Evaluation of the contribution of smoking to total blood polonium-210 in Saudi population.

A preliminary study of 210Po concentrations in the blood of some smokers and nonsmokers is presented in order to evaluate the contribution of smoking to total blood 210Po in Saudi population. Blood samples were collected from 30 volunteers and analyzed by high resolution alpha-spectrometry using a radiochemical technique. The technique is based on the separation of polonium from other components of the sample by wet ashing with an HNO3/H2O2 oxidizing mixture and spontaneous deposition on a silver disc under the relevant conditions for alpha-particle counting. The results indicated that a significant fraction (about 30%) of blood 210Po is related to smoking.     

Manzamine B and E and ircinal A related alkaloids from an Indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and Alzheimer's diseases

Four new manzamine-type alkaloids, 12,28-oxamanzamine E (2), 12,34-oxa-6-hydroxymanzamine E (3), 8-hydroxymanzamine B (5), and 12,28-oxaircinal A (11), were isolated from three collections of an Indonesian sponge of the genus Acanthostrongylophora together with 13 known manzamine alkaloids, ircinal A, ircinol A, xestomanzamine A, manzamines A, E, F, J, and Y, manadomanzamines A and B, neo-kauluamine, 8-hydroxymanzamine A, and manzamine A N-oxide. The structures of the new compounds were elucidated by means of 1D and 2D NMR spectroscopic methods. Three of these compounds (2, 3, and 11) possess a unique manzamine-type aminal ring system generated through an ether linkage between carbons 12-28 or between carbons 12-34. In the case of manzamine B and related metabolites, carbons 11 and 12 of the typical manzamine structure have an epoxide group and add to our growing understanding of manzamine structure-activity relationships (SAR) and metabolism. The bioactivity and SAR for a number of previously reported manzamine-related metabolites against malaria, leishmania, tuberculosis, and HIV-1 are also presented. Manzamine Y (9) showed significant inhibitory activity of GSK3, an enzyme implicated in Alzheimer's disease pathology. The toxicity of manzamine A and neo-kauluamine was evaluated against both medaka fry and eggs.     

Aromatic constituents of Uvaria grandiflora

Grandiuvarone A (1) and grandiuvarins A-C (2-4) were isolated from the bark of Uvaria grandiflora. The structures of these new aromatic compounds were elucidated on the basis of spectroscopic analyses, especially 2D NMR techniques. Only compound 1 exhibited antileishmanial activity, with IC(50)/IC(90) values of 0.7/1.5 microg/mL. The positive controls pentamidine and amphotericin B had IC(50)/IC(90) values of 1.6/6.6 and 0.17/0.34 microg/mL, respectively.     

Racial differences in prevalence of a supratypic HLA-genetic marker immaterial to pre-employment testing for susceptibility to chronic beryllium disease

BACKGROUND: A beryllium materials manufacturer is conducting a limited pilot program that offers testing for HLA-DP beta 1E69 with genetic counseling through a third party to applicants for employment. An important consideration in this regard is the prevalence of this marker in the general population, and its consequent positive predictive value of disease susceptibility. METHODS: Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine HLA-DP beta 1E69 population frequencies. Estimation of positive predictive values assumed a disease frequency among beryllium workers of either 5 or 15% and used an odds ratio for disease risk of 35 for the HLA-DP beta 1E69 marker. RESULTS: Allelic/carrier frequencies were found to be 0.21/0.33, 0.24/0.40, 0.27/0.47, and 0.38/0.59 for Caucasians, African-Americans, Hispanics, and Chinese, respectively. Ranges of positive predictive values for a genetic test based on HLA-DP beta 1E69 in these populations were calculated to be 8.3-14.3% for carriers with an assumed disease frequency of 5%. For high risk subgroups with disease frequencies of 15%, the range of positive predictive values was found to span between 24.9-43.0%. CONCLUSIONS: These estimates suggest that using HLA-DP beta 1E69 genotyping for general pre-employment screening in the beryllium industry has a low positive predictive value, which varies little among racial groups where carrier frequencies differ significantly.     

DNA Sequence Variation and Haplotype Structure of the ICAM1 and TNF Genes in 12 Ethnic Groups of India Reveal Patterns of Importance in Designing Association Studies

We have examined the patterns of DNA sequence variation in and around the genes coding for ICAM1 and TNF, which play functional and correlated roles in inflammatory processes and immune cell responses, in 12 diverse ethnic groups of India. We aimed to (a) quantify the nature and extent of the variation, and (b) analyse the observed patterns of variation in relation to population history and ethnic background. At the ICAM1 and TNF loci, respectively, the total numbers of SNPs that were detected were 28 and 12. Many of these SNPs are not shared across ethnic groups and are unreported in the dbSNP or TSC databases, including two fairly common non‐synonymous SNPs at positions 13487 and 13542 in the ICAM1 gene. Conversely, the TNF‐376A SNP that is reported to be associated with susceptibility to malaria was not found in our study populations, even though some of the populations inhabit malaria endemic areas. Wide between‐population variation in the frequencies of shared SNPs and coefficients of linkage disequilibrium have been observed. These findings have profound implications in case‐control association studies.     

Corticosterone response in the chick separation-stress paradigm

Corticosterone response to separation stress and its sensitivity to the anxiolytic, chlordiazepoxide (CDP), were examined in 7-day-old domestic fowl (Gallus gallus). Saline or CDP (8.0 mg/kg) was injected intramuscularly 30 min before tests. Chicks were placed in isolation either with or without mirrors for a 15-min observation period, in which distress vocalizations were recorded. After testing, chicks were euthanized and blood was collected for the corticosterone assay. Chicks tested in the No-Mirror condition displayed an increase in vocalizations that was attenuated by CDP. Similarly, corticosterone levels were highest in chicks tested in the No-Mirror condition; however, CDP only modestly attenuated corticosterone levels. The present findings demonstrate that corticosterone levels parallel the behavioral marker of distress vocalizations in this paradigm, but this biological marker may be less sensitive than the behavioral marker to benzodiazepine anxiolytic manipulations.