Genotoxicity in agricultural farmers from Guntur district of South India--A case study.

BACKGROUND: Pesticides play an important role in controlling the pests on agricultural crops and thereby to increase the yield of agricultural produce. Farmers occupationally exposed to pesticides during spraying activities are more prone to genotoxicity than unexposed. AIM: To assess the genotoxicity in farmers, engaged in spraying complex mixture of pesticides in the cultivation of cotton crops. MATERIAL AND METHODS: A total number of 152 male subjects were selected randomly from Guntur district of Andhra Pradesh (AP), South India. The demographic particulars viz., personal habits, duration of exposure to pesticides, types of pesticides used were collected from the study subjects using an interview schedule. Among them 76 subjects were farmers and the remaining individuals served as unexposed or controls. Blood samples from these subjects were collected for assessing the genetic damage by chromosomal aberrations (CAs) test and micronucleus test (MNT). RESULTS: The results of the study indicated that CA was significantly higher with 2.8% in farmers who were exposed to pesticides when compared to unexposed (0.72%). However, there was a minor difference in MN with 0.13% and 0.12% between exposed and unexposed which was not statistically significant (p < 0.05). CONCLUSION: A correlation between CA frequency and exposure to benzene hexachloride (BHC) pesticide residue was observed.

Evidence of mechanically activated processes in slow granular flows.

We study how a shear band in a granular medium dramatically changes the mechanical behavior of the material further in the non sheared region. To this end, we carry out a microrheology experiment, where a constant force F is applied to a small rod immersed outside the shear band. In the absence of a shear band, a critical force F(c) is necessary to move the intruder. When a shear band exists, the intruder moves even for a force F less than the critical force F(c). We systematically study how the creep velocity V(creep) of the rod varies with F(c) - F and with the distance to the shear band, and show that the behavior can be described by an Eyring-like activated process.

Long-term results of radiation therapy for juvenile nasopharyngeal angiofibroma.

PURPOSE: To analyze 15 patients treated with radiation therapy for juvenile nasopharyngeal angiofibroma (JNA) between June 1975 and March 1996. MATERIALS AND METHODS: All patients had a 2.5-year minimum follow-up. All patients had advanced disease (Chandler stage III or stage IV); two thirds of the patients had intracranial extension. RESULTS: Local control after radiotherapy was obtained in 13 of 15 patients (85%). Two patients had local recurrences, and both were salvaged with surgery for an ultimate local control rate of 100%. Late complications included cataracts in 3 patients, delayed transient central nervous system (CNS) syndrome in 1 patient, and a basal cell carcinoma of the skin in 1 patient. Of 15 patients, 13 (85%) had a complete response (CR) on physical examination following radiation therapy. The median time to CR was 13 months (range, 1 to 39 months). Of 6 patients with residual disease in more than 24 months, 2 (33%) had a recurrence, whereas no patient achieving CR in less than 24 months experienced a recurrence. CONCLUSIONS: Radiotherapy is an effective treatment for advanced JNA. Tumor regression usually occurs slowly over several months. JNAs that are slow to regress (greater than 2 years) may have an increased risk of recurrence.

The role of radiotherapy and limb-conserving surgery in the management of soft-tissue sarcomas in adults.

The treatment of soft-tissue sarcomas has undergone significant changes over the past several decades. Previously, patients were often treated with surgery alone, which frequently necessitated amputation of the affected extremity. Less extensive, limb-sparing operations combined with adjuvant irradiation are now feasible for most patients without compromising the likelihood of cure.

Novel antidiabetic and hypolipidemic agents. 5. Hydroxyl versus benzyloxy containing chroman derivatives.

Several thiazolidinediones having chroman moieties were synthesized and evaluated for their euglycemic and hypolipidemic activities. Some of the analogues having an aminoalkyl group as a linker between the chroman ring and 4-[5-(2,4-dioxo-1, 3-thiazolidinyl)methyl]phenoxy moiety seem to be better than troglitazone. In vitro transactivation assays of PPARgamma have been carried out with these glitazones to understand their molecular mechanism. For the first time we have found that some of the unsaturated thiazolidinediones are superior to their saturated counterpart in the in vivo assay. A more potent thiazolidinedione analogue than troglitazone is reported. Pharmacokinetic studies have shown that protection of the OH group in the chroman moiety leads to a decrease in metabolism, thereby resulting in a superior pharmacological profile.

Novel antidiabetic and hypolipidemic agents. 3. Benzofuran-containing thiazolidinediones.

Several thiazolidinedione derivatives having 5-hydroxy-2,3-dihydro-2, 2,4,6,7-pentamethylbenzofuran moieties and their 5-benzyloxy derivatives and 5-hydroxy-2,4,6,7-tetramethylbenzofuran moieties were synthesized and evaluated in db/db mice. Insertion of an N-Me group into the linker between thiazolidinedione and substituted benzofuran pharmacophores showed considerable improvement in their euglycemic activity. Further improvement has been observed when a pyrrolidine moiety is introduced in the structure to give 5-[4-[N-[3(R/S)-5-benzyloxy-2,3-dihydro-2,2,4,6, 7-pentamethylbenzofuran-3-ylmethyl]-(2S)-pyrrolidin-2- ylmethoxy]pheny lene]thiazolidine-2,4-dione (21a). At a 100 mg/kg/day dose of the maleate salt, compound 21a reduced the plasma glucose and triglyceride to the level of lean littermate, i.e. 8 +/- 1 mM, and is the most potent and efficacious compound reported in this series.

