Metabolism of ethanol to acetaldehyde by rat uterine horn subcellular fractions

Controversial studies from others suggested that alcohol intake could be associated with some deleterious effects in the uterus. Not all the effects of alcohol drinking on female reproductive organs can be explained in terms of endocrine disturbances. Deleterious effect of alcohol or its metabolites in situ could also play a role. Accordingly, we found a metabolism of alcohol to acetaldehyde in the rat uterine horn tissue cytosolic fraction mediated by xanthine oxidoreductase, requiring a purine cosubstrate and inhibited by allopurinol. This activity was detected by histochemistry in the epithelium and aldehyde dehydrogenase activity was detected in the muscular layer and in the serosa. There was a microsomal process, not requiring NADPH and of enzymatic nature, oxygen-dependent and inhibited by diethyldithiocarbamate, diphenyleneiodonium and partially sensitive to esculetin and nordihydroguaiaretic acid. The presence of metabolic pathways in the uterine horn able to generate acetaldehyde, accompanied by a low capacity to destroy it through aldehyde dehydrogenase, led to acetaldehyde accumulation in the uterus during ethanol exposure. Results suggest that any acetaldehyde produced in situ or arriving to the uterine horn via blood would remain in this organ sufficiently to have the opportunity to react with critical molecules to cause deleterious effects.     

Acute HIV seroconversion presenting with active tuberculosis and associated with high levels of T-regulatory cells

A patient with well-defined acute HIV infection who developed concomitant pulmonary tuberculosis during the retroviral acute syndrome is reported here. In this patient high levels of T-regulatory cells (Tregs) and a low proliferation response to M. tuberculosis were initially detected, which normalized throughout follow-up. This case calls for the consideration of tuberculosis in patients in the early stages of HIV, and emphasizes the need for further study of the potential causal relationship between Treg cells and the risk of TB reactivation in HIV patients.     

Amyotrophic lateral sclerosis,enteral nutrition and the risk of iron overload

Journal of Neurology -     

Comparison of Surgically Resected Polypoid Lesions of the Gallbladder to their Pre-operative Ultrasound Characteristics

Background  Polypoid lesions of the gallbladder (PLG) have been a common finding on ultrasound examinations of the abdomen and are more prevalent since our use of equipment incorporating pulse shaping increased bandwidth, and enhanced phase use for image reconstruction began in 1996. Our study correlates the pre-operative ultrasonographic findings of these lesions to the surgically resected specimen with specific regard to identifying neoplastic polyps. Methods  A retrospective review was performed of 130 patients who had a pre-operative ultrasound of the gallbladder and subsequently underwent cholecystectomy between August 1996 and July 2007 at the Mayo Clinic Rochester. Results  Seventy-nine pseudopolyps (cholesterol polyps, inflammatory polyps, and adenomyomas) and 15 neoplastic polyps were identified on histopathologic analysis. However, 36 patients (27%) did not have a PLG upon histopathologic analysis. Thirty-one polyps had suspicious ultrasonographic characteristics for neoplastic changes. Twenty-nine were ≥10 mm, 12 had vascularity, and one demonstrated invasion. Of these, there were 23 pseudopolyps and six true polyps with neoplastic changes on final pathology (four dysplastic adenomas and two adenocarcinomas). Three asymptomatic polyps ≤10 mm (4%) in maximum diameter based on pre-operative ultrasound imaging (US) had neoplastic changes at pathology (two dysplastic adenomas and one adenocarcinoma). Several statistically significant risk factors were identified that increased the likelihood for malignancy in a PLG: history of primary sclerosing cholangitis (PSC), local invasion, vascularity, and ≥6 mm maximum diameter based on pre-operative US. Of PLGs ≤10 mm, 7.4% were neoplastic. Twenty-five patients were followed up with at least two serial ultrasound examinations. Of these, seven demonstrated polyp growth. None of these specimens demonstrated neoplastic changes. The positive predictive value (PPV) and negative predictive value (NPV) for ultrasound diagnosing neoplastic changes based on current criteria was 28.5% and 93.1%, respectively, with a false negative rate of 5.0%. Expanding the criteria to include cholecystectomy for PLGs ≥ 6 mm changes the positive predictive value and negative predictive value to 18.5% and 100%, respectively, with a false negative rate of 0%. Conclusion  Histopathologic analysis of polypoid lesions of the gallbladder continues to be the gold standard to identify malignancy. Ultrasound has been used extensively in the pre-operative management of these lesions, but modern ultrasound techniques are unable to differentiate between benign and malignant PLGs with any certainty. We recommend that strong consideration be given to surgical resection of PLGs ≥ 6 mm based on pre-operative US due to the significant risk of neoplasm. Additionally, PLGs in all patients with PSC, any patient in whom diligent long-term follow-up cannot be completed, and lesions that demonstrate growth, vascularity, invasion, or are symptomatic require cholecystectomy. Presented at SSAT at the DDW     

Progesterone modulates brain-derived neurotrophic factor and choline acetyltransferase in degenerating Wobbler motoneurons

