Chronic Chagas disease: from basics to laboratory medicine

Chagas disease, caused by Trypanosoma cruzi infection, is ranked as the most serious parasitic disease in Latin America and has huge potential to become a worldwide problem, due to increasing migration, and international tourism, as well as infectant transfer by blood contact and transfusion, intrauterine transfer, and organ transplantation. Nearly 30% of chronically-infected patients become symptomatic, often with a latency of 10-30 years, developing life-threatening complications. Of those, nearly 90% develop Chagas heart disease, while the others manifest gastrointestinal disease and neuronal disorders. Besides interrupting the infection cycle and chemotherapeutic infectant elimination, starting therapy early in symptomatic patients is important for counteracting the disease. This would be essentially supported by optimized patient management, involving risk assessment, early diagnosis and monitoring of the disease and its treatment. From economic and logistic viewpoints, the tools of laboratory medicine should be especially able to guarantee this. After summarizing the basics of chronic Chagas disease, such as the epidemiological data, the pathogenetic mechanisms thought to drive symptomatic Chagas disease and also treatment options, we present tools of laboratory medicine that address patient diagnosis, risk assessment for becoming symptomatic and guidance, focusing on autoantibody estimation for risk assessment and heart marker measurement for patient guidance. In addition, increases in levels of inflammation and oxidative stress markers in chronic Chagas disease are discussed

Assessment of economic factors affecting the satellite power system. Volume 2: The systems implications of rectenna siting issues

The feasibility was evaluated of finding potential sites for Solar Power Satellite (SPS) receiving antennas (rectennas) in the continental United States, in sufficient numbers to permit the SPS to make a major contribution to U.S. generating facilities, and to give statistical validity to an assessment of the characteristics of such sites and their implications for the design of the SPS system. It is found that the cost-optimum power output of the SPS does not depend on the particular value assigned to the cost per unit area of a rectenna and its site, as long as it is independent of rectenna area. Many characteristics of the sites chosen affect the optimum design of the rectenna itself

Rodenticide residues in non-target small mammal species and their occurrence in owl pellets

OBJECTIVES: Distinguishing the patterns of autoantibodies (AAB) against G-protein-coupled receptors in Chagas' cardiomyopathy and megacolon and the discovery of such a pattern in patients who are as yet asymptomatic could help to identify patients at high risk of developing the life-threatening complications of Chagas' disease. BACKGROUND: Such AAB against receptors as beta 1 (beta1-AAB), beta 2 (beta2-AAB), and muscarinergic 2 (M2-AAB) are thought to be involved in the pathogenesis of Chagas' cardiomyopathy and megacolon, the predominant manifestations of Chagas' disease, which is the most serious parasitic disease in Latin America. METHODS: Beta1-AAB, beta2-AAB, and M2-AAB were measured in the serum of asymptomatic Chagas' patients and in those with cardiomyopathy and/or megacolon. RESULTS: Nearly all Chagas' patients with cardiomyopathy and/or megacolon had AAB. Predominance of beta1-AAB combined with M2-AAB in Chagas' cardiomyopathy and beta2-AAB with M2-AAB in megacolon was found. Such patterns were also found in 34% of the asymptomatic patients, of whom 85% possessed a beta1-AAB level typical for Chagas' cardiomyopathy. CONCLUSIONS: The percentage of asymptomatic Chagas' patients who had a specific AAB pattern and had a beta1-AAB level above a defined cutoff point mirrors very well the epidemiological situation, which showed that clinical manifestations develop in nearly 30% of Chagas' patients and cardiomyopathy in nearly 90% of them. We hypothesize that beta1-, beta2-, and M2-AAB measurement might be a useful tool for risk assessment in the indeterminate state of Chagas' disease to select patients for earlier involvement in care programs. However, prospective studies are needed to further evaluate this hypothesis

