A comparative study of central versus posterior approach for internal jugular hemodialysis catheter insertion.

Internal jugular (IJ) catheter insertion for hemodialysis (HD) is an indispensable procedure in the management of patients with renal failure. The central approach is favored over posterior approach to insert IJ catheters. There are no studies comparing the outcomes between the two approaches. The aim of this study was to compare central approach with posterior approach for IJ HD catheter insertion and to analyze various outcomes like procedure-related complication rates, catheter insertion failure rates, interruptions during dialysis due to blood flow obstruction and catheter infection rates between the two methods among patients receiving HD. All patients requiring IJ HD catheter insertion during a 1-month period were randomly assigned to undergo catheter insertion via either conventional central approach or posterior approach. Patients were followed-up till the removal of the catheter. Among 104 patients included in the study, 54 were assigned to the central approach group and 50 to the posterior approach group. The central approach group had higher rate of procedure-related complications (14.81% vs. 6%, P = 0.04). Catheter insertion failure rates were marginally higher in posterior approach group (20% vs. 12.96%, P = 0.07). One or more instance of interruption during HD due to obstruction in blood flow was more common in posterior approach (46% vs. 9.25%, P < 0.01). Catheter infection rates were similar between the two groups; 16.66% (n = 9) in central group vs. 14% (n = 7) in posterior group. Posterior approach is a reasonable alternative to conventional central approach in IJ cannulation for HD catheter. It is, however, associated with a significantly high rate of interruption in HD blood flow and catheter insertion failure rates. The posterior approach can be used in patients with local exit site infection or in failed attempts to cannulate IJ vein via the conventional central approach.

Long-term carcinogenicity of pan masala in Swiss mice.

Carcinogenicity of pan masala, a dry powdered chewing mixture of areca nut, catechu, lime, spices and flavoring agents was evaluated by means of the long-term animal bio-assay 6- to 7-week old male and female S/RVCri mice were divided randomly into intermediate and lifetime exposure groups and fed normal diet without pan masala-(zero dose) or diet containing 2.5% and 5% pan masala. Animals in the intermediate-exposure group (n = 10/gender/dose group) were killed after 6, 12 or 18 months of treatment, while those in the lifetime-exposure group (n = 54/gender/dose group) were killed when moribund or at the termination of the experiment at 24 months. Several tissues were processed for histopathological examination. The body weight and survival rate of mice fed pan masala were lower than that of the controls. Histopathological observations of tissues from control animals did not reveal any neoplastic alterations. However, lifetime feeding of pan masala induced adenoma of the liver, stomach, prostate and sebaceous glands, also forestomach papilloma, liver hamartoma, hepatoma and hemangioma, carcinoma of the forestomach, adenocarcinoma of the lung and liver, and testicular lymphoma. Neoplastic lesions appeared mainly in the liver (n = 13), stomach (n = 3) and lung (n = 8). Lung adenocarcinoma, the most frequent malignant tumor type, was observed in 2/120 mice in the intermediate-exposure group and in 8/216 animals in the lifetime-exposure group. Statistical analysis of tumor-induction data revealed a significant dose-related increase in lung adenocarcinomas but not in liver and stomach neoplasms indicating that lung is the major target tissue for the carcinogenic action of pan masala.

Evaluation of carcinogenic/co-carcinogenic activity of a common chewing product, pan masala, in mouse skin, stomach and esophagus.

Pan masala, a dry powdered mixture of areca nut, catechu, lime, unspecified spices and flavoring agents, has gained widespread popularity as a chewing substitute in India. In this study, the carcinogenic and tumor-promoting potential of an ethanolic pan masala extract (EPME) was determined using skin of S/RVCri-ba mice and forestomach and esophagus of ICRC mice as the target tissues. Carcinogenic activity of pan masala was tested by painting the mouse skin for 40 weeks with EPME or by gavage feeding for 6 months. Following initiation with 9,10-dimethylbenz(a)anthracene (DMBA), carcinogenesis of mouse skin was promoted with different doses of EPME, while gastric- and esophageal-tumor-promoting activity was determined by administering EPME by gavage to animals initiated with diethylnitrosamine (DEN). The ability of EPME to effect progression of skin papilloma to carcinoma and cutaneous alterations after a single or multiple EPME treatment were also evaluated. EPME at 25 mg per dose promoted skin-papilloma formation between 30 and 40 weeks of treatment and enhanced the rate of conversion of papilloma to carcinoma. Induction of mild epidermal hyperplasia, dermal edema, increase in epidermal mitotic activity and the rate of epidermal and dermal DNA synthesis by EPME correlated well with its skin-tumor-promoting potential. In ICRC mice, EPME was inactive as a complete carcinogen, but effectively promoted the development of forestomach and esophageal papilloma and carcinoma in a concentration-dependent manner. The tumor incidence at 25 mg EPME per dose was comparable with that obtained in the 12-O-tetradecanoylphorbol-13 acetate(TPA)-treated group. The findings indicate that habitual pan-masala use may exert carcinogenic and co-carcinogenic influence.

Mutagenicity and carcinogenicity of tea, Camellia sinensis.

