Effect of exercise on the maternal outcome in pregnancy of spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sexual Precocity of Nellore Bulls that are Offspring of Super Precocious, Precocious and Normal Cows in Extensive Farming Conditions

Contents The objective of this work was to verify that mothers classified as super precocious (M1) and precocious (M2) produce more precocious bulls than females classified as normal (M3). This study included 21186 animals with an average age of 21.29 +/- 1.77months that underwent a breeding soundness evaluation from 1999 to 2008. Of these animals, 2019, 6059 and 13108 were offspring of M1, M2 and M3 females, respectively. In the breeding soundness examination, the animals were classified as sound for reproduction, sound under a natural mating regime, unsound for reproduction and discarded. To compare the averages obtained for each category of mother within the individual breeding soundness classes, a chi-square test with a 5% error probability was used, considering the effects of year and month of birth and farm. For the three classes of mothers (M1, M2 and M3), 67.26, 67.22 and 64.16% of bull calves were considered sound for reproduction and 19.71, 19.46 and 21.90% were considered unsound for reproduction, respectively. There was no difference in the frequency of animals that were sound for reproduction under the natural breeding regime between the three classes of mothers (8.87, 9.31 and 9.19%, respectively). There was a difference between the numbers of precocious and normal females that were discarded, with frequencies of 4.01 and 4.75%, respectively (p<0.05). There were differences in year and month of birth and farm between super precocious and precocious cows in relation to the breeding soundness classification of the animals. It was concluded that the bull offspring of super precocious and precocious cows presented a higher percentage of approval in the breeding soundness examination than the bull offspring of normal cows, demonstrating that the selection for precocity of females has contributed to an increase in the sexual precocity of the herd in relation to the sexual maturity of bulls.

Long term repercussions in the offspring of diabetic rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Increased DNA damage is related to maternal blood glucose levels in the offspring of women with diabetes and mild gestational hyperglycemia

This study aimed at correlating maternal blood glucose levels with DNA damage levels in the offspring of women with diabetes or mild gestational hyperglycemia (MGH). Based on oral glucose tolerance test results and glycemic profiles, 56 pregnant women were allocated into 3 groups: nondiabetes, MGH, and diabetes. The offspring of these women (56 infants) were also evaluated. Maternal peripheral blood and umbilical cord blood samples were collected and processed for biochemical and DNA damage analysis by the comet assay. A positive correlation between maternal blood glucose mean and increased offspring DNA damage levels was observed. Hyperglycemia played a role in offspring DNA damage, but other diabetes-induced complications were also involved. Increased maternal blood glucose levels can lead to increased offspring DNA damage levels. Therefore, the monitoring, control, and treatment of pregnant women with diabetes and MGH are highly important to ensure a risk-free pregnancy and healthy infants.

Heritability Estimate and Genetic Correlations of Reproductive Features in Nellore Bulls, Offspring of Super Precocious, Precocious and Normal Cows Under Extensive Farming Conditions

The present work aimed to estimate heritability and genetic correlations of reproductive features of Nellore bulls, offspring of mothers classified as superprecocious (M1), precocious (M2) and normal (M3). Twenty one thousand hundred and eighty-six animals with average age of 21.29 months were used, evaluated through the breeding soundness evaluation from 1999 to 2008. The breeding soundness features included physical semen evaluation (progressive sperm motility and sperm vigour), semen morphology (major, minor and total sperm defects), scrotal circumference (SC), testicular volume (TV) and SC at 18 months of age (SC18). The components of variance, heritability and genetic correlations for and between the features were estimated simultaneously by restricted maximum likelihood, with the use of the vce software system vs 6. The heritability estimates were high for SC18, SC and TV (0.43, 0.63 and 0.54; 0.45, 0.45 and 0.44; 0.42, 0.45 and 0.41, respectively for the categories of mothers M1, M2 and M3) and low for physical and morphological semen aspects. The genetic correlations between SC18 and SC were high, as well as between these variables with TV. High and positive genetic correlations were recorded among SC18, SC and TV with the physical aspects of the semen, although no favourable association was verified with the morphological aspects, for the three categories of mothers. It can be concluded that the mothers sexual precocity did not affect the heritability of their offspring reproduction features.

Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas

Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequency of these mutations in many subtypes of gliomas, and their association with clinical features of the patients, is poorly understood. Here we analyzed these loci in 363 brain tumors. ATRX is frequently mutated in grade II-III astrocytomas (71%), oligoastrocytomas (68%), and secondary glioblastomas (57%), and ATRX mutations are associated with IDH1 mutations and with an alternative lengthening of telomeres phenotype. CIC and FUBP1 mutations occurred frequently in oligodendrogliomas (46% and 24%, respectively) but rarely in astrocytomas or oligoastrocytomas (<10%). This analysis allowed us to define two highly recurrent genetic signatures in gliomas: IDH1/ATRX (I-A) and IDH1/CIC/FUBP1 (I-CF). Patients with I-CF gliomas had a significantly longer median overall survival (96 months) than patients with I-A gliomas (51 months) and patients with gliomas that did not harbor either signature (13 months). The genetic signatures distinguished clinically distinct groups of oligoastrocytoma patients, which usually present a diagnostic challenge, and were associated with differences in clinical outcome even among individual tumor types. In addition to providing new clues about the genetic alterations underlying gliomas, the results have immediate clinical implications, providing a tripartite genetic signature that can serve as a useful adjunct to conventional glioma classification that may aid in prognosis, treatment selection, and therapeutic trial design.

