Mutational specificity of aflatoxin B1. Comparison of in vivo host-mediated assay with in vitro S9 metabolic activation

An intrasanguineous host-mediated assay was used to determinethe pattern of mutagenesis induced by the carcinogen aflatoxinBl in the lacl gene of Escherichia coli recovered from rat liver.To investigate the influence of different types of metabolicactivation, the mutation spectrum induced by AFB1 activatedin vitro by a commercially prepared S9 microsomal fraction fromAroclor 1254-treated rats was also obtained. A total of 281forward mutations affecting the N-terminal region of the laclgene were characterized by DNA sequencing analysis. AFB1 inducedsimilar type of mutations with similar site specificity whenactivated by the standard S9 fraction or by employing a rathost-mediated assay. These results indicate the ability of thein vitro S9 fraction to mimic the in vivo metabolism, suggestingthat the same active metabolite, presumably AFB1 8, 9-epoxide,is responsible for generating a similar pattern of DNA damage,as reflected in the similarity of mutational spectra. For bothactivation systems, most mutations (>90%) were base substitutionsthat occurred primarily at G: C pairs. Somewhat over one-halfof G: C targeted substitutions were GC>TA transversions,other mutations being evenly divided between G: C>AT transitionsand GC>CG trans-versions. The mutational specificity exhibitedby activated AFB1 can be explained by incorporation of differentbases opposite a single type of non-instructive lesion duringerror-prone DNA synthesis. To what extent the mutations aredue to the main adduct (AFB1-N7-Gua), its imidazole-ring-openedderivative or an apurinic site remains unknown.     

Comparative assessment of bone mineral density of the forearm using single photon and dual X-ray absorptiometry

Summary Forearm bone mineral density (BMD) was measured at proximal and distal sites by ¹²⁵I single photon absorptiometry (SPA) and by dual energy X-ray absorptiometry (DXA) in 67 consecutive subjects, aged 18–75 years. Correlations and regression equations between these two techniques were determined. All forearm measurements were significantly correlated with each other (r=0.599–0.926; P0.0001). Although SPA and DXA correct for fat in different ways, we found similar correlation and regression equations in women with body mass index measurements above and below the mean. In addition, forearm measurements by both techniques were moderately correlated with vertebral spine and hip BMD. We conclude that overall, SPA forearm measurements in a population can be calibrated to DXA measurements if necessary, and that DXA forearm measurements are as predictive of the remainder of the skeleton as SPA measurements.     

Aristolochic acids in Aristolochia chilensis

The major components of the acid fraction of the leaves and tender stems of Aristolochia chilensis Miers are aristolochic acids I and Ia. Aristolochic acid Ia has been isolated from plant material for the f?rst time, and its PMR spectrum is discussed.     

Factores pronósticos del cáncer de mama. Modelo predictivo

Introduction. Breast cancer remains the most frecuent tumor among women in developed countries. The prognosis is linked to a great variety clinic and pathological factors. The objectives from this study are to identify markers related to survival of patients with primary diagnosis of breast cancer. Material and methods. We have reviewed the medical dossier from 2.227 consecutive women diagnosed for infiltrating breast cancer between January 1966 and december 2000 in a single institution. For statistic analysis we used 10.0 SPSS software. Results. In the univariate analysis, factors with the strongest predictive value for overall survival were: PEV, estrogene and progesterone receptors, TNM stage, lymphatic vessel involvement, histologic grade, Scarff differentiation and mitosis rate, elastosis, presence of histiocitosis, and the percentage of involved stage I and III lymph nodes (Berg clasification). In the multivariate analysis, 5 factors; progesterone receptors, Scarff mitotic rate, lymphatic vessel involvement, percentage of involved stage I lymph nodes, and presence of metastasis; were independent prognostic markers of survival. Conclusions. Many independent factors interact in the survival of patients with primary breast cancer. Determination of hormonal receptors, mainly progesterone’s, appear as the most powerful indicators. The analysis has generated a prognostic simplified classification, based in the 5 independent variables, that provides specific rates for survival at 2, 5 and 10 years.     

