[D-Leu1]MC-LR Has Lower PP1 Inhibitory Capability and Greater Toxic Potency than MC-LR in Animal and Plant Tissues.

Two microcystins, MC-LR and [D-Leu1]MC-LR, present in La Plata Basin blooms, are differentiated by substitution of D-Alanine for D-Leucine at position 1. Our objective was to evaluate acute toxicity of [D-Leu1]MC-LR and MC-LR in mice (N:NIH Swiss) and beans (Phaseolus vulgaris). We observed variations in [D-Leu1]MC-LR lethal doses with respect to those reported for MC-LR (100 µg/kg), with an increased liver/body weight ratio and intrahepatic hemorrhages in mice exposed to 50-200 µg [D-Leu1]MC-LR/kg and slight steatosis after a single 25 µg [D-Leu1]MC-LR/kg i.p. dose. Our study in the plant model showed alterations in germination, development, morphology and TBARs levels after a single contact with the toxins during imbibition (3.5 and 15 µg/mL), those treated with [D-Leu1]MC-LR being more affected than those treated with the same concentration of MC-LR. Protein phosphatase 1 (PP1) IC50 values were 40.6 nM and 5.3 nM for [D-Leu1]MC-LR and MC-LR, respectively. However, the total phosphatase activity test in root homogenate showed 60% inhibition for [D-Leu1]MC-LR and 12% for MC-LR. In mouse liver homogenate, 50% inhibition was observed for [D-Leu1]MC-LR and 40% for MC-LR. Our findings indicate the need for further research into [D-Leu1]MC-LR toxicity since together with oxidative stress, the possible inhibition of other phosphatases could explain the differences detected in the potency of the two toxins.

Analysis association between mitochondrial genome instability and xenobiotic metabolizing genes in human breast cancer.

The aim of this study was to determine the existence of association between the genetic polymorphisms of metabolizing genes GSTM-1, GSTT-1, and NAT-2, and the presence of mitochondrial genome instability (mtGI) in breast cancer cases. Ninety-four pairs of tumoral/nontumoral breast cancer samples were analyzed. Our samples showed 40.42% of mtGI by analysis of two D-loop region markers, a (CA)n mtMS starting at the 514-bp position, and four informative MnlI sites between the 16,108-16,420-bp. GSTM-1 null genotype has shown a significant association with mtGI presence (chi(2) = 7.62; P = 0.006) in breast cancer cases; moreover, these genotypes also are related to an increased risk for mtDNA damage (odds ratio [OR] = 3.71 [1.41-9.88]; 95% Cornfield confidence interval [CI]). These results suggest that the absence of GSTM-1 enzymatic activity favors chemical actions in damaging the mtDNA. Analysis of GSTT-1 and NAT-2 polymorphisms showed no association with mtGI (chi(2) = 0.03; P = 0.87 and chi(2) = 2.76; P = 0.09, respectively). The analysis of invasive breast cancer cases showed mtGI in 74.36% of ILC cases (29 of 39 samples), and in only 18.75% (9 out of 48) IDC cases; this result suggests a possible relation between mtDNA mutations and variations in molecular pathways of tumor development.

Hepatic and intestine alterations in mice after prolonged exposure to low oral doses of Microcystin-LR.

Oral intake of Microcystin-LR (MC-LR) is the principal route of exposure to this toxin, with prolonged exposure leading to liver damage of unspecific symptomatology. The aim of the present paper was therefore to investigate the liver and intestine damage generated by prolonged oral exposure to low MC-LR doses (50 and 100 µg MC-LR/kg body weight, administrated every 48 h during a month) in a murine model. We found alterations in TBARS, SOD activity and glutathione content in liver and intestine of mice exposed to both doses of MC-LR. Furthermore, the presence of MC-LR was detected in both organs. We also found hepatic steatosis (3.6 ± 0.6% and 15.3 ± 1.6%) and a decrease in intraepithelial lymphocytes (28.7 ± 5.0% and 44.2 ± 8.7%) in intestine of 50- and 100-µg MC-LR/kg treated animals, respectively. This result could have important implications for mucosal immunity, since intraepithelial lymphocytes are the principal effectors of this system. Our results indicate that prolonged oral exposure at 50 µg MC-LR/kg every 48 h generates significant damage not only in liver but also in intestine. This finding calls for a re-appraisal of the currently accepted NOAEL (No Observed Adverse Effect Level), 40 µg MC-LR/kg body weight, used to derive the guideline value for MC-LR in drinking water.

The p53 codon 72 genotypes in HPV infection and cervical disease.

OBJECTIVE: [corrected] An experimental study has indicated that individuals homozygous for the Arg-encoding allele of p53 gene may have an increased susceptibility to HPV-related cervical cancer but many epidemiological studies have failed to repeat this result. Many epidemiological studies have failed in the attempt to repeat this results. The aim of the present work was to investigate whether the p53 arginine allele confers a risk factor for cervical carcinogenesis. STUDY DESIGN: Using PCR based technology, DNAs from 90 normal cervical samples and 205 abnormal cervical tissue scrapes were analyzed for the type of HPV present and p53 codon 72 polymorphism. RESULTS: Non statistically significant differences were found for the frequencies of p53 genotypes in the different cytological/histological groups (chi2=1.4; P=0.97) nor for the risk for HPV infection (chi2=1; P=0.9). CONCLUSION: This study showed that polymorphism at codon 72 of TP53 gene is not associated with an increased susceptibility to cervical disease and/or HPV infection in the Argentine women population.

