Acidic urine pH is associated with elevated levels of free urinary benzidine and N-acetylbenzidine and urothelial cell DNA adducts in exposed workers.

We evaluated the influence of urine pH on the proportion of urinary benzidine (BZ) and N-acetylbenzidine present in the free, unconjugated state and on exfoliated urothelial cell DNA adduct levels in 32 workers exposed to BZ in India. Postworkshift urine pH was inversely correlated with the proportions of BZ (r = -0.78; P < 0.0001) and N-acetylbenzidine (r = -0.67; P < 0.0001) present as free compounds. Furthermore, the average of each subject's pre- and postworkshift urine pH was negatively associated with the predominant urothelial DNA adduct (P = 0.0037, adjusted for urinary BZ and metabolites), which has been shown to cochromatograph with a N-(3'-phosphodeoxyguanosin-8-yl)-N'-acetylbenzidine adduct standard. Controlling for internal dose, individuals with urine pH < 6 had 10-fold higher DNA adduct levels compared to subjects with urine pH > or = 7. As reported previously, polymorphisms in NAT1, NAT2, and GSTM1 had no impact on DNA adduct levels. This is the first study to demonstrate that urine pH has a strong influence on the presence of free urinary aromatic amine compounds and on urothelial cell DNA adduct levels in exposed humans. Because there is evidence that acidic urine has a similar influence on aromatic amines derived from cigarette smoke, urine pH, which is influenced by diet, may be an important susceptibility factor for bladder cancer caused by tobacco in the general population.

The glutathione S-transferase M1 (GSTM1) null genotype and benzidine-associated bladder cancer, urine mutagenicity, and exfoliated urothelial cell DNA adducts.

Multiple studies in the general population have suggested that subjects with the glutathione S-transferase M1 (GSTM1)-null genotype, who lack functional GSTM1, are at higher risk for bladder cancer. To evaluate the impact of the GSTM1-null genotype on bladder cancer caused by occupational exposure to benzidine and to determine its influence on benzidine metabolism, we carried out three complementary investigations: a case-control study of bladder cancer among workers previously exposed to benzidine in China, a cross-sectional study of urothelial cell DNA adducts and urinary mutagenicity in workers currently exposed to benzidine in India, and a laboratory study of the ability of human GSTM1 to conjugate benzidine and its known metabolites in vitro. There was no overall increase in bladder cancer risk for the GSTM1-null genotype among 38 bladder cancer cases and 43 controls (odds ratio, 1.0; 95% confidence interval, 0.4-2.7), although there was some indication that highly exposed workers with the GSTM1-null genotype were at greater risk of bladder cancer compared to similarly exposed workers without this allele. However, the GSTM1 genotype had no impact on urothelial cell DNA adduct and urinary mutagenicity levels in workers currently exposed to benzidine. Furthermore, human GSTM1 did not conjugate benzidine or its metabolites. These results led us to conclude that the GSTM1-null genotype does not have an impact on bladder cancer caused by benzidine, providing a contrast to its association with elevated bladder cancer risk in the general population.

Carcinogen exposure and effect biomarkers.

Monitoring for occupational exposures to carcinogens can be among the most daunting tasks of the occupational health professional. Air sampling data do not provide reliable estimates of exposure because the skin is often a major route of entry. Biological monitoring markers are available on several levels for chemical carcinogens, however. These can be used to augment the occupational health program by providing estimates of internal and effective dose. Carcinogen biomarkers have proven to be important tools in research studies of exposure and genetic susceptibility. The results of two of these studies will be reviewed and placed in the context of an occupational monitoring program. We found that a battery of markers was very useful in a cross-sectional study. Individuals with high exposure and effect could be identified as were physiological factors which caused higher levels of effective dose markers.

Effect of selected pesticides on alkaline and acid phosphatase in the rat.

A single oral dose of DDT (60.0 mg/kg), malathion (687.5 mg/kg), phosalone (60.0 mg/kg) and elsan (175.0 mg/kg) to adult male albino rats produced significant impairment in acid and alkaline phosphatase activities within 1 h of dosing. Renal and hepatic alkaline phosphatase activity was significantly inhibited in all cases, while treatment with malathion and phosalone resulted in an increase in intestinal alkaline phosphatase activity. Elsan induced an increase in acid phosphatase activity in liver, kidney and intestine whereas the response to DDT, malathion and phosalone was variable.

Survey amongst workers in pesticide factories.

Blood samples of 75 pesticide factory workers in Agra Division, India, were analyzed for biochemical parameters of clinical importance. About 75% of the subjects had significantly low levels of serum cholinesterase activity. Several subjects had below average blood sugar and urea values. The majority had elevated levels of serum cholesterol, phospholipid and SGOT activity. 52 workers reported general toxic symptoms. A correlation between the clinical manifestations and blood biochemical parameters has been attempted.

Benzidine-DNA adduct levels in human peripheral white blood cells significantly correlate with levels in exfoliated urothelial cells.