The duplication of the rectum: presentation and therapy

Aim: to delineate the symptomatic features and to emphasize the necessity of early diagnosis and complete surgical excision of rectal duplications. Method. We undertook a retrospective and contemporary review of all patients. Clinical recordings, preoperative evaluations, intraoperative and histological findings, and current patients’ condition were studied. Results. Age of the six patients ranged from new-born to 13 years. There was a broad spectrum of clinical presentation: two children were seen after previous therapy elsewhere with a mistaken diagnosis of perianal fistula, respectively undefined abdominal pain; two presented with exstrophic duplication of the rectum; one neonate was seen with an anal cleft and one infant with rectal bleeding and retrorectal palpable tumour. Paraclinical investigations established preoperative diagnosis in one patient, aided it in two others, and detected associated anomalies in two further patients. All duplications were “in toto“ removed using laparotomy (n = 1), transanal (n = 1), or perineal sagittal approach(n = 4). All duplications had contact with the rectum. Smooth muscle coat and intestinal epithelial layer were histological demonstrated in each case. Conclusions. Rectal duplications are rare anomalies. Clinical manifestations may include abdominal pain, obstipation, rectal bleeding, urinary or bowel obstruction, rectal polyp, perianal fistula, perineal abscess, and pelvic, abdominal, retroperitoneal or perineal mass. Early diagnosis avoids prolonged symptomatic treatment and unnecessary operative procedures. Complete excision is curative

Does contrast echocardiography induce increases in markers of myocardial necrosis, inflammation and oxidative stress suggesting myocardial injury?

BACKGROUND: Contrast echocardiography is a precise tool for the non-invasive assessment of myocardial function and perfusion. Side effects of contrast echocardiography resulting from contrast-agent induced myocardial micro-lesions have been found in animals. The goal of this study is to measure markers of myocardial necrosis, inflammation and oxidative stress in humans to evaluate potential side-effects of contrast echocardiography. METHODS: 20 patients who underwent contrast echocardiography with Optison as the contrast medium were investigated. To evaluate myocardial micro-necrosis, inflammation and oxidative stress, cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, -8 and thiobarbituric acid reactive substances (TBARS) were measured at baseline and at 2, 4, 8 and 24 hours after contrast echocardiography. RESULTS: At baseline, 50% of the patients had cTnI and TBARS values outside the reference range. TNF-α, IL-6, IL-8 levels were within the reference range. Patients with cTnI above the RR clustered to significantly higher levels of TNF-α and IL-6. After contrast echocardiography, no statistically significant increase of cTnI, cytokines and TBARS was found. However, for nearly 50% of the patients, the intra-individual cTnI kinetics crossed the critical difference (threefold of methodical variation) which indicates a marker increase. This was neither predicted by the baseline levels of the cytokines nor the markers of oxidative stress. CONCLUSION: There are no clinically relevant increases in serum markers for micro-necrosis, inflammation and oxidative stress in humans after contrast echocardiography. Future studies have to address whether cTnI increase in some patients represent a subset with increased risk for side effects after contrast echocardiography

A large scale survey reveals that chromosomal copy-number alterations significantly affect gene modules involved in cancer initiation and progression

Background Recent observations point towards the existence of a large number of neighborhoods composed of functionally-related gene modules that lie together in the genome. This local component in the distribution of the functionality across chromosomes is probably affecting the own chromosomal architecture by limiting the possibilities in which genes can be arranged and distributed across the genome. As a direct consequence of this fact it is therefore presumable that diseases such as cancer, harboring DNA copy number alterations (CNAs), will have a symptomatology strongly dependent on modules of functionally-related genes rather than on a unique "important" gene. Methods We carried out a systematic analysis of more than 140,000 observations of CNAs in cancers and searched by enrichments in gene functional modules associated to high frequencies of loss or gains. Results The analysis of CNAs in cancers clearly demonstrates the existence of a significant pattern of loss of gene modules functionally related to cancer initiation and progression along with the amplification of modules of genes related to unspecific defense against xenobiotics (probably chemotherapeutical agents). With the extension of this analysis to an Array-CGH dataset (glioblastomas) from The Cancer Genome Atlas we demonstrate the validity of this approach to investigate the functional impact of CNAs. Conclusions The presented results indicate promising clinical and therapeutic implications. Our findings also directly point out to the necessity of adopting a function-centric, rather a gene-centric, view in the understanding of phenotypes or diseases harboring CNAs.Spanish Ministry of Science and Innovation (grant BIO2008-04212)Spanish Ministry of Science and Innovation (grant FIS PI 08/0440)GVA-FEDER (PROMETEO/2010/001)Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grant RD06/0020/1019)Instituto de Salud Carlos III (ISCIII)Spanish Ministry of Science and InnovationSpanish Ministry of Health (FI06/00027

Increasing Protein at the Expense of Carbohydrate in the Diet Down-Regulates Glucose Utilization as Glucose Sparing Effect in Rats

High protein (HP) diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP) on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein) for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein) for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD). Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1st day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets