Influence of time and mode of exposure on biotransformation of naphthalene by Juvenile starry flounder (Platichthys stellatus) and rock sole (Lepidopsetta bilineata)

Juvenile starry flounder (Platichthys stellatus) and rock sole (Lepidopsetta bilineata) were force-fed 56 Ci each of 1-³H-naphthalene dissolved in salmon oil. Values for radioactivity associated with naphthalene and the metabolite fraction were determined for various tissues and body fluids. Results show that these pleuronectids extensively metabolize dietary naphthalene. The rates of decline in naphthalene concentrations (expressed as disintegrations per minute per milligram of dry tissue) were greater than the rates of decline in metabolite concentrations (dpm/mg) in liver, blood, and skin; therefore, relative proportion of metabolites to naphthalene increased with time and at 168 hr after the initiation of the naphthalene-exposure, more than half of the total radioactivity in both species of fish was associated with the metabolites.Profiles of metabolites in liver, skin, and bile were obtained using thin-layer chromatography. 1,2-Dihydro-1,2-dihydroxynaphthalene constituted 38.7 and 39.7%, respectively, of the total extracted metabolites in livers of the naphthalene-exposed rock sole and starry flounder at 24 hr, whereas the bile from both species contained primarily (>90%) conjugates. From 24 to 168 hr, a significant (P < 0.05) decrease in the proportion of the dihydrodiol derivative and a concomitant increase in the proportion of conjugates—specifically, sulfate/glucoside fraction-were observed with livers of both rock sole and starry flounder. No significant change occurred in the spectrum of biliary metabolites with time. The pattern of metabolites in skin of both species was qualitatively similar to that in liver; however, the proportion of the dihydrodiol was greater in skin than in liver at 24 hr.When naphthalene (56Ci) dissolved in salmon oil was administered to starry flounder via intraperitoneal injection, the extent of biotransformation was less than after dietary exposure. Moreover, metabolites in the livers of the fish in the injection study were predominantly (76.7% of total extracted metabolites) non-conjugates at 24 hr. Once again, from 24 to 168 hr, an increase in the proportion of the sulfate/glucoside fraction and a concomitant decrease in the proportion of the dihydrodiol was observed with liver.These studies demonstrate that the extent of biotransformation of naphthalene and the types of metabolites remaining in tissues (e.g., liver) of flatfish are greatly influenced by both the mode of exposure and the time elapsed after the exposure is initiated. It appears therefore, that different exposures (e.g., in water, food, or sediment) of pleuronectids to polycyclic aromatic hydrocarbons may result in different degrees of alteration in genetic material because of variability in accumulation of non-conjugated metabolites, some of which are implicated in covalent binding with DNA in terrestrial mammals.     

Chlorinated hydrocarbon insecticide residues in tennessee honey and beeswax

Several samples of commercial grade honey collected from different parts of Tennessee during the summer of 1973 were analyzed for chlorinated hydrocarbon insecticide (CHI) residues. A Modified Mill's Procedure was used to cleanup the samples prior to gas Chromatographic analysis using electron capture (EC) detection. The presence of CHI residues was confirmed by analysis on three different columns of widely varying polarity. Most of the samples contained CHI residues at 0.01—0.30 parts per billion (ppb) level. Beeswax produced during the same season contained several times higher levels of the residue than the honey samples. Recoveries of CHI residues varied from 81–95 percent by the procedure employed.     

Anticarcinogenic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a curcumin analog on DMH-induced colon cancer model.

1,2-Dimethylhydrazine (DMH) is a toxic environmental pollutant which was reported also to be a colon-specific carcinogen. This study was performed to study the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a bisdemethoxycurcumin analog (BDMC-A) on DMH-induced colon carcinogenesis in male Wistar rats and effects were compared with that of the reference drug, curcumin. Rats were given a weekly subcutaneous injection of DMH (20mg/kg body weight) in the groin, for 15 weeks. After a total experimental period of 32 weeks (including 2 weeks of acclimatization) tumor incidence was 100% in DMH-treated rats. Tumor was identified histologically as adenocarcinoma. Dysplasia, papillary pattern, cellular pleomorphism and carcinomatous glands were also noticed in DMH-treated rats. However, there was no colonic tumor in DMH+BDMC-A- and DMH+curcumin-treated rats but, lymphocyte infiltrations were observed. The levels of total bile acids and cholesterol in 24h fecal samples were significantly lower in DMH administered rats when compared to control rats, while, the excretion of bile acids and cholesterol were significantly increased and was near normal levels in DMH+BDMC-A- and DMH+curcumin-treated rats. In DMH-induced tumor bearing rats the levels of colonic and intestinal cholesterol was significantly increased whereas, the levels of phospholipid was decreased with a concomitant increase in the activities of phospholipase A (PLA) and phospholipase C (PLC), compared to untreated control rats. Intragastric administration of BDMC-A and curcumin to DMH administered rats significantly lowered the cholesterol content and raised the phospholipid content and lowered the activities of PLA and PLC towards near normal values. Our study shows that the protective effect of BDMC-A during DMH-induced colon carcinogenesis may be due to its modulatory effects on (i). histological changes, (ii). bile acids, (iii). cholesterol, and (iv). phospholipid metabolism in the target organ. Absence of histological changes in the colon of rats treated with BDMC-A, shows that long term administration of BDMC-A is nontoxic to experimental animals. Our study suggest that BDMC-A may emerge as a potent anticarcinogenic agent against colon cancer. As both BDMC-A and curcumin are equipotent in inhibiting the DMH-induced colon tumor incidence and normalizing histological changes, it could be concluded that the terminal phenolic group and the conjugated double bonds in the central seven carbon change may be responsible for the beneficial effects.     

Evaluation of amlodipine, lisinopril, and a combination in the treatment of essential hypertension

Angiotensin converting enzyme (ACE) inhibitors and dihydropyridine calcium antagonists are well established and widely used as monotherapy in patients with mild to moderate essential hypertension. Earlier studies combining short acting drugs from these classes require multiple dosing and were associated with poor compliance. Availability of longer acting compounds allows once daily administration to avoid the inconvenience of a multiple daily dose. It was decided to perform a randomised double blind, crossover study with the long acting calcium channel blocker amlodipine and the long acting ACE inhibitor lisinopril, given either alone or in combination in essential hypertension. Twenty four patients with diastolic blood pressure (DBP) between 95 and 104 mm Hg received amlodipine 2.5 mg and 5 mg, lisinopril 5 mg and 10 mg, and their combination as per a prior randomisation schedule. Supine and standing blood pressure and heart rate were recorded at weekly intervals. Higher doses of both the drugs individually or in combination were used if the target supine DBP below 90 mm Hg was not achieved. There was a significant additional blood pressure lowering effect with the combination when compared either with amlodipine or lisinopril alone. Five mg amlodipine and 10 mg lisinopril monotherapy achieved the target blood pressure in 71% and 72% patients respectively. The combination of 2.5 mg amlodipine with 5 mg lisinopril produced a much more significant lowering of blood pressure in a higher percentage of patients than that with an individual low dose.     

Incomplete hypospadiac urethral duplication with posterior urethral valves

Urethral duplication (UD) is an uncommon malformation. Obstruction rarely occurs in hypospadiac UD. We describe two children with incomplete hypospadiac UD in association with posterior urethral valves, a combination not previously recognised. The embryonic significance of this anomaly is discussed. Accepted: 30 September 1997     

Primary rhabdomyosarcoma of the larynx

Sarcomas constitute fewer than 1% of the head and neck cancers. They represent less than 1% of laryngeal cancers. Primary rhabdomyosarcoma of the larynx is an extremely rare malignancy. The available literature on this medical oddity is in the form of isolated case reports only. The purpose of this article is to add another case of primary rhabdomyosarcoma of a rare site, the larynx, of which only 36 cases have so far been reported in the world literature. The present patient, an eighteen-year-old boy is only the third case being reported from India among all reported cases of rhabdomyosarcoma of the larynx in the world literature.     

Increased susceptibility to vancomycin-resistant Enterococcus intestinal colonization persists after completion of anti-anaerobic antibiotic treatment in mice.

BACKGROUND: Antibiotic-associated disruption of the indigenous intestinal microflora may persist beyond the treatment period. Although piperacillin/tazobactam inhibits the establishment of vancomycin-resistant Enterococcus (VRE) stool colonization in mice during treatment, we hypothesized that this agent and other anti-anaerobic antibiotics would increase susceptibility to colonization during the period of recovery of the intestinal microflora. DESIGN: Mice received 10(4) colony-forming units of vancomycin-resistant E. faecium by orogastric inoculation 2, 5, or 10 days after completing 5 days of subcutaneous antibiotic treatment, or both during and 2 days after the completion of treatment. Denaturing gradient gel electrophoresis (DGGE) was performed to assess changes in the intestinal microflora. RESULTS: Anti-anaerobic antibiotics (ie, piperacillin/ tazobactam, cefoxitin, and clindamycin) caused significant disruption of the indigenous microflora (mean DGGE similarity indices < or = 27% in comparison with saline controls) and promoted the establishment of high-density colonization when VRE was inoculated 2 or 5, but not 10, days following treatment (P < .001). Piperacillin/tazobactam exhibited a biphasic effect on the establishment of colonization (ie, inhibition when exposed to VRE during treatment and promotion when exposed to VRE after discontinuation of treatment), resulting in greater overall promotion of colonization than did agents with minimal anti-anaerobic activity (ie, levofloxacin, cefepime, and aztreonam) when VRE was inoculated both during and 2 days after treatment (P < .001). CONCLUSION: Patients receiving anti-anaerobic antibiotics, including piperacillin/tazobactam, may be susceptible to the establishment of high-density VRE colonization during the period of recovery of the anaerobic microflora.