Prevention of electrocardiographic and histopathologic alterations in the murine model of Chagas' disease by preinoculation of an attenuated Trypanosoma cruzi strain

The effects of infection with Trypanosoma cruzi on the electrocardiographic tracings of mice were studied in 4.groups of animals: (1) normal; (2) infected with a pathogenic T. cruzi strain (TS COB); (3) immunized with 3 intraperitoneal inocula of 10(6) attenuated T. cruzi epimastigotes (TCC) and (4) immunized-infected, which sequentially received the treatments of groups 3 and 2. Infection and protection were confirmed by xenodiagnosis and histopathology. Isolated alterations such as extrasystolia, 1st degree atrioventricular block, arrhythmia and ST elevation were observed in normal as well as infected mice. However, tracings taken repeatedly on each mouse over a 293 day period revealed a set of alterations which were more frequently seen in infected (14/22) than in normal (4/27) animals (p = 0.00048). These alterations consisted of supraventricular tachycardia, sinus bradycardia and persisting, first degree AV blocks, often associated to pacemaker changes. Inoculation of attenuated T. cruzi (group 3) did not increase these alterations (2/27 mice) but significantly prevented their development after challenge with the pathogenic strain (1/19 versus 14/22 mice, p = 0.000095). Thus, preimmunization reduced not only parasitemia but also a pathogenic consequence of T. cruzi infection. This evidence is relevant for immunoprevention studies against Chagas' disease.

Histological observations on Montenegro's reaction in man

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.

Diagnosis of Helicobacter pylori: comparison of an urease test, histological visualization of curved bacteria and culture

Helicobacter pylori was investigated in 189 patients for culture, microscopic visualization of campylobacter-like organisms (CLO) and a ten minute urease test. In 136 (72%) the bacteria was isolated, and in 98 of them CLO were histologically detected. Specificity, sensitivity, positive and negative predictive values of microscopic visualization of CLO were: 0.77, 0.73, 0.97 and 0.51, respectively; 98 culture-positive patients were urease test positive. Specificity, sensitivity, positive and negative predictive values of the urease test were: 0.83, 0.72, 0.92 and 0.54, respectively. Comparing the urease test with culture of H. pylori combined with microscopic visualization of CLO, its specificity, sensitivity, positive and negative predictive values were: 0.95, 0.71, 0.98 and 0.48, respectively. Probably, these values are not real, since bacteria different from H. pylori could be misclassified as CLO.

Characterization of the Toxicological Effects of Aminocarb on Rats: Hematological, Biochemical, and Histological Analyses

Aminocarb is a widely applied carbamate insecticide with action of controlling pests such as Lepidoptera and Coleoptera. In this study, subchronic effects on Wistar rats were investigated using hematological, biochemical, and histological techniques. Rats were exposed orally at sublethal levels of 10, 20, or 40 mg/kg body weight (groups A, B, and C, respectively) for 14 d. Hematological results revealed no statistical differences after 1 d of exposure but significant reduction in white blood cells detected after 7 d of exposure in group C, as well as, in all treated groups after 14 d of exposure. Biochemical data showed a decrease of acetylcholinesterase activity in all groups after 1 d of exposure with a return to normal after 7 and 14 d. Significant increase in alkaline phosphatase activity of rats exposed to aminocarb was noted after 7 d of treatment. The levels of triglycerides were also significantly decreased. The present investigation also showed a significant increase in content of serum urea and creatinine in animals from group A (14 d), and from groups B and C (7 and 14 d). Histological results demonstrated hemorrhagic focus on hepatic and renal parenchyma in all exposed groups. Taken together, the attained results were dose dependent and indicated adverse effects of aminocarb on hepatic and renal functions, as well as on immune responsiveness at sublethal tested doses.

Host cell adhesion to Schistosoma mansoni larvae in the peritoneal cavity of naive mice: histological and scanning electron microscopic studies

Cercariae of Schistosoma mansoni inoculated into the peritoneal cavity of naive mice induced host cell adhesion to their surface, but after 90 minutes the number of adherent cells sharply decreased. The cell detachment is progressive and simultaneous to the cercaria-schistosomule transformation. The histological study showed mainly neutrophils in close contact with the larvae. Mononuclear cells and some eosinophils were occasionally seen surrounding the adherent neutrophils. The scanning electron microscopy showed cells displaying twisted microvilli and several microplicae contacting or spreading over the larval surface, and larvae completely surrounded by clusters of cells. These results suggest that the neutrophils recognize molecules on the cercarial surface which induce their spreading

P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection

BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.

