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The oral use of chewing tobacco has greatly increased in recent years, and this usage is associated with cancers of the mouth, lip, nasal cavities, esophagus and gut. Use of chewing tobacco is extremely popular in Far East and Middle East countries. In some of these countries, these chewing tobaccos are mixed with areca nut, lime and catechu and sold as pan masala. In this study, we examined three different forms of commercially available pan masala, and examined the development of cytotoxicity using primary culture of normal human oral keratinocytes (NHOKs). NHOK cells were treated with three different forms of pan masala, gutkha, pan masala with saccharin and pan masala as well as Kentucky smokeless chewing tobacco (STE) and the development of oxidative stress, and DNA damage were monitored. The results of our study demonstrated significant amount of the superoxide anion production, lipid peroxidation, DNA fragmentation and DNA ladders with all of the chewing tobacco materials tested. Laser scanning microscopy revealed concentration-dependent effects of STE on the modulation of intracellular redox states. The results, thus, document that the cytotoxic effects of the chewing tobaccos including pan masalas are mediated through the production of the reactive oxygen species.

Experiments were designed to examine if Actinomycin D, an antibiotic, and Amica 30, a homeopathic drug used against shock and injury, can ameliorate cytogenetic damage induced by single or multiple exposures to ultrasonication. Separate sets of healthy mice were directly exposed to sonication for two minutes either once or they received multiple exposures at an interval of 20 days. The mice were then assessed at different intervals, against suitable controls, using parameters like chromosome aberrations (CA), mitotic index (MI), sperm head anomaly (SHA) and micronucleated erythrocytes (MNE). Separate groups of sonicated mice were either orally administered with Arnica 30 (alcohol 30 in control) or injected intramuscularly with Actinomycin-D (AMD). Elevated frequencies of CA, MI, MNE and SHA were noted in sonicated series. AMD had genotoxic effects of its own and also had additive effects on sonication induced genotoxicity. Sonicated mice fed with Arnica 30 showed appreciably reduced genotoxicity as against alcohol 30 and distilled water fed controls, thereby showing ameliorating effect which may have human application.

The symbolic sequences of the exons that make human proteins are subjected to methods of statistical linguistics. The ideas developed for the natural languages by G. K. Zipf, when applied to these sequences, show significant promise. In particular, we argue, the Zipf's exponent differentiates, and hence, identifies disparate human sequences.

C-, G- and NOR bands have been studied in the female sex of Rhinomugil corsula. (Mugilidae, Pisces) by deploying the conventional methodologies with suitable modifications of minor nature. The diploid metaphase complements contained 48 acrocentric chromosomes. The localization of C-band heterochromatin was found to be mostly at or near the centromeric regions of the acrocentric chromosomes. The G-type bands were not so well defined, but some of the G-banded chromosomes also contained C-bands. Interestingly, silver-positive NORs were found at the telomeric ends of five acrocentric chromosomes, including one homologous pair having NORs in both chromatids, while one chromosome showed NORs in both of its chromatids and the other two had only one NOR localized at one of its chromatids. This would suggest that one homologue of the second pair of NOR-bearing chromosomes possibly underwent a chromatid exchange with a non-NOR bearing chromosome. This is quite a unique situation not reported earlier in any species of fish., though some other form of NOR-polymorphism/heteromorphism has rarely been reported. Therefore, further exploration in natural populations of this species to examine the other sex and to verify if there also exists other chromosomally polymorphic races (in respect of NOR-polymorphism) of this species, would be rewarding.

The authors attempted ureteral occlusion by means of heat application in nine ureters (24 sites) of New Zealand White rabbits with the electromagnetic field-focusing (EFF) device. The EFF device generates heat at the tip of a grounded probe by focusing eddy currents that have been induced within the tissues by an external radio-frequency field. The power settings were varied from 30 to 150 W. Heat was applied at multiple sites in each ureter. Immediate functional occlusion was seen in all nine ureters. Long-term complete occlusion was seen in six ureters at power settings ranging from 40 to 150 W, while long-term partial occlusion was seen in two ureters at 30-50 W. All sites at 30 W resulted in partial occlusions. Perforation of the ureter resulted in urinoma formation in one ureter at a site that was treated with 150 W. The EFF device can be used to endoluminally occlude the ureter by causing a fibrotic reaction to thermal injury. The effective power range for this application appears to be 40-100 W.

