Smoking habits, signs of chronic diseases and survival in inland and coastal regions of Croatia: a follow-up study

Aim of the study was to estimate, the relationship between survival, smoking habits, and the results of medical examinations in inland and coastal regions of Croatia. Age and sex stratified sample of general population (1,571 men and 1,793 women, 37-56 years old in 1972; followed in 1982: N = 1,090 men; 1,325 women and/or 1972-1999 controlling vital status). Relative risks and 95% confidence limits were estimated using Cox regression in the model with time dependent covariates, separately by sex. In all regions, the proportion of male smokers decreased between 1972 and 1982. The proportion of female smokers increased, differently in urban and rural regions. During the follow-up between 1972 and 1999, 568 deaths were recorded among men and 382 among women. In men, in addition to age, significant hazards of death were the number of smoked cigarettes per day, body mass index, sedative intake, vital lung capacity (FVC), 100FEV1/VC, systolic blood pressure, electrocardiogram, history of heart attack, and region. In women, in addition to age, significant predictors were the number of smoked cigarettes per day, systolic blood pressure, electrocardiogram, history of heart disease (excluding coronary diseases), and region. Survival relative risk increased with each additional smoked pack of cigarettes by 2.4% in women and 1.3% in men. Regional differences vs. smoking habit were observed. These data emphasize the need for prevention of smoking.     

Estrogen suppresses IL-1beta-mediated induction of COX-2 pathway in rat cerebral blood vessels

Interleukin (IL)-1beta is a potent inducer of inflammatory prostaglandins, which are important mediators of vascular response to cerebral injury, whereas estrogen reduces brain injury in models of ischemic stroke. Thus we examined the effects of in vivo IL-1beta exposure on cerebrovascular cyclooxygenase (COX)-2 expression and function in an animal model of chronic estrogen replacement. Estrogen-treated and nontreated ovariectomized female rats received IL-1beta injections (10 microg/kg i.p.), and then cerebral vessels were isolated for biochemical and contractile measurements. In estrogen-deficient rats, IL-1beta induced cerebrovascular COX-2 protein expression; a peak response occurred 3 h after injection. COX-2 was localized to arterial endothelium using confocal microscopy. IL-1beta increased PGE2 but not PGI2 production and decreased vascular tone as measured in isolated cerebral arteries; the latter effect was partially reversed by treatment with the selective COX-2 inhibitor NS-398 (10 micromol/l). In contrast, in animals treated with estrogen, IL-1beta had no significant effect on COX-2 protein levels, PGE2 production, or vascular tone. Combined treatment with 17beta-estradiol and medroxyprogesterone acetate also prevented increases in PGE2 production after IL-1beta treatment, but treatment with 17alpha-estradiol had no effect. IL-1beta induction of COX-2 protein was prevented by treatment with the nuclear factor-kappaB inhibitor caffeic acid phenethyl ester (20 mg/kg i.p.), and estrogen treatment reduced cerebrovascular nuclear factor-kappaB activity. Estrogen thus has potent anti-inflammatory effects with respect to cerebral vascular responses to IL-1beta. These effects may have important implications for the incidence and severity of cerebrovascular disease.     

Central wedge nymphectomy with a 90-degree Z-plasty for aesthetic reduction of the labia minora

The labia minora or nymphae of the vulva are two cutaneous-mucosal refolds located between the labia majora, the internal aspect of which is separated by the interlabial cleft. The enlargement of the labia minora may be attributable to several factors, most commonly congenital. Although some women require surgical reduction for functional reasons, most seek reduction of their labia minora because of psychological concerns. The authors describe a modified plastic surgery procedure for functional and aesthetic reduction of the labia minora.     

Prevalence and seasonal variations of six bee viruses in Apis mellifera L. and Varroa destructor mite populations in France

A survey of six bee viruses on a large geographic scale was undertaken by using seemingly healthy bee colonies and the PCR technique. Samples of adult bees and pupae were collected from 36 apiaries in the spring, summer, and autumn during 2002. Varroa destructor samples were collected at the end of summer following acaricide treatment. In adult bees, during the year deformed wing virus (DWV) was found at least once in 97% of the apiaries, sacbrood virus (SBV) was found in 86% of the apiaries, chronic bee paralysis virus (CBPV) was found in 28% of the apiaries, acute bee paralysis virus (ABPV) was found in 58% of the apiaries, black queen cell virus (BQCV) was found in 86% of the apiaries, and Kashmir bee virus (KBV) was found in 17% of the apiaries. For pupae, the following frequencies were obtained: DWV, 94% of the apiaries; SBV, 80% of the apiaries; CBPV, none of the apiaries; ABPV, 23% of the apiaries; BQCV, 23% of the apiaries; and KBV, 6% of the apiaries. In Varroa samples, the following four viruses were identified: DWV (100% of the apiaries), SBV (45% of the apiaries), ABPV (36% of the apiaries), and KBV (5% of the apiaries). The latter findings support the putative role of mites in transmitting these viruses. Taken together, these data indicate that bee virus infections occur persistently in bee populations despite the lack of clinical signs, suggesting that colony disease outbreaks might result from environmental factors that lead to activation of viral replication in bees.     