Novel euglycemic and hypolipidemic agents: Part-2. Antioxidant moiety as structural motif.

Several thiazolidinediones having antioxidant moities in their structural motif have been synthesised and evaluated for their euglycemic and hypolipidemic activities. A few of them have been found to be superior to troglitazone.

Congenital double lip: a review of seven cases.

Congenital double-lip deformity is an infrequent developmental abnormality affecting the lips, more commonly the upper lip. We report seven cases of double lip, all in males, of which six were in the upper lip and one in the lower lip. It was quite interesting to observe that in the upper lip, the buccal portion of the double lip appeared on either side with a midline constriction; in the lower lip, it was prominent in the midline without any central constriction. Surgical excision under regional nerve block anesthesia gives good results. The embryology, clinical appearances, and histopathology are discussed with a review of the literature.

Triple nostrils: a case report and review.

In this paper we present a case of a "third nostril" situated below the left nostril and passing posteriorly into the nasal cavity. In all previously published cases the supernumerary nostril has been situated superior to the normal nostrils.

Effect of butylated hydroxytoluene and other antioxidants on mouse lung metabolism.

Toxic doses of butylated hydroxytoluene (BHT), a phenolic antioxidant commonly used as a food additive, are known to produce lung damage. In this study, 3 days after a single ip injection of 62.5, 215, or 500 mg/kg BHT in mice there was a dose-dependent increase in lung weight. This concentration dependence with injected BHT was accompanied by increases in lung DNA and nonprotein sulfhydryl levels and in whole lung tissue enzyme activities of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and superoxide dismutase. The increased enzyme activities are considered to correspond to inflammatory and proliferative pulmonary changes resulting from acute lung cell injury and necrosis, which have been described previously, and cannot be construed as evidence for a primary oxidant-induced pulmonary lesion. The mechanism of BHT-induced lung changes may not be related to the antioxidant property of BHT, since vitamin E, n-propyl gallate, ethoxyquin, N,N'-p-phenylenediamine, and the structurally similar compound, butylated hydroxyanisole did not appear to produce the gross anatomical or biochemical lung changes observed with BHT.

Effect of pretreatment with antiinflammatory agents on paraquat toxicity in the rat.

Aspirin (ASA), indomethacin (IND), hydrocortisone (HYC) or 0.25% agar (control) were administered (p.o.) daily to rats for 5 days. Following drug pretreatments, the activities of cytosolic superoxide dismutase (SOD), glutathione peroxidase (GP) and glutathione reductase (GR) were elevated 30-70%, 5-25% and 8-25%, respectively. In a second experiment, rats pretreated as above were injected (ip) on the 5th day with paraquat (PQ) (29 mg/kg). Rats in each group expired more ethane 2 hours after PQ injection. After 22 hours, expired ethane returned to zero time levels. All control rats died within 48 hours after PQ injection. At the end of 48 hours, rats pretreated with ASA, IND, or HYC demonstrated survival rates of 13%, 31%, and 47%, respectively. PQ injection produces marked elevations of SOD (82%), GP (328%), and GR (36%) in the lungs of PQ-injected controls rats over non-PQ injected controls. Elevation of these enzymes were also noted in drug-treated rats after PQ injection but at values less than PQ-injected controls. Anti-inflammatory drugs were tested in rat liver homogenates for their ability to inhibit thiobarbituric acid (TBA) reactive product formation. Only the addition of HYC resulted in a decrease formation of TBA-reactive products. Thus in vitro studies suggest that the antiinflammatory drugs tested, other than HYC, may have other mechanisms of actions in addition to inhibition of lipid peroxides.

Enhanced lung toxicity of O2 in selenium-deficient rats.

To test the hypothesis that glutathione (GSH) peroxidase is an important component of the lung's anti-oxidant defense systemes, O2 toxicity was studied in selenium (Se)-deficient rats. Chronic respiratory disease free rats fed a Se-deficient diet or a diet supplemented with Se for 40 days after weaning were exposed to 80% O2 at atmospheric pressures for 3 days. Activities of GSH peroxidase in lungs of Se-deficient rats were markedly lower than corresponding activities in rats supplemented with 0.5 or 2.0 ppm Se. With O2 exposure, 35% of the rats fed the Se-deficient regimen died, whereas all rats fed Se-supplemented diets survived. Lungs from surviving Se-deficient rats exposed to O2 were edematous. The data suggest that the toxic effects of O2 are enhanced in Se-deficient rats and that nutritional factors contribute to lung susceptibility to oxidant-induced damage.