Samples of estuarine/sea fish and prawn purchased from different markets in and around Calcutta were analysed for mercury content in the edible portions by cold vapour AAS. The contents varied widely from 4.5 to 42.4 ppb. The internationally regulatory fixed levels for mercury in fish (of 1.0 and 0.5 ppm) appear to be too high in view of our findings and the acceptable weekly intake of mercury of 0.005 mg/kg body weight. It is suggested that the statutory permitted level of mercury in fish be reduced drastically from 500 to 50 ppb.

A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.

pH-Stat titration and ultraviolet absorption spectroscopy have been used to study the rates of ring-opening in a series of gamma-butyrolactones and their analogues. The half-lives for the lactones can be related to Hammett inductive and steric parameters.

The synthesis of 2-halo-1-adamantanemethanamines, 4-protoadamantanemethanamines, and 4-protoadamantaneamines is described. The anti-Parkinson activity of these amines in terms of reversal of reserpine-induced catalepsy in rats has been evaluated and compared with amantadine. 2-Bromo- and 2-chloro-1-adamantanemethanamines are shown to be twice as active as amantadine.

The synthesis of [1,2,3]triazolo[4,5-b][1,5]-, imidazolo[4,5-b][1,5]-, and pyrido[2,3-b][1,5]benzodiazepines is described. The antidopaminergic and anticholinergic activities of the compounds have been examined by the respective in vitro [3H]spiperone and [3H]QNB receptor binding assay. The neuroleptic potential has been further evaluated in terms of their ability to produce hypothermia and catalepsy in mice and a conditioned avoidance response in rats. Only compounds from the triazolobenzodiazepine series show antipsychotic potential. The lack of activity in the imidazolo- and pyridobenzodiazepine series indicates that the basicity of the heteroarene moiety may be determinant for activity.

The synthesis and pharmacological evaluation of a series of pyrazolo[b][1,5]benzodiazepines are described. Some of the 4-piperazinyl-2,10-dihydropyrazolo[3,4-b][1,5]benzodiazepine derivatives demonstrated potent anxiolytic activity in the three-part operant anticonflict test in rats. Compounds 21 and 30 were more active than the clinically effective anxiolytic chlordiazepoxide in releasing conflict-suppressed behavior. This study shows a dissociation of the anxiolytic and antidopaminergic activities found in the thieno- and dibenzodiazepine derivatives flumezapine and clozapine, respectively. Examples of the three other dihydropyrazolo[b][1,5]benzodiazepine ring systems are described and evaluated for comparison and were found to be less active.

The levels of antidopaminergic and anticholinergic activities of neuroleptics, 4-piperazinyl-10H-thienobenzodiazepines, are modulated by imposing steric impedence to the piperazine ring. The optimum situation in favor of the anticholinergic action is reached in compound 5, 2,3-dimethyl-7-fluoro-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine, where a maximum activity (equivalent to hyoscine), as measured by the [3H]QNB receptor binding assay, is obtained. The structure-activity relationships found highlight the importance of certain spatial dispositions of the distal piperazine nitrogen (electron lone pair) with respect to the tricyclic system. The evidence for molecular topography of these compounds is presented from X-ray, NMR, and other physical data. The conformational aspects for correspondence to the relevant receptors are discussed.

The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.

A series of 5-acyl-3-substituted-benzofuran-2(3H)-ones and their respective ring-opened o-hydroxy acids were synthesized. The antiinflammatory activity was evaluated in terms of their ability to improve adjuvant induced arthritis in rats. Their effect on the production of both cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acid in guinea pig peritoneal polymorphonuclear neutrophils (PMNs) was also examined. No correlation between the antiinflammatory activity and increasing stability of the lactones could be found. The degree of activity in general shown by the benzofuranones was similar to that of their corresponding o-hydroxy acids. This, coupled with the evidence from studies on opening of the lactone ring, suggests an in vivo transformation of the former into the latter. Benzofuranones displayed a dual inhibition of CO and LO products, while a moderate reduction in CO metabolites was shown by their acids.