Genetic susceptibility and risk of gastric cancer in a human population of Cauca, Colombia

Gastric cancer (GC) is the main cause of mortality by cancer in Colombia. Glutathione S-transferase (GST) enzymes are involved in the detoxification of many environmental carcinogens. The homozygous deletions of glutathione S-transferase M1 (GSTM1-0) and glutathione S-transferase T1 (GSTT1-0) have been associated with several types of cancer. The risk to develop GC has been associated with environmental factors and Helicobacter pylori infection. The tumor necrosis factor (TNF-alpha) and its levels are increased in patients infected with H. pylori. A G/ A transition in the position -308 of the promoter of the TNF-alpha has been related in several studies to an increased expression of the gene and is associated with susceptibility to GC. The association of these polymorphisms with GC and the interaction with other risk factors (life style) were investigated. Blood samples were obtained from 46 GC patients and 96 controls. The logistic regression model was used to obtain the odds ratio (OR) and their 95% confidence intervals. These statistics established the association between the enzymatic polymorphisms and GC and between other independent factors and GC. The frequency of the TNF-alpha polymorphism in people infected with H. pylori was 18% in the GC population and 7% in the control group. This transition was not significantly associated with H. pylori infection and GC. The frequencies of the deletion polymorphisms for patients and controls were as follows: GSTM1 65.2% and 37.5%; GSTT1 17.4% and 14.6%. These results suggested that the GSTM1 deletion polymorphism was associated with an increased risk of gastric cancer (OR of 5.5; 95%CI, 1.7-17.2). Furthermore, other risk factors such as H. pylori infection (OR 5.58, CI 1.8-17.2), smoking (OR 6.70, CI 2.2-20.3) and alcohol intake (OR 3.27, CI 1.1-9.4) were associated with GC.     

Lack of alterations on meiotic chromosomes and morphological characteristics of male germ cells in mice exposed to a 60 Hz and 2.0 mT magnetic field

The effect of in vivo exposure of mice to a 60 Hz sinusoidal magnetic field (MF) at 2.0 mT on male germ cells was studied. The cytological endpoints measured included meiotic chromosome aberrations in spermatocytes and sperm morphology. Three independent experiments were carried out: (a) animals exposed for 72 h, (b) 10 days/8 h daily, and (c) 72 h exposure to MF plus 5 mg/kg of Mitomycin-C. No statistically significant differences indicative of MF effects were observed between MF exposed and control animals. In addition, an opposite effect between MF exposure and Mitomycin-C treatment in terms of chromosomal aberrations and sperm morphology was observed.     

A digenic cause of cleft lip in A-strain mice and definition of candidate genes for the two loci

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate, CL(P), is a common human birth defect with a complex unknown genetic cause. The mouse model is the "A/-" strains. Our previous studies mapped two loci: clf1 on Chr11 and clf2 on Chr13--with a strong genetic maternal effect on the level of risk. Here we test the hypothesis that CL(P) is digenic and identify candidate genes for clf1 and clf2. METHODS: We observed E14 CL(P) frequencies in backcross (BC1) embryos from a new cross of A/WySn to AXB-4/Pgn and from test crosses of three new "congenic RI" lines. Using new polymorphic markers from genes and our mapping panels of segregants and RI strains, we identified the candidate genes for clf1 and clf2. We sequenced the coding region of Ptch in A/WySn cDNA. RESULTS: Seventy new BC1 CL(P) segregants (4%) were obtained, as predicted. All three new congenic RI lines homozygous for both clf1 and clf2 had A/WySn-level CL(P) frequencies (10-30%) in test crosses. The clf1 region contains 10 known genes (Arf2, Cdc27, Crhr1, Gosr2, Itgb3, Mapt, Myl4, Nsf, Wnt3, and Wnt9b). The clf2 region contains 17 known genes with human orthologs. Both regions contain additional potential genes. No causal mutation in Ptch coding sequence was found. CONCLUSIONS: In A-strain mice, nonsyndromic CL(P) is digenic, suggesting that nonsyndromic human CL(P) may also be digenic. The orthologous human genes are on 17q (clf1) and 9q, 8q and 5p (clf2), and good candidate genes are WNT3 or WNT9B (17q), and PTCH (9q) or MTRR (5p).     

Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4

The neuronal protein synaptotagmin 1 functions as a Ca(2+) sensor in exocytosis via two Ca(2+)-binding C(2) domains. The very similar synaptotagmin 4, which includes all the predicted Ca(2+)-binding residues in the C(2)B domain but not in the C(2)A domain, is also thought to function as a neuronal Ca(2+) sensor. Here we show that, unexpectedly, both C(2) domains of fly synaptotagmin 4 exhibit Ca(2+)-dependent phospholipid binding, whereas neither C(2) domain of rat synaptotagmin 4 binds Ca(2+) or phospholipids efficiently. Crystallography reveals that changes in the orientations of critical Ca(2+) ligands, and perhaps their flexibility, render the rat synaptotagmin 4 C(2)B domain unable to form full Ca(2+)-binding sites. These results indicate that synaptotagmin 4 is a Ca(2+) sensor in the fly but not in the rat, that the Ca(2+)-binding properties of C(2) domains cannot be reliably predicted from sequence analyses, and that proteins clearly identified as orthologs may nevertheless have markedly different functional properties.     

Main structural and stereochemical aspects of the antiherpetic activity of nonahydroxyterphenoyl-containing C-glycosidic ellagitannins

Antiherpetic evaluation of five nonahydroxyterphenoyl-containing C-glycosidic ellagitannins, castalagin (1), vescalagin (2), grandinin (3), roburin B (5), and roburin D (7), was performed in cultured cells against four HSV-1 and HSV-2 strains, two of which were resistant to Acyclovir. All five ellagitannins displayed significant anti-HSV activities against the Acyclovir-resistant mutants, but the monomeric structures 1-3 were more active than the dimers 5 and 7. Vescalagin (2) stands out among the five congeners tested as the most potent and selective inhibitor, with an IC50 value in the subfemtomolar range and a selectivity index 5x10(5) times higher than that of Acyclovir. Molecular modeling was used to provide a rationale for the surprisingly lower activity profile of its epimer castalagin (1). These ellagitannins have promising potential as novel inhibitors in the search for non-nucleoside drugs active against Acyclovir-resistant herpes viruses.