Diferenciar la apendicitis con o sin fecalito ¿puede cambiar el enfoqueterapéutico?: Resultados preliminares / Differentiating between appendicitis with or without fecalith to change the therapeutic approach: Preliminary results

Antecedentes: el manejo de los pacientes con apendicitis aguda fue clásicamente quirúrgico. En la era de los antibióticos se plantean nuevos paradigmas terapéuticos. La diferencia en el origen de la apendicitis podría establecer el tratamiento por elegir. Objetivo: analizar si la presencia de fecalito en una apendicitis puede condicionar un tratamiento quirúrgico o solo con antibióticos. Material y métodos: análisis descriptivo observacional de las diferencias intraoperatorias y anatomopatológicas de los pacientes operados por apendicitis aguda, divididos en 2 grupos según presentaran fecalito o hiperplasia linfoidea como causa de origen. Se utilizó la prueba de Chi2 para la comparación de ambos grupos, tomando un valor de p<0,05. Resultados: el grupo de apendicitis por fecalito presentó un estadio más avanzado de la enfermedad, con líquido libre con más frecuencia (el 67% de los pacientes con apendicitis aguda por fecalito vs. el 18% en el grupo de apendicitis aguda por hiperplasia), en más de una localización (solo el grupo con fecalito presentó líquido en el fondo de saco de Douglas o en el resto del abdomen, en el 50% y 16,7% respectivamente), con características que variaron entre seroso y purulento y anatomopatológicamente presentaron mayor afectación de las capas histológicas (en el grupo hiperplasia la afectación hasta la mucosa fue 63,6% vs. 16,7%, mientras que en el grupo fecalito fue más frecuente la afectación hasta la serosa 66,6% vs. 27,3%). Conclusiones: los pacientes con apendicitis aguda por hiperplasia linfoidea tendrían menos complicaciones intraabdominales en el posoperatorio y podrían ser buenos candidatos a tratamiento médico solo con antibióticos, evitando la cirugía.

Background: Surgery is the traditional approach for patients with acute appendicitis. In the antibiotic era, new therapeutic paradigms are being proposed. The difference in the cause of appendicitis could establish the treatment of choice. Objective: to analyze if the presence of fecalith in an appendicitis can condition a surgical treatment or only with antibiotics. Material and methods: This observational analysis describes the intraoperative and pathological differences between patients undergoing surgery for acute appendicitis, divided into two groups according to the presence of fecalith or lymphoid hyperplasia as cause of the condition. The chi square test was used to compare the fecalith group versus the lymphoid hyperplasia group using a p value < 0.05. Results: The presence of fecaliths was more commonly associated with advanced stage of inflammation, presence of free peritoneal fluid (67% vs. 18% in the lymphoid hyperlasia group) and in more than one site (50% in the Douglas' pouch and 16.7% in the rest of the abdominal cavity). In this group, peritoneal fluid varied between serous and purulent and more appendiceal layers were involved (63.6% of mucous layer involvement in the lymphoid hyperplasia group vs. 16.7%, while serous compromise was more common in the fecalith group: 66.6% vs. 27.3%). Conclusions: Patients with acute appendicitis due to lymphoid hyperplasia could have lower rate of post-operative complications or could be good candidates for medical treatment with antibiotics alone, avoiding surgery.

Are mammography and palpation sufficient for breast cancer screening? A dissenting opinion.

Breast cancer is an equal opportunity killer in that as many as 60%-70% of breast cancer patients have no obvious risk factor(s). Thus, the continued reliance on the importance of risk factors to initiate screening programs may inhibit further inquiry into better diagnostic and prognostic indicators. An extensive review of past and recent literature reveals that mammography is not an objective examination. Its use as a screening tool is facilitated among women 40 years old and older whose breast tissue is primarily fatty and provides better visualization. Younger women are not generally advised to use mammography because of its potentially hazardous effects associated with repeated use of radiation. More importantly, regardless of patient age, radiologists interpret mammograms, and different degrees of interpretation error exist for different radiologists as well as for the same radiologist performing the analysis after a period of time. Thus, the use of mammography as the sole screening tool does not provide patients or physicians with a sense of confidence about sensitivity and specificity. Further, recent enthusiasm to promote mammography screening may give women unrealistic expectations, leading them to falsely believe that a negative examination is assurance that cancer is not present in its earliest detectable stage. We propose to supplement the physical examination and mammography with a third screening modality based on thermal detection monitors. This is a noninvasive and nonradiogenic tool and might enable clinicians to provide patients with every opportunity for early diagnosis.

Alteraciones histológicas de la mucosa gástrica ante el estres quirúrgico / Histologic alterations of the gastric mucosa in surgical stress

Los autores presentan sus hallazgos en 31 pacientes sometidos a biopsia de mucosa gástrica en el pre postoperatorio con la cápsula de González. Relatan las alteraciones histológicas caracterizadas por edema, gastritis, hemorragia y necrosis. Sobre 93 biopsias postoperatorias hallaron 69 gastritis, 64 de ellas crónicas; 4 crónicas a células plasmáticas y 1 gastritis aguda. Todas fueron de aparición temprana