Aqueous, caffeine free and tannin fractions of commercial tea and tannic acid were tested for mutagenicity in Ames test. Tea fractions of tannic acid were non mutagenic in strains TA 100, TA 98, TA 1535 and TA 1538 of Salmonella typhimurium with or without metabolic activation (rat-S9 mix) at different doses tested. In strain TA 98 the above tea fractions and tannic acid inhibited the S9 mix mediated mutagenicity of tobacco in a dose dependent manner. The different tea fractions at 60 degrees C, did not increase the tumor incidence in Swiss mice by gavage feeding. They also failed to produce tumors when injected subcutaneously. Caffeine free tea extract decreased the tobacco induced liver tumors but had no effect on lung tumors. The same fraction was ineffective in hexachlorocyclohexane induced liver tumors in Swiss mice.

Hydroxychavicol: a new anti-nitrosating phenolic compound from betel leaf.

Hydroxychavicol and eugenol are the phenolic compounds isolated from betel leaf (piper betel). The modulation of nitrosation of methylurea by sodium nitrite at pH 3.6 and 30 degrees C was studied. The formation of mutagenic N-nitrosomethylurea was monitored by checking the mutagenicity of reaction mixture in Salmonella typhimurium strain TA100 and TA1535 without S9 mix. Hydroxychavicol and eugenol exhibit dose-dependent suppression of nitrosation in vitro without affecting the survival of the bacteria. Pre- or post-treatment of bacterial cells from S. typhimurium strains TA100 and TA1535 with phenolics did not modify the mutagenicity of nitrosomethylurea. The blocking of hydroxy group(s) in the benzene ring by acetylation abolishes the anti-nitrosating activity of the molecule(s). The nitrosation inhibition by hydroxychavicol is through scavenging of nitrite ions in the media, thus making them non-available for the nitrosation of methylurea.

Curcumins as inhibitors of nitrosation in vitro.

The effects of turmeric extract and its pure yellow pigments curcumin I, II and III were tested on the nitrosation of methylurea by sodium nitrite at pH 3.6 and 30 degrees C. The nitrosomethylurea formed was monitored by checking the mutagenicity in S. typhimurium strains TA1535 and TA100 without metabolic activation. Turmeric extract as well as curcumins exhibit dose-dependent decreases of nitrosation. Curcumin III was the most effective nitrosation inhibitor among the compounds tested. The simultaneous treatment of inhibitor with nitrosation precursors was essential and pre- or post-treatment of inhibitor had no effect on the mutagenicity of nitrosomethylurea. The binding of nitrite with the inhibitors was studied at pH 3.6 and 30 degrees C. Curcumin I shows a dose-dependent depletion of nitrite ions thus making nitrite non-available for nitrosation. Curcumin I and III when tested also showed a time-dependent depletion of nitrite ions at pH 3.6 and 30 degrees C. Curcumin III has a higher affinity for nitrite ions than curcumin I.

Catechin as an antimutagen: its mode of action.

In the present study, we report that the betel quid ingredient catechu, its extract and pure principle catechin were nonmutagenic in Salmonella typhimurium TA 100, TA 1535, TA 98, and TA 1538 assays with or without metabolic activation. They also exhibited dose-dependent decreases in mutagenicity of benzo(a)pyrene [B(a)P] and dimethylbenz(a)anthracene (DMBA) in strain TA 98 with metabolic activation. We further report that these compounds inhibited activities of cytochrome P-450 and had no effect on glutathione-S-transferase but increased the glutathione content in rat liver tissue. Simultaneous treatment of catechin prevented the mutagenic activity of B(a)P and DMBA metabolites in strain TA 98 in the absence of metabolic activation. Pre- and post-treatment of bacteria with catechin had no effect on the mutagenicity of B(a)P and DMBA metabolites. Catechin also inhibited the in vitro binding of 3H-B(a)P metabolites to calf thymus DNA. Catechu extract and catechin inhibited the nitrosation of methylurea by nitrite at pH 3.6 and 30 degrees C. The formation of nitrosomethylurea in the reaction mixture was monitored by measuring the histidine revertants of strain TA 1535 in the absence of metabolic activation. Pre- and post-treatment of catechu extract or catechin had no effect on the mutagenicity of nitrosomethylurea in TA 1535. The nitrosation inhibition by catechin was through scavenging of nitrite observed at pH 3.6. The above study indicates that catechu in betel quid may act as an antimutagen and may suppress the mutagenic potential of other betel quid mutagens.

Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens.

Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.

Hydroxychavicol: a new phenolic antimutagen from betel leaf.

The phenolic compounds eugenol and hydroxychavicol were separated from betel leaf extract using C18 phase bonded Hiflosil silica gel. The structures of the two compounds were confirmed by nuclear magnetic resonance data. Neither eugenol nor hydroxychavicol was mutagenic when tested in various strains of Salmonella typhimurium with or without metabolic activation. Both compounds exhibited dose-dependent suppression of dimethylbenzanthracene-induced mutagenesis in S. typhimurium strain TA98 with metabolic activation. Hydroxychavicol was more potent than eugenol in this respect.

In vitro cultivation of embryonic rat tongue cells--a convenient system for oral carcinogenesis studies.

Fine mince of embryonic rat tongue suspended in medium and transferred to culture vessel adhere immediately to surface. Epithelial and fibroblastic cell outgrowth seen in the first few days was overgrown with fibroblasts later. Evidence is presented that these fibroblasts are sensitive to post-confluence inhibition of division and exhibit several properties of normal fibroblasts including limited lifespan. This system may serve as a simple in vitro model for oral carcinogenesis studies.