Chronic mercury exposure at different concentrations produces opposed vascular responses in rat aorta

Mercury chloride exposure for 30 days decreases NO bioavailability and increases oxidative stress. However, the mechanisms underlying the effects of mercury on the cardiovascular system are not completely understood, and it is not known if they are dose‐dependent or if some concentrations have no harmful effects. Thus, we investigated the effects of chronic exposure to doses low (half) and high (2.5‐fold higher) than that needed to obtain 29 nmol/L of HgCl₂ on the vascular function. Three‐month‐old male Wistar rats received intramuscular (i.m.) HgCl₂ for 30 days and were divided in three groups: lower (Low Hg); higher (High Hg); and saline was used as the control. High Hg exposure increased the contractile response to phenylephrine (PHE) in aortic rings, but Low Hg reduced it. The hyporesponsiveness in the Low Hg rats was blunted by endothelial denudation and NOS inhibition with l ‐NAME (100 μmol/L). The phosphorylated‐eNOS/eNOS protein ratio increased in the aortas of Low Hg rats. In the High Hg group, endothelial denudation increased the PHE‐induced contractions, while l ‐NAME had no effects and indomethacin (10 μmol/L), losartan (10 μmol/L) and apocynin (30 μmol/L) reduced this response. In the High Hg group, protein levels of the NADPH oxidase subunit gp91phox and cyclooxygenase‐2 increased. Our results support previous suggestions that High Hg increases oxidative stress that might activate an inflammatory cascade and the renin‐angiotensin system. However, very low Hg concentrations below the level considered safe still reduced vascular reactivity, suggesting the need for special attention to continuous exposure as a putative cause of increased cardiovascular risk.     

Sensitivity and specificity of first screen mammography in the Canadian National Breast Screening Study: a preliminary report from five centers

Sensitivity and specificity of first screen mammography in a randomized screening trial at five centers are reported. A total of 23,101 women underwent mammography; in 139, breast cancer was detected at first screening; in 20, less than 12 months after first screening; and in 47, at second screening. All 206 cancer cases were histologically confirmed, and 174 were defined as being detectable at first screening. Average length of follow-up for all women was 3.2 years. Interpretations of first screen mammograms by the center radiologists were matched to known outcomes. Simultaneous blind review was performed by a single reference radiologist with mammograms from all 206 cancer cases and those of a random sample of 739 women not known to have breast cancer at 15 months or more after initial screening. Overall, the five screening centers achieved a sensitivity of 69% (range, 60%-78%), a specificity of 94% (range, 93%-96%), a positive predictive value of 8.6% (range, 3%-16%), and a negative predictive value of 99.7% (range, 99.6%-99.9%).     

Microarray-based identification of thermophilic Campylobacter jejuni,C. coli,C. lari,and C. upsaliensis

DNA microarrays are an excellent potential tool for clinical microbiology, since this technology allows relatively rapid identification and characterization of microbial and viral pathogens. In the present study, an oligonucleotide microarray was developed and used for the analysis of thermophilic Campylobacter spp., the primary food-borne pathogen in the United States. We analyzed four Campylobacter species: Campylobacter jejuni, C. coli, C. lari, and C. upsaliensis. Our assay relies on the PCR amplification of specific regions in five target genes (fur, glyA, cdtABC, ceuB-C, and fliY) as a first step, followed by microarray-based analysis of amplified DNAs. Alleles of two genes, fur and glyA, which are found in all tested thermophilic Campylobacter spp., were used for identification and discrimination among four bacterial species, the ceuB-C gene was used for discrimination between C. jejuni and C. coli, and the fliY and cdt genes were used as additional genetic markers specific either for C. upsaliensis and C. lari or for C. jejuni. The array was developed and validated by using 51 previously characterized Campylobacter isolates. All isolates were unambiguously identified on the basis of hybridization patterns with 72 individual species-specific oligoprobes. Microarray identification of C. jejuni and C. coli was confirmed by PCR amplification of other genes used for identification (hipO and ask). Our results demonstrate that oligonucleotide microarrays are suitable for rapid and accurate simultaneous differentiation among C. jejuni, C. coli, C. lari, and C. upsaliensis.     

