ASSESSMENT OF RADON IN SOIL AND WATER IN DIFFERENT REGIONS OF KOLHAPUR DISTRICT, MAHARASHTRA, INDIA.

Researchers have already established that inhalation of high radon concentration is hazardous to human health. Radon concentration has been measured in water and soil, in various part of Kolhapur district has been carried out by the AQTEK Smart RnDuo which is an active device technique. The observed minimum value of the radon mass exhalation rate of the soil is 13.16 ± 0.83 mBq/kg/h and maximum is 35.11 ± 1.84 mBq/kg/h. The minimum value of the Radon concentration in water is 0.33 ± 0.052 Bq/L and maximum is 7.32 ± 0.078 Bq/L. These values of radon concentration are below the action of recommended level by the USEPA, which is set as the maximum contaminant level of 11.1-148 Bq/L of radon in drinking water. Total annual effective dose rate of water is 11 µSv/y. The purpose of present study is to assess radiological risk from consumption of water that provide in Kolhapur district and to evaluate the radon mass exhalation rate of soil in few places of Kolhapur district.

Seroquel, clozapine and chlorpromazine restore sensorimotor gating in ketamine-treated rats.

Sensorimotor gating of the startle reflex measured by prepulse inhibition (PPI) is impaired in schizophrenia patients and in rats treated with either dopamine (DA) agonists or with N-methyl-D-aspartate (NMDA) antagonists. While both typical and atypical antipsychotics restore PPI in DA agonist-treated rats, studies thus far have demonstrated that only atypical antipsychotics restore PPI in rats treated with NMDA antagonists. This model for predicting atypical antipsychotic properties has been studied extensively in rats, and there is interest in moving these studies into humans, where the NMDA antagonist ketamine is also reported to significantly reduce PPI. In anticipation of such studies, and to facilitate the use of this model in humans, we examined the effects of high and low potency typical antipsychotics (haloperidol and chlorpromazine), the atypical antipsychotic clozapine, and the putative atypical antipsychotic, Seroquel, on ketamine-disrupted PPI in rats, across a range of ketamine that produced submaximal, as well as maximal disruptions of PPI. Ketamine dose-dependently reduced PPI, and this effect was significantly opposed by Seroquel, clozapine and chlorpromazine, but not haloperidol. The effects of chlorpromazine on ketamine-disrupted PPI demonstrate that the ability of antipsychotics to restore PPI in NMDA antagonist-treated rats is not specific to clinically atypical antipsychotics. Receptor properties shared by Seroquel, clozapine and chlorpromazine, but not haloperidol, may implicate critical substrates in the NMDA antagonist-induced disruption of PPI.

Repeated testing of prepulse inhibition and habituation of the startle reflex: a study in healthy human controls.

The aim of this study was to examine the effect of repeated testing on prepulse inhibition (PPI) and habituation of the startle reflex. Fifteen healthy control subjects (eight males, mean age 30 years; seven females, mean age 29 years) were tested on three occasions across the same day separated by a minimum of 2 h. An acoustic probe of 40-msec bursts of 116 dB(A) white noise over a continuous background noise of 70 dB(A) was presented binaurally through headphones and the eye-blink component of the startle response was measured taking electromyographic recordings from the right orbicularis oculi. The test session was identical at each time point and consisted of two blocks of 12 randomly mixed trials of four pulse-alone, four 60-msec prepulse and four 120-msec prepulse trials enclosed by two blocks each of six pulse-alone trials. There was huge variation in individual response magnitude that was independent of subsequent PPI in both women and men. Women showed greater PPI in the second half of sessions with the 120-msec prepulse only; but PPI was not altered significantly in either group between sessions across the day. In general, there was good test-retest reliability of PPI especially within trial type. Normal reflex habituation occurred across sessions and this effect was preserved in sessions across the day. Latency of response was significantly reduced in a session by the 60-msec trial type compared to the 120-msec trial type, as previously reported. Our results suggest that measures of PPI and habituation of the startle response are appropriate and reliable for a within-subject, test-retest design.

Evidence for an inhibitory 5-HT4 receptor in urinary bladder of rhesus and Cynomolgus monkeys.

1. The present study shows that 5-hydroxytryptamine (5-HT) inhibits electrically-evoked contractions of isolated urinary bladder strips from Rhesus and Cynomolgus monkeys via activation of 5-HT4 receptors. 2. 5-HT (0.1 nM-10 microM) produced concentration-dependent inhibition of the contractile response to electrical stimulation yielding a pEC50 of 7.8 (Rhesus monkey) and 7.6 (Cynomolgus monkey). This action of 5-HT was mimicked by 5-methoxytryptamine, renzapride and BIMU 8, each of which behaved as a full agonist relative to 5-HT. However, the potency estimate for BIMU 8 (pEC50 = 6.5) in Cynomolgus monkey was low, relative to 5-HT, indicating a possible heterogeneity of 5-HT4 receptors. 3. The inhibitory action of 5-HT was resistant to antagonism by methysergide (1 microM) and ondansetron (5 microM), thereby eliminating a role for 5-HT1, 5-HT2 and 5-HT3 receptors. The 5-HT4 receptor antagonists, GR 113808 (10 nM), DAU 6285 (1-10 microM) and RS 23597-190 (1 microM), produced parallel, dextral displacements of the concentration-effect curves to 5-HT and other related agonists with affinity estimates in agreement with those defined previously in other 5-HT4 receptor assay systems. 4. Experiments using direct electrical stimulation of bladder smooth muscle indicate that the 5-HT4 receptors are located post-junctionally. 5. The inhibitory action of 5-HT in isolated urinary bladder of monkey differs from the excitatory effect of 5-HT in urinary bladder of man. Species variation and its implications for the development of therapeutic agents are discussed.

Pharmacological analyses of endo-6-methoxy-8-methyl-8-azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-2-oxo-1 H- benzimidazole-1-carboxylate hydrochloride (DAU 6285) at the 5-hydroxytryptamine4 receptor in the tunica muscularis mucosae of rat esophagus and ileum of guinea pig: role of endogenous 5-hydroxytryptamine.

Functional estimates of affinity for endo-6-methoxy-8-methyl-8- azabicyclo[3.2.1]oct-3-yl-2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxyla te hydrochloride (DAU 6285) were made at the 5-hydroxytryptamine4 (5-HT4) receptor in isolated preparations of rat esophageal tunica muscularis mucosae (TMM) and guinea pig ileum. In the TMM, relaxation of carbachol-induced contracture by 5-HT4 receptor agonism of longitudinal muscle was recorded. Estimated pA2 values for DAU 6285 of 6.9 to 7.2 were tissue, time (1-3 hr equilibration) and agonist-independent. However, DAU 6285 increased the maximal response to 5-HT and 5-methoxytryptamine in the TMM and augmented the contractile tone to carbachol. These effects were not observed in guinea pig ileum, suggesting a tissue-dependent mechanism. [3a-Tropanyl]-1H-indole-3-carboxylic acid ester (tropisetron) and 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557), two other 5-HT4 receptor antagonists, mimicked the effects of DAU 6285. Mechanistic experiments suggest agonism by endogenous 5-HT, within the isolated TMM, to explain the effects of 5-HT4 receptor antagonists. Pretreatment of rats with parachlorophenylalanine to deplete endogenous 5-HT, prevented the effect of DAU 6285 on the maximal response to 5-HT and carbachol-induced tone. In conclusion, DAU 6285 acts as a silent, competitive antagonist at 5-HT4 receptors in rat TMM and guinea pig ileum. However, in the TMM, endogenously released 5-HT confounds interpretation. The TMM, as a quantitative assay system for 5-HT4 receptor agonists and antagonists may be improved by pretreating rats with parachlorophenylalanine.