Haplotype and genotype effects of the F7 gene on circulating factor VII,coagulation activation markers and incident coronary heart disease in UK men

Background: Evidence for the associations of single nucleotide polymorphisms (SNPs) in the F7 gene and factor (F)VII levels and with risk of coronary heart disease (CHD) is inconsistent. We examined whether F7 tagging SNPs (tSNPs) and haplotypes were associated with FVII levels, coagulation activation markers (CAMs) and CHD risk in two cohorts of UK men. Methods: Genotypes for eight SNPs and baseline levels of FVIIc, FVIIag and CAMs (including FVIIa) were determined in 2773 healthy men from the Second Northwick Park Heart Study (NPHS‐II). A second cohort, Whitehall II study (WH‐II, n = 4055), was used for replication analysis of FVIIc levels and CHD risk. Results: In NPHS‐II the minor alleles of three SNPs (rs555212, rs762635 and rs510317; haplotype H2) were associated with higher levels of FVIIag, FVIIc and FVIIa, whereas the minor allele for two SNPs (I/D323 and rs6046; haplotype H5) was associated with lower levels. Adjusted for classic risk factors, H2 carriers had a CHD hazard ratio of 1.34 [95% confidence interval (CI): 1.12–1.59; independent of FVIIc], whereas H5 carriers had a CHD risk of 1.29 (95% CI: 1.01–1.56; not independent of FVIIc) and significantly lower CAMs. Effects of haplotypes on FVIIc levels were replicated in WH‐II, as was the association of H5 with higher CHD risk [pooled‐estimate odds ratio (OR) 1.16 (1.00–1.36), P = 0.05], but surprisingly, H2 exhibited a reduced risk for CHD. Conclusion: tSNPs in the F7 gene strongly influence FVII levels. The haplotype associated with low FVIIc level, with particularly reduced functional activity, was consistently associated with increased risk for CHD, whereas the haplotype associated with high FVIIc level was not.     

Can the Immunobead Assay for Detecting Sperm Antibodies in Fresh Samples Be Reproduced in Cryopreserved/Thawed Human Spermatozoa?

PROBLEM : To evaluate the reproducibility of the Immunobead Assay (IBA) on sperm samples before and after cryopreservation. METHOD : Sperm samples (fresh and post-thaw) from known antibody negative donors (N=20) were evaluated for percent immunobead binding by IBA following incubation with known antibody-positive serum. RESULTS : In both fresh and thawed negative samples, the mean sperm head binding was 0.5% ± 0.5, the mean sperm tail binding was 2.0% ± 2.0 and the mean sperm head-tail binding was 3.0% ± 2.0 for IgG, IgA and IgM type antibodies, respectively. The same samples exposed to positive sera showed 40.0% ± 10.0 mean head binding, 7.0% ± 8.0 mean tail binding and 47.0% ± 11.0 mean head-tail binding. CONCLUSIONS : IBA is highly reproducible for detecting sperm antibodies in both fresh and cryopreserved/thawed samples of human spermatozoa.     

Screening of Antioxidant Potential of Selected Barks of Indian Medicinal Plants by Multiple in vitro Assays LI

Objective To evaluate the antioxidant potential in herbal extract barks of five therapeutically important medicinal plants native to India,i.e.Crataeva nurvala Buch.-Ham.,Buchanania lanzan Spreng.,Aegle marmelos Corr.,Dalbergia sissoo Roxb.ex DC.,and Cedrela toona Roxb.Methods Standardized aqueous alcoholic extracts from the selected barks having different target radicals,such as superoxide radical,nitric oxide,ABTS radical,and peroxidative decomposition of phosphohpids.were prepared and screened bv multiple in vitro assays.These extracts were also tested for total phenolic and tannin content and correlated with antioxidant capacity. Results Tbtal phenolic and tannin contents were found to be the highest in C. nurvala (195 GAE mg/g and 218.3 mg/g CE).SOD mimetic activity was found to be the highest in Crataeva nurvula,although all barks showed activity more than 100 units/mg extract.Lipid peroxidation inhibitory potential was found to be the highest in Crataeva nurvala(83.4% inhibition of MDA formation/10 μg extract),and also showed a comparatively high NO quenching capacity (45.5% per 10 μg extract).The highest NO quenching potential was found in Aegle marmelos(47.3% per 10 μg extract).Cedrela toona showed the lowest LPO inhibitory potential and NO quenching capacity(50.5% and 30.5%,respectively).Buchanania lanzan,a medicinal plant extensively used for inflammatory disorders and Dalbergia sissoo also showed 72.5% and 69.1% LPO inhibitory potential/10 μg extract.Trolox equivalent antioxidant capacity ranged from 0.24 to 0.39 mmol/L TEAC/mg extract,indicating that all the barks tested had ABTS radical quenching capacity.Conclusion Bark of Crataeva nurvulahas the highest antioxidant capacity and a positive correlation between antioxidant activity and their plendic content was found.     

CRUSTED SCABIES: AN UNUSUAL CLINICAL MANIFESTATION

The patient, a 40-year-old Brazilian woman, was admitted to the Pernambuco Federal University Hospital with a dry extensive crusted eruption on her skin. She had a history of uterine carcinoma that had been treated by radiotherapy 3 years before. She had been losing weight for the past few years. The patient's husband had ordinary scabies, and the family history revealed other affected members. Her bed linen was always covered with scales.
Physical examination revealed generalized cutaneous erythema and scaling. The palms were markedly hyperkera-totic (Figs. 1 and 2). This caused discomfort under pressure. There was a mild pruritus and her nails were abnormal. No burrows or vesicles were seen.
Laboratory studies revealed the following: anemia and eosinophilia of 12%. Immunoglobulins were normal. Her cel-lular immunity was diminished. Sensitivity to dinitrochloro-benzene and reactivity to intradermal injection of tuberculin, trichophytin, and candidin were negative. Direct light mi-croscopy of thick scales showed a large number of Sarcoptes mites and numerous eggs. Microscopic examination of a biopsy specimen showed hyperkeratosis, acanthosis, and a chronic inflammatory infiltrate composed predominantly of lymphoid cells. The horny layer was riddled with innumer-able mites.
The patient was treated with a 20% urea ointment and 1% lindane lotion. The skin condition was significantly im-proved after a 5-day treatment with keratolytic ointment (2 times a day) and antiscabic lotion applied at night to the whole skin for a period of 5 days. Throughout the hospital stay she remained in good health and was discharged 10 days after admission with her dermatologic problem com-pletely cured (Fig. 3).
Four months later the patient died due to a cerebral metastatic carcinoma.