Antiproliferative effects of natural interferon beta alone and in combination with natural interferon gamma on human breast carcinomas in nude mice

Summary Nude mice bearing bilateral xenografts of human breast carcinoma cells (MCF-7 and BT20) were treated with 2 or 4 5-day cycles of intralesional (i.l.) injections of human natural interferon beta (nIFN-) alone or in combination with human natural interferon gamma (nIFN-). The injections were administered to only 1 of the 2 tumors in each animal, thus making it possible to assess at the same time local therapeutic effects in the injected tumors and systemic effects in the contralateral ones. When n-IFN- was used as a single agent only mild local antitumor effects and virtually no systemic effects were observed. In contrast, the combined administration of nIFN-/nIFN- produced marked antiproliferative effects, presumably as a result of the synergistic action of type I and type II IFNs. These effects ranged from complete regression documented histologically in 2 MCF-7 tumors to varying degrees of growth inhibition with persistence of residual microscopic or grossly detectable tumor. Local effects were more pronounced than systemic effects. The therapeutic efficacy of nIFN- proved to be greater than that of recombinant interferon beta (rIFN-). In MCF-7 tumors nIFN- appeared to be less effective than nIFN-, whereas the opposite was true for BT 20 tumors.     

Injection of prostaglandin F2alpha into the bronchial artery in sheep increases the pulmonary vascular permeability to protein

Lung injury and oedema following smoke inhalation are associated with eicosanoid release and the injury is heavily influenced by the tracheobronchial circulation. We hypothesized that injection of a vasoactive eicosanoid, prostaglandin F2alpha (PGF2alpha), into the tracheobronchial circulation would induce a permeability leak in that circulation as measured in lung lymph flow and protein content. PGF2alpha when injected into the bronchial artery increased lung lymph flow, protein content and lymph protein flux (protein times flow). The increase in lymph to plasma protein concentration after injection of PGF2alpha is consistent with an increase in vascular protein permeability since an increase in pressure alone would cause an increase in fluid flow in excess of protein with a fall in protein concentration. Ligation of the bronchial artery 3min after injection of the PGF2alpha largely prevented the late changes suggesting that the protein leak into the lymph was from the bronchial arteries.     

Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome

Chonchaiya W, Nguyen DV, Au J, Campos L, Berry‐Kravis EM, Lohse K, Mu Y, Utari A, Hervey C, Wang L, Sorensen P, Cook K, Gane L, Tassone F, Hagerman RJ. Clinical involvement in daughters of men with fragile X‐associated tremor ataxia syndrome. Women with the fragile X mental retardation 1 (FMR1) premutation often have concerns about neurological and medical problems, as they become older and if their fathers experience fragile X‐associated tremor/ataxia syndrome (FXTAS). We therefore determined the prevalence of these problems in 110 daughters of men with FXTAS [mean age of 44.8 years (SD 8.2)]. We compared them with 43 female controls with normal FMR1 alleles [mean age of 43.8 years (SD 8.1)] and 36 premutation carrier daughters of parents with the premutation, but without FXTAS [mean age of 43.5 years (SD 7.7)]. Overall, daughters of men with FXTAS have a higher prevalence of neurological symptoms including tremor, balance problems, memory problems, and dizziness, menopausal symptoms, and psychiatric involvement including sleep problems and anxiety when compared with non‐carrier female controls. Reported balance problems and menopausal symptoms were significantly higher in daughters of men with FXTAS than in carrier daughters of parents without FXTAS, suggesting the potential influence of background gene effects. Therefore, neurological, psychological and gynecological surveillance should be warranted to better provide appropriate counseling, management and care for daughters of men with FXTAS. Biological markers of additional gene effects that predispose individuals with the premutation to FXTAS need to be developed.