Arsenic induced toxicity on testicular tissue of mice.

Effect of arsenic was studied on the testicular tissue of Swiss albino mice. Sodium-meta-arsenite (NaAsO2) was administered to adult mice (25 +/- 30 g) at a dose level of 30 mg/L and 40 mg/L through drinking water for 30, 45 and 60 days. After the treatment, the testicular organ was removed, weighed and processed for histopathological observation. No change in the body weight was recorded in treated groups after arsenic exposure but significant decrease in the relative testicular weight was observed in comparison with the control. The result showed that arsenic-treated mice exhibited dose dependent gradual reductions in seminiferous tubular diameter and various gametogenic cell population i.e. resting spermatocyte, pachytene spermatocyte and step-7-spermatid except spermatogonia. Leydig cell atrophy was significantly increased in dose dependent manner indicating a definite effect of arsenic on the spermatogenesis in mice. These observations were supported by gradual reduction in Leydig cell population in the above treated groups. In conclusion, the above results confirm the toxic effect of arsenic in testis of mice.

Effect of gamma-irradiation on H3 histone and DNA in solution.

Three methods, namely, absorbance of colour by reaction with Folin-Ciocalteau reagent, UV absorbance and fluorescence intensity measurements for detection of H3 histone in 0.15 M standard saline citrate (SSC) solution were compared. Maximum sensitivity was found with the Folin-Ciocalteau method. Effect of varying pH and of gamma- radiation on H3 histone and on interaction of H3 histone with DNA were studied. For this, solutions of H3 histone in SSC, in 0.9% NaCl, H3 histone + DNA in 0.9% NaCl were subjected to varying pH (1-10) and gamma- radiation (dose 10-50 Gy) and lambda(max) and Alambda(max) were monitored. From the molar ratios of histone and DNA in the complex, it was observed that at gamma -radiation dose of 50 Gy and pH 8.54, there was a depletion of 6-8 microg/ml of histone from the histone-DNA complex.

Comparative effects of prenatal and postnatal undernutrition on learning and memory in rats.

Effects of pre- and post-natal undernutrition on learning and memory parameters were studied in albino rats. Prenatal undernutrition was induced in rat pups by restricting the mother's diet by 50% during the entire gestation period, whereas postnatal undernutrition was induced in rat pups by restriction of their diet by rotating them between lactating and non-lactating maternalised females for 12 hr each day during suckling period from 2nd day to 18th day after birth. At 2.5 to 3 months of age all the rat offsprings were subjected to (i) original and reversal discrimination learning, (ii) passive avoidance, and (iii) active avoidance and its retention tests. The results indicate that both pre- and post-natal undernutrition in rat pups caused significant deficits in original and reversal discrimination learning, retention of passive avoidance after one week retention interval, and retention of active of avoidance learning. However, both pre- and post-natal undernutrition did not show significant effect on acquisition of active avoidance and retention of passive avoidance after 24 hr retention interval.

Behavioural effects of prenatal and postnatal undernutrition in rats.

Effects of pre- and post-natal undernutrition on anxiety and depression paradigms were studied in albino rats. Prenatal undernutrition was induced in rat pups by restricting the dam's daily food during the gestation period whereas postnatal undernutrition in rat pups was induced by rotating them between lactating and non-lactating maternalised females daily for 12 hr during suckling period from 2nd to 18th day after birth. At 2.5 to 3 months of age all the rat pups were subjected to (i) elevated plus maze behaviour, (ii) open-field behaviour, and (iii) swimming induced behavioural despair tests. The results indicate that postnatal undernutrition caused significantly increased anxiety in the elevated plus maze as well as in open-field behaviour tests. Whereas prenatal undernourishment caused lesser degree of anxiogenic behaviours in the elevated plus maze test. Prenatally undernourished rats showed increased anxiety in the open-field behaviour test. Both, pre- and post-natal undernutrition also lead to increased depressive behaviour in the behavioural despair test and postnatal undernourishment caused greater degree of behavioural despair.

Radioprotective efficacy of HT + AET in encapsulated form.

Entrapment of 5-hydroxyl-L-tryptophan (HT) in erythrocyte ghost prepared by hypotonic method and high voltage electric discharge method are nearly same. Release of HT with beta-aminoethylisothiuronium bromide hydrobromide (HT + AET) in in vitro system is rapid but only a portion of the entrapped amount is released. Release of HT + AET in serum marginally increases at 2 hr. Compared to release in in vitro medium the release in serum is less. Survival studies with Swiss albino mice indicates that compared to HT alone, the combination of HT + AET shows about 9 times percentage survival. The same combination in the encapsulated form show comparable percentage survival though the amount needed is 1/200th times compared to free form.

Safety of intrauterine administration of purified neem seed oil (Praneem Vilci) in women & effect of its co-administration with the heterospecies dimer birth control vaccine on antibody response to human chorionic gonadotropin.

Praneem Vilci (PV), purified neem oil was reported to exercise a reversible antifertility effect after a single intrauterine instillation in rodents and primates without any adverse effects. After toxicology, drug regulatory and ethical clearances, a phase I clinical trial was conducted on PV. Eighteen healthy tubectomised women were enrolled to evaluate the safety of a single intrauterine instillation of PV and to determine the effect of its co-administration on anti-hCG response to the heterospecies dimer (HSD) hCG vaccine. Eight women received PV alone and ten women were given the HSD-hCG vaccine in addition. Base-line and post-treatment haematological and biochemical profiles were determined as also the mid-luteal serum progesterone. Endometrial biopsies were examined to assess ovulatory status and the effect of intrauterine treatment with PV on the endometrium. Anti-hCG antibody titres were estimated in women who were concurrently immunized with the HSD vaccine. No untoward reaction was observed in any woman. Menstrual pattern and ovulatory status remained unaltered. Endometrial biopsy after PV instillation in one woman showed non-specific endometritis but she remained asymptomatic. Mild eosinophilia was seen in two women and this reverted to normal on its own. All women receiving PV and the HSD vaccine generated antibodies against hCG. Our data show that intrauterine administration of PV is safe and does not prevent the antibody response to HSD-hCG vaccine.

Anxiolytic activity of piracetam, a nootropic agent, following subchronic administration in rodents.

Piracetam (PIR), a cyclic GABA derivative without GABA-mimetic activity, is classified as a nootropic agent, a new class of psychotropic drugs which augment learning acquisition and retention of memory. The present study indicates that PIR has significant anxiolytic activity in rodents following subchronic, but not acute administration, when tested against several paradigms of experimental anxiety. Thus, PIR (250 and 500 mg/kg), administered orally for 7 and 14 days, exhibited anxiolytic activity in the open-field, elevated plus-maze and footshock-induced fighting in paired mice paradigms, as well as in the Vogel's conflict test in rats. In addition, PIR induced significant reduction in rat brain tribulin levels, a putative endocoid marker for anxiety, produced by pentylenetetrazole, an anxiogenic agent. On the contrary, single acute administration of PIR failed to induce any anxiolytic effect. The present study, thus, confirms clinical reports that PIR can induce a delayed antianxiety effect in psychogeriatric individuals and in chronic alcoholism.

Latency of memory consolidation induced in mice by piracetam, a nootropic agent.

Piracetam (PIR), a cyclic GABA derivative, is the prototype of a new class of psychoactive drugs, the nootropic agents, which improve learning acquisition and the retention of the learning as memory. It was proposed that nootropics act on processes essentially involved in information storage, thus facilitating memory. This property can best be investigated by drug administration after the learning trial and assessing subsequent retention performance. The present study was designed to evaluate the effective time period of memory consolidation, induced by piracetam, by assessing the retention of a learned task in two behavioural paradigms, following administration of the drug after learning acquisition. Physostigmine was used as the standard drug because of its well established facilitation of memory storage. PIR (250 and 500 mg/kg, ip) and physostigmine (0.05 mg/kg, ip) were administered in different groups of mice 5 min, 1, 2, 4, 8, 12 and 24 hr after learning acquistion of two passive avoidance tasks and the retention performance was evaluated 3 days later. The results indicate that, while physostigmine induced significant memory consolidation when administered up to 2 hr after learning acquisition, PIR induced retention of learning beyond this period. Thus, the highest effective post-trial interval for the lower and higher dose of the drug was 8 and 12 hr, respectively, in both the test paradigms. The results confirm that nootropics, like piracetam, are capable of memory consolidation, as assessed by retention of learning, even after intervals of 8 to 12 hr between learning and drug treatment.

Effect of piracetam on electroshock induced amnesia and decrease in brain acetylcholine in rats.

Piracetam, a prototype of a new class of psychotropic agents, the nootropic agents, which improve learning ability and memory retention, was found to induce a dose-related prevention of disruption of acquisition of a passive avoidance response produced by electroshock application. The amnesia attenuating effect of piracetam was accompanied by prevention of the decrease in acetylcholine concentrations of rat brain induced by electroshock. The study indicates that the cognition enhancing effect of piracetam may be due to a facilitatory effect on cholinergic transmission.