Treatment of malignant gastroduodenal obstruction with a nitinol self-expanding metal stent: An international prospective multicentre registry

Background: Duodenal stenting has become a broadly accepted first line of treatment for patients with advanced malignant gastroduodenal obstruction as these patients are difficult to treat and are poor surgical candidates. Aims: To document duodenal stent performance for palliative management of malignant gastroduodenal obstruction. Methods: Multicentre, single arm, prospective registry documenting peroral endoscopic duodenal stenting procedures in 202 patients. Results: Technical success achieved in 98% (CI. 95%, 99%) of stent placements. Increase of Gastric Outlet Obstruction Score by at least 1 point compared to baseline was achieved in 91% (CI, 86%, 95%) of patients persisting for a median of 184 days (CI, 109, 266). By day 5 (CI, 4,6) after stent placement, 50% of patients experienced a score increase of at least 1 point. Improvement from 14% of patients at baseline tolerating soft solids or low residue/normal diet to 84% at 15 days, 86% at 30 days, 81% at 90 days, 79% at 180 days, and 70% at 270 days. Complications included stent ingrowth and/or overgrowth (12.4%), transient periprocedural symptoms (3%), bleeding (3%), stent migration (1.5%), and perforation (0.5%). Conclusions: Safety and effectiveness of duodenal stenting for palliation of malignant gastroduodenal obstruction was confirmed in the largest international prospective series to date. (C) 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Is 2-mm Punch Biopsy Useful in the Diagnosis of Malignant Eyelid Tumors?

Purpose: Two-millimeter punch biopsy is a swift and practical diagnostic tool in the outpatient setting. However, few studies have evaluated the efficacy of the method for diagnosis of malignant eyelid tumors. Methods: This was an observational study of patients with suspicion of malignant eyelid tumor attending the Ocular Plastic Surgery Center at Hospital das Clinicas, University of Sao Paulo School of Medicine. Following standard procedures, preoperative biopsies were taken with a 2-mm trephine and surgical excision was performed with safety margins, followed by reconstruction. Anatomopathologic analysis of the surgical specimen was used as gold standard to evaluate the accuracy of diagnosis by punch biopsy. Results: The study included 50 periocular tumors with suspicion of malignancy. The indicators of efficacy in the identification of malignancy by 2-mm punch biopsy were: sensitivity 88%, specificity 100%, positive predictive value 100%, and negative predictive value 64%. Accuracy was 90% for malignancy and 80% for histologic type. The. index of agreement between the diagnostic methods was 0.722 (p < 0.001). Conclusion: A positive result with 2-mm punch biopsy is a safe indication for surgical excision of the tumor, whereas a negative result does not necessarily imply benignity. In cases of high clinical suspicion, a second biopsy should be taken from a different part of the tumor to rule out malignancy. (Ophthal Plast Reconstr Surg 2012;28:282-285)

Genetic mapping of a new heart rate QTL on chromosome 8 of spontaneously hypertensive rats

Abstract Background Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified. Methods An F2 intercross of Spontaneously Hypertensive Rats (SHR) × Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension. Results Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 ± 3 vs. 314 ± 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22–q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes. Conclusion Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation.

[Pathology of malignant lymphomas--clarity instead of confusion]

After decades of confusion in lymphoma classification clearness was achieved with the publication of the REAL classification 1994 and of the WHO classification 2001. The revised 4th edition 2008 features some additional new categories. The WHO classification comprises B- and T-lymphoblastic neoplasms, mature B-cell lymphomas, mature T-cell and NK-cell lymphomas and Hodgkin lymphomas. A modern diagnostic work-up of lymphomas is based on morphology, immunohistochemistry and increasingly on molecular studies. Last but not least the evaluation of all these findings by an expert haematopathologist, who collaborates closely with the treating clinicians, is essential. The aim is to give an overview of the most frequent mature B-cell lymphomas and the most important classical Hodgkin lymphomas with focus on morphology and immunohistochemistry.

Peptide receptor radioligand therapy is an effective treatment for the long-term stabilization of malignant gastrinomas

Gastrinomas, a rare group of neuroendocrine tumors, are responsible for severe peptic disease and diarrhea. Although symptomatic control may be achieved with proton-pump inhibitors (PPIs) and somatostatin analogues (SSAs), data are limited regarding the possible antitumor effect of the peptide receptor radioligand therapy (PRRT) with radiolabeled SSAs in gastrinoma patients. The goal of this study was to assess the effect of PRRT on symptoms, gastrin secretion, and tumor load in patients with progressive malignant gastrinomas.

[Molecular biology of malignant lymphomas for non-specialists]

Lymphomas comprise a variety of entities with remarkable clinical heterogeneity. This review summarizes the current knowledge on the pathogenesis of major mature B-cell lymphoma subtypes for clinicians working outside the field of hemato-oncology. The understanding of the pathogenesis of lymphomas is linked to the knowledge on normal B-cell differentiation. The clinical diversity is manifested in the different mechanisms involved in lymphomagenesis that include characteristic chromosomal translocations deregulating proto-oncogenes, and inactivation of tumor suppressor genes through deletions and mutations. Gene-expression profiling has dissected certain lymphomas into morphologically indistinguishable, but clinically important subgroups and uncovered pathways suitable for specific therapeutic interventions.