either the cotton or rice growing or intensive agriculture.