Effect of dihydroergotoxine, a cerebral vasodilator, on cognitive deficits induced by prenatal undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 Charles Foster strain albino rats, which were equally distributed into 8 evenly matched groups, following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and dihydroergotoxine (3 mg/kg, i.p.). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/dihydroergotoxine treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for passive avoidance learning. The results indicate that undernutrition caused significant original and reversal discrimination learning, deficits whereas environmental deprivation attenuated only the original discrimination learning performance. Dihydroergotoxine treatment facilitated the learning performance of rats in both the original and reversal learning tests. Nutritional, environmental and dihydroergotoxine treatments had no effect on the retention of the passive avoidance learning, both at 24 hr and 1 week intervals. Dihydroergotoxine treatment attenuated the learning deficits induced by prenatal undernutrition. The results indicate that dihydroergotoxine is not likely to be useful in cognitive deficits, induced by malnutrition, though it facilitated learning acquisition, since it had no effect on retention.

Effect of pyritinol, a cerebral protector, on learning and memory deficits induced by prenatal undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 CF strain albino rats, which were equally distributed into 8 evenly matched groups following a 2 x 2 x 2 factorial design, by varying three independent factors at two levels: nutrition--normal and undernutrition; environment--enrichment and impoverishment, and drug treatment--vehicle and pyritinol (100 mg/kg, ip). Prenatal undernutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/pyritinol treatments were given during the postweaning period of the pups. The rats were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. Thereafter, the animals were tested for the passive avoidance learning. The results indicate that undernutrition caused significant original discrimination learning deficits whereas environmental deprivation attenuated both the original and reversal learning performance. Environmental impoverishment attenuated the retention of passive avoidance behaviour but undernutrition had no effect on this paradigm. Pyritinol treatment improved the learning and retention performance of normally reared rats and also attenuated the original and reversal learning deficits induced by parental undernutrition and postweaning environmental impoverishment. The results indicate that pyritinol may be useful in learning and memory deficits induced by malnutrition and environmental deprivation.

Effect of piracetam, a nootropic agent, on discrimination learning deficits induced by parental undernutrition and environmental impoverishment in young rats.

The study was conducted on 64 Charles Foster albino rats which were equally distributed into 8 even-matched groups, following a 2 x 2 x 2 factorial design by varying three independent factors at two levels: nutrition--normal and undernutrition, environmental--enrichment and impoverishment, and drug treatment--vehicle and piracetam (100 mg/kg, ip). Prenatal nutrition was induced by restricting the mother's food intake. The environmental enrichment/impoverishment and the vehicle/drug treatments were given during the postweaning period of the rat pups. The animals were subjected to original and subsequent reversal brightness discrimination learning tests in a single unit T-maze at 8-9 weeks of age. The results indicate that undernutrition and environmental impoverishment significantly attenuated the original discrimination as well as the reversal discrimination learning. Piracetam treatment improved the learning performance of normally reared rats and also attenuated the original and reversal learning deficits induced by prenatal undernutrition and postnatal impoverishment. The results indicate that piracetam may be useful in memory deficits induced by malnutrition.

Effect of piracetam, a nootropic agent, on rat brain monoamines and prostaglandins.

Piracetam is the prototype of a new class of psychotropic drugs, the nootropic agents, which are claimed to selectively improve the higher telencephalic integrative activities. The effect of piracetam on rat brain monoamines and prostaglandins (PGs) was assessed so as to garner information on its mode of action. Two doses of the drug were used, a lower dose (20 mg/kg ip) and a higher dose (100 mg/kg, ip), the latter being known to exert a facilitatory effect on learning and memory. Piracetam produced a dose-related effect on rat brain serotonin (5HT) and noradrenaline (NA), with the lower dose inducing a decrease in 5HT levels and an increase in NA concentrations. The higher dose of piracetam produced the opposite effect. Dopamine (DA) levels were not significantly affected. The lower dose of the drug attenuated 5HT turnover and augmented that of NA, whereas the higher dose of piracetam produced the reverse effects, in clorgyline treated rats. The lower dose of piracetam produced a slight and statistically insignificant increase in rat brain PGE2 and PGF2 alpha. However, the higher dose of the drug produced marked increase in the levels of both the PGs. The observed biochemical effects may provide a basis for the nootropic effect of piracetam. However, they may also be due to the GA-BA-mimetic action of the drug, particularly those observed with the lower dose of piracetam.