In a cross-sectional study of 33 workers exposed to benzidine and benzidine dyes and 15 non-exposed controls, we previously reported that exposure status and internal dose of benzidine metabolites were strongly correlated with the levels of specific benzidine-DNA adducts in exfoliated urothelial cells. We also evaluated DNA adduct levels in peripheral white blood cells (WBC) of a subset of 18 exposed workers and 7 controls selected to represent a wide range of adducts in exfoliated urothelial cells. Samples were coded and then DNA was analyzed using 32P-postlabeling, along with n-butanol extraction. One adduct, which co-chromatographed with a synthetic N-(3'-phospho-deoxyguanosin-8-yl)-N'-acetylbenzidine standard, predominated in those samples with adducts present. The median level (range) of this adduct in WBC DNA was 194.4 (3.2-975) RAL x 10(9) in exposed workers and 1.4 (0.1-6.4) in the control subjects (p = 0.0002, Wilcoxon Rank Sum Test). There was a striking correlation between WBC and exfoliated urothelial cell adduct levels (Pearson r = 0.84, p < 0.001) among exposed subjects. In addition, the sum of urinary benzidine, N-acetylbenzidine and N,N'-diacetylbenzidine correlated with the levels of this adduct in both tissues. This is the first study in humans to show a relationship for a specific carcinogen adduct in a surrogate tissue and in urothelial cells, the target for urinary bladder cancer.

Cardiac toxicity following short-term exposure to methomyl in spraymen and rabbits.

A health surveillance study in 22 healthy spraymen showed significant T-wave changes (including inversion) in most of the limb leads and chest leads following 5 d exposure to methomyl, a carbamate pesticide. Significant changes in plasma cholinesterase and lactic dehydrogenase activities were also noticed. The ECG changes could be reproduced in rabbits and were dose dependent. This type of ECG change following exposure to a carbamate compound is reported for the first time in occupationally-exposed subjects. The study results indicate that these changes are probably directly related to methomyl rather than its toxicity through cholinesterase inhibition. The significance of these changes remain to be investigated.

Assessment of thyroid function in pesticide formulators.

Thirty male pesticide formulators exposed to the dust and liquid formulation of endosulfan, quinalphos, chlorpyriphos, monocrotophos, lindane, parathion, phorate, and fenvalerate and 20 comparable control subjects from the same area of study were examined for the evaluation of thyroid function tests. The level of TSH was elevated (about 28%) in pesticide formulators as compared to a control group, but the increase was statistically insignificant. Based on the individual TSH measurement, 3 of 30 formulators had isolated elevated levels of TSH and seem to have acquired sub-clinical hypothyroidism; five had TSH values slightly elevated to the upper boarder line (4.03 muIU/ml); and the majority of formulators (N= 22) had TSH values in the normal range varying from 1.29 to 3.9 muIU/ml. Total T3 was suppressed significantly (P< 0.01) in formulators, while marginal decrease (about 7%) was noticed in T4 level. This study indicated thyroid function impairment in few pesticide formulators.

Spectral evidence for the oxidation of beta-hydroxybutyrate to acetoacetate: diminution of spectra by glucose and chloride.

Chemical oxidation of beta-hydroxybutyrate (beta-OHB) to acetoacetate (AcAc) has been carried out by a simple and new method employing potassium persulphate as an oxidising agent. Under the conditions of assay, beta-OHB (0.079-0.395 microM) was instantaneously oxidised to AcAc and the authenticity of the oxidised product was proved by absorption spectroscopy. A common absorption maxima at about 446 nm was observed in all the spectra recorded for the product (AcAc-complex) obtained after the oxidation of beta-OHB (0.079-0.395 microM) to AcAc followed by coupling with diazotized p-nitroaniline. This absorption maxima was almost equal to that obtained for AcAc-complex using AcAc as reference standard. It implies that AcAc formed by the chemical oxidation of beta-OHB is identically similar to the AcAc used as reference standard for the study. This fact was further strengthened when absorption spectra, recorded either individually or in combination (mixed-type), exhibited a single peak with a common absorption maxima at about 446 nm. Absorption spectra was found to be partially diminished by glucose (1.77 microM) and chloride (17.1 microM), while almost complete diminution of absorption spectra was observed at higher concentration of glucose (8.88 microM) and chloride (51.3 microM).

Pioneers of Ayurveda during Nizam-VII.

This article is the continuation of the article entitled "Dawn of Ayurveda during the reign of Nizam-VII of, Hyderabad" published in B.I.I.H.M. Vol. 18, No. 1, Jan 1998, pp. 67-84. The life sketch of nine pioneers of Ayruveda who established the system of Ayurveda on the track during the rule of Nizam - VII - Mir Osman Ali Khan Bahadur are presented here.

Eminent ayurvedic physicians of Nizam dynasty.

It is a biographical work which sheds light on the lives and works of some of the Ayurvedic Physicians flourished during Nizam dynasty. The credit for development of Ayurveda in Hyderabad goes to the eminent Ayurvedic Physicians, mentioned in this articles who taught Ayurveda in their private clinics, rendered their services during the outbreak of epidemics, organised conferences, compiled very useful works on Ayurveda and established an Ayurvedic school on a grand scale which was recognised by the government.

Lesser known Ayurvedic physicians of India from an Urdu book- "Rumoozul Atibba".

In early 20th century some Urdu scholars tried to enrich urdu literature with medical history. They started compiling and publishing the biographies of the contemporary physicians along with their achievements. One of such works "Rumoozul Atibba" a rare book compiled by Hakim Fairozuddin in Urdu, published by 'Darul Kutub Rafiqul Atibba' and printed in 'Rifah-e-Aam Press' at Lahore in the year 1913 A.D. has been taken here. It contains about 150 short biographies of Ayurvedic and Unani physicians, out of which all the twenty biographies of Ayurvedic physicians given in it, have been presented in this article.