Pain and Bradykinin Receptors--sensory transduction mechanism in the nociceptor terminals and expression change of bradykinin receptors in inflamed condition]

Bradykinin (BK), an endogenous algesic and sensitizing substance, excited nociceptors and sensitized their heat responses. These effects were mediated by B2 receptors (B2Rs) in normal condition, and B1 receptors were additionally recruited in inflammation. B2Rs were coupled with Gq/11 and their activation resulted in diacylglycerol and inositol triphosphate release. Diacylglycerol activated protein kinase (PK) Cepsilon in sensory neurons. To clarify what channel was modulated by PKC to depolarize nociceptor terminals, we examined the heat activation threshold (Tt) of heat-sensitive capsaicin receptor (TRPV1). Tt was lowered down to 31 degrees C by BK in concentration dependent manner through activation of PKCepsilon in cells heterologously expressing TRPV1 and B2Rs. Thus both excitation and sensitization to heat could be explained by one mechanism, lowering Tt of TRPV1. The same was observed in capsaicin-sensitive primary sensory neurons. However, TRPV1 knockout mice showed almost no change in BK-induced nociceptive behavior and nociceptor excitation, although BK-induced heat hyperalgesia completely disappeared, suggesting that TRPV1 was not the sole channel that was modulated by BK to depolarize nociceptor terminals. In addition nociceptor sensitivity to BK was augmented in inflamed animals, with B2R mRNA and protein upregulated. The mechanism for prostaglandin-induced augmentation of BK response is left open for future study.     

Non beating heart donors as a possible source for liver transplantation

Organ shortage for liver transplantation continues to be a major problem. Non heart beating donors (NHBD) are gaining increasing importance as a potential source of transplantable organs for clinical use, mainly in kidney transplantation. Up to now, the experience in liver transplantation with this type of donors has been limited and has only been considered in donors in whom cardiac arrest (CA) has occurred at a known given time. This is due to the high risk of primary non-function and late complications related to intrahepatic biliary lesions when warm ischemia time (WIT) is not controlled. The method of retrieval of these organs should offer the possibility to stop liver injury, revert histologic lesions appeared after WIT, and to assess the quality of the potential donor liver. Based on the experience of kidney transplantation, total body cooling achieved by extracorporal cardiopulmonary bypass seems to be the best method. Moreover it allows the inclusion of a time for tissue oxygenation at 37 degrees C (Normothermic Recirculation, NR) prior to body cooling which has been shown to improve graft viability, and also allows a time to measure organ quality before transplantation. In our experience, we demonstrated that liver transplantation from NHBD is feasible; NR has beneficial effect on liver viability improving endothelial cell damage, hepatocyte energy charge and histological changes at 5 days. We also showed that time of cardiac arrest is determinant of graft viability; even if hepatocellular function is preserved after 40 minutes of CA using NR, irreversible intrahepatic biliary lesions are always present and burden long-term survival. Moreover, bypass pump and blood flows are directly related to WIT and the achievement of better pump flows may predict survival during NR. In animals with 40 minutes of CA, we also reported the possibility to manipulate the potential graft during NR with L-Arginine, Glycine and S-Adenosyl-Methyonine, which minimize endothelial and hepatocellular damage as well as lesions at 5 days. Further research needs to be done in order to confirm our experimental data.     

Hérida Regina Nunes SALGADO,et al:Microbiological assay for the determination of azithromycin in ophthalmic solutionsMicrobiological assay for the determination of azithromycin in ophthalmic solutions

IntroductionAzithromyciniscommercializedbypharmaciesinBrazilinophthalmicsolutionform. Despitetheproveneffectivenessandsafetyinitstreatment, thisdrug,untilthen, doesnotpossessamethodologyofstandar dizedanalysisforophthalmicsolutionsinofficialcom pendiumsan…     

Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney

It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole.     

Evisceración transvaginal post-histerectomía radical y radioterapia adyuvante

Transvaginal evisceration is a rare situation, with few cases reported in the international literature. This situation normally occurs in postmenopausal women and is associated with previous vaginal surgery, especially hysterectomy. The defect in the vaginal fundus requires emergency surgery, and even resection of the affected section of the bowel, if necessary. We report a case of vaginal evisceration of the small bowel 14 years after radical hysterectomy in a patient with endometrial cancer and vaginal vault prolapse.