Progesterone (PROG) shows neuroprotective effects in nervous system diseases. The Wobbler mouse, a model of motoneuron degeneration, suffers a mutation of the Vsp154 gene on chromosome 11 leading to motoneuron vacuolation and astrocytosis of the spinal cord. Previous work has demonstrated beneficial effects of PROG in the Wobbler mouse. As an extension of this work, we now studied steroid effects on neuronal brain-derived neurotrophic factor (BDNF) mRNA and protein, on choline acetyltransferase (ChAT) immunoreactivity (IR) and activity in the spinal cord, and on recovery of muscle atrophy. Wobbler mice received implants of PROG pellets (20 mg) at 6 and 10 weeks of age and were killed at 14 weeks. In situ hybridization for BDNF mRNA demonstrated that grain density in large (>600 microm2) and medium size (<600 microm2) ventral horn neurons was decreased in untreated Wobblers, whereas PROG treatment increased BDNF mRNA in both neuronal types. PROG also induced a subcellular redistribution of BDNF protein, which in controls and steroid-naive Wobblers showed a predominant perinuclear and nucleolar location, whereas after PROG treatment, it was detected in cytoplasmic aggregates. ChAT activity was reduced by 55.3% in muscles of untreated Wobbler mice, whereas a significant increment was obtained after PROG treatment. Wobblers also showed reduced number of ChAT positive motoneurons, but this number was restored to normal by PROG. Finally, the pronounced biceps atrophy of steroid-naive Wobbler mice was slightly but significantly increased by PROG-treatment. Considering the important role played by neurotrophins on neuronal function, changes in BDNF might be part of the PROG activated-pathways to provide neuroprotection and re-establish neurotransmission and neuromuscular function in this degeneration model.     

Cross-talk between CD31 and the signaling lymphocytic activation molecule-associated protein during interferon- gamma production against Mycobacterium tuberculosis

Effective host defense against tuberculosis requires Th1 cytokine responses. We studied the regulation of interferon (IFN)- gamma production during tuberculosis by investigating the role of CD31, a receptor that attenuates T cell receptor signals. After antigen stimulation, CD3(+)CD31(+) blood lymphocytes decreased in healthy donors and in tuberculosis patients with robust Th1 responses to Mycobacterium tuberculosis and IFN- gamma was secreted only by CD31(-) T cells. In contrast, in patients with weak Th1 cytokine responses to M. tuberculosis, the level of CD3(+)CD31(+) lymphocytes was increased and IFN- gamma production was low. Furthermore, the inverse relationship between CD31 expression and IFN- gamma production was in contrast to signaling lymphocytic activation molecule (SLAM) expression, an IFN- gamma inducer in tuberculosis. Interestingly, CD31 bound to SLAM-associated protein (SAP), an IFN- gamma inhibitor in tuberculosis, and when CD31 and SAP were coexpressed in lymphocytes, their association inhibited the IFN- gamma response to M. tuberculosis. Thus, CD31, when binding to SAP, interferes with Th1 responses, suggesting that CD31 has a key regulatory role in the signaling pathway(s) leading to the IFN- gamma response to M. tuberculosis.     

Trypanosoma cruzi Lineages Detected in Congenitally Infected Infants and Triatoma infestans from the Same Disease-Endemic Region under Entomologic Surveillance in Paraguay

Trypanosoma cruzi II is associated with Chagas disease in the southern part of South America. We analyzed T. cruzi variants in field-collected triatomines and congenitally infected infants living in the same disease-endemic region in Paraguay. Results of polymerase chain reactions for T. cruzi kinetoplast DNA and satellite DNA were positive in 83 triatomine feces samples and 58 infant blood samples. However, lineages were detected in 33 and 38 samples, respectively. Trypanosoma cruzi genotypes were determined in 56 (97%) blood samples after hybridization by using specific probes. The Tc I genotype was not detected. The prevalent sublineage was Tc IId in triatomines (27 of 33) and infant blood (36 of 58) as assessed by amplification of the 24Sα ribosomal RNA and the mini-exon region genes. The Tc IIc genotype was detected in 20 infant blood samples and in 1 triatomine. This study shows T. cruzi II is the predominant lineage circulating in triatomines and humans in endemic areas of eastern region of Paraguay.     

Transferability indices for health economic evaluations: methods and applications

In this paper, we have elaborated an index in two phases to measure the degree of transferability of the results of the economic evaluation of health technologies. In the first phase, we have considered the objective factors (critical and non-critical) to derive a general transferability index, which can be used to measure this internal property of the studies of economic evaluation applied to health technologies. In the second phase, with a more specific index, we have measured the degree of applicability of the results of a given study to a different setting. Both indices have been combined (arithmetic and geometric mean) to obtain a global transferability index. We have applied the global index to a sample of 27 Spanish studies on infectious diseases. We have obtained an average value for the index of 0.54, quite far from the maximum theoretical value of 1. We also found that 11 studies lacked some critical factor and were directly deemed as not transferable.