Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the caspase 9- and caspase 3-dependent pathway

Anti-recoverin autoantibodies have been associated with cancer-associated retinopathy (CAR), a paraneoplastic blinding disease. Those antibodies have been shown to induce apoptotic death of photoreceptor cells. The objective was to ascertain the mechanisms of retinal death induced by anti-recoverin antibody in vitro by examining the apoptotic pathway involved in retinal cell death. Internalization of anti-recoverin antibody or its Fab fragments by retinal cells mediated by endocytosis lead to cytotoxicity. Antibody cellular translocation induced the increase of bcl-x(s) and bax and the decrease in the bcl-x(L) protein. We detected the release of cytochrome c and down-regulation of the apaf-1 protein. This correlated with the sequential activation of caspase 9 and caspase 3, as well as the degradation of the caspase substrate PARP and the fragmentation of DNA. Our data show that anti-recoverin antibodies are inducers of apoptosis through the mitochondrial pathway involving caspases 9 and 3. We propose that a similar mechanism may be in place in patients with CAR syndrome where high levels of circulating antibodies have been associated with retinal degeneration.     

CYP17 genotypes differ in salivary 17-beta estradiol levels: a study based on hormonal profiles from entire menstrual cycles.

Variation in the levels of sex-steroid hormones results from differences in developmental conditions, adult lifestyle, and genetic polymorphism. Genes involved in sex-steroid biosynthesis have been implicated to influence levels of hormones in premenopausal women, but the results were inconclusive. We tested variation among women in levels of salivary estradiol (E(2)) corresponding to CYP17 genotypes. CYP17 encodes cytochrome P450c17alpha, which mediates two enzymes important in E(2) synthesis. In contrast to the earlier studies that relied on one or a few samples for assessing the E(2) levels of an individual woman, our study is based on daily collected saliva samples for one entire menstrual cycle. Sixty Polish women, ages 24 to 36 years, with regular menstrual cycles and no reported fertility problems participated in the study. Women with A2/A2 genotype had 54% higher mean E(2) levels than women with A1/A1 genotype (P = 0.0001) and 37% higher than women with A1/A2 genotype (P = 0.0008). Heterozygous A1/A2 women had 13 % higher E(2) levels than homozygous A1/A1 women (but this difference was significant only in a nonparametric test). Levels of E(2) during the day with highest E(2) (day -1) were 72% higher in A2/A2 compared with A1/A1 (P = 0.01) and 52 % higher compared with A1/A2 (P = 0.03). Our results suggest that CYP17 genotype may serve as a biomarker of endocrine function in women of reproductive age. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2131-5).     

Determination of ochratoxin a in spices

The method of determination of ochratoxin A in some spices: coriander, cloves, ginger, paprika, black pepper was described. Depending on kind of matrix, extraction with metanol/water (80/20) or with solution of 1% NaHCO3 and several variants of clean-up on IAC columns were investigated. The most useful extraction solvent appeared water solution of 1% NaHCO3. In case of cloves only, none of the methods of extraction and clean-up variants was appropriate. The mean recovery of the method, dependent on kind of sample, was 61-82% and RSD% 1.4 and 7.8. The estimated LOD and LOQ were 0.02 and 0.06 microg/kg, respectively. In samples of spice used for method preparation, ochratoxin A was detected on the level 3.4-4.6 microg/kg.     

Fimbriae as virulence factors of uropathogenic strains of Escherichia coli

In this paper uropathogenic Escherichia coli strains are characterized. In particular, fimbrie as virulence factors are presented and their role in the clinical course of urinary tract infection is assessed.     

Peripartum cardiomyopathy--a case report

Peripartum cardiomyopathy -- a case report. A case of a 32-year old woman, previously healthy, with heart failure symptoms occurring during third pregnancy, is described. In spite of standard pharmacological treatment, her condition worsened and the pregnancy had to be terminated at 28 hbd by cesarean section. The patient's condition improved and three months later normal left ventricular function as well as good exercise tolerance were observed.