Whipple's disease. Report of five cases with different clinical features

Whipple's disease (WD) is a rare systemic disease of infectious etiology which involves the small intestine but can virtually affect any organ. We present here five cases (four males and one female) ranging in age from 20 to 59 years. All patients had intestinal involvement associated or not with clinical manifestations linked to this organ. Vegetation in the tricuspid valve was observed in one patient, suggesting endocarditis caused by Tropheryma whippelii, with disappearance of the echocardiographic alterations after treatment. In one of the male patients the initial clinical manifestation was serologically negative spondylitis, with no diarrhea occurring at any time during follow-up. Ocular involvement associated with intestinal malabsorption and significant weight loss were observed in one case. In the other two cases, diarrhea was the major clinical manifestation. All patients were diagnosed by histological examination of the jejunal mucosa and, when indicated, of extraintestinal tissues by light and electron microscopy. After antibiotic treatment, full remission of symptoms occurred in all cases. A control examination of the intestinal mucosa performed after twelve months of treatment with sulfamethoxazole-trimethoprim revealed the disappearance of T. whippelii in four patients. The remaining patient was lost to follow-up.

Pancreatic involvement in co-infection visceral leishmaniasis and HIV: histological and ultrastructural aspects

The involvement of the gastrointestinal tract in the co-infection of HIV and Leishmania is rarely reported. We report the case of an HIV-infected adult man co-infected with a disseminated form of leishmaniasis involving the liver, lymph nodes, spleen and, as a feature reported for the first time in the English literature, the pancreas. Light microscopy showed amastigote forms of Leishmania in pancreatic macrophages and immunohistochemical staining revealed antigens for Leishmania and also for HIV p24. Microscopic and ultrastructural analysis revealed severe acinar atrophy, decreased zymogen granules in the acinar cytoplasm and also nuclear abnormalities such as pyknosis, hyperchromatism and thickened chromatin. These findings might correspond to the histologic pattern of protein-energy malnutrition in the pancreas as shown in our previous study in pancreas with AIDS and no Leishmania. In this particular case, the protein-energy malnutrition may be due to cirrhosis, or, Leishmania or HIV infection or all mixed. We believe that this case represents the morphologic substratum of the protein energy malnutrition in pancreas induced by the HIV infection. Further studies are needed to elucidate these issues.

Hepatitis C viral load does not predict disease outcome: going beyond numbers

The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV) load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index). Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins), host (sex, age, weight, etc) and treatment variables (dosage, time of treatment, type of interferon) within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV) and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.

Púrpura. Manifestação de Amiloidose Sistémica Primária

Primary Systemic Amyloidosis (AL) is the most frequent form of systemic amyloidosis and its morbilility is associated with immunoglobulin light chains deposition in vital organs. The mucocutaneous manifestations occur in about 30-40% of the cases and are important in diagnostic suspicion, once they appear in early stages of disease. We report a 71-years-old female patient, with disseminated purpura and cutaneous fragility with 6 months of evolution, accompanied by recent complaints of dysphagy. The first laboratory evaluation didn't show any alterations. The histological and immunohistochemical study of subcutaneous abdominal fat and skin biopsy showed lambda type amyloid protein. In the systemic work-up, we highlight a proteinúria > 1g/24h with Bence Jones proteins and the presence of monoclonal immunoglobulin light chain (lambda type) in serum immunoelectrophoresis. With the diagnosis of primary systemic amyloidosis, treatment with prednisolone and melphalan was started.

American trypanosomiasis and electrocardiographic alterations among industrial workers in São Paulo, Brazil

In this article, we evaluate electrocardiographic (ECG) alterations among urban workers from a mechanical-metallurgical industry in São Paulo, Brazil. In a cross-sectional survey carried out in 1980, we found 2.2% positive serological testing for Trypanosoma cruzi infection among 27,081 workers. A comparison between seropositive workers and a random sample of seronegative workers frequency-matched by age and occupation revealed that seropositive workers had a much lower educational level, and that a higher proportion of seropositive workers had ECG abnormalities (42.7%) when compared to those negative for T. cruzi infection (19.8%). The high frequency of ECG abnormalities suggests the need to provide medical assistance to these workers, without any kind of discrimination and to bring in a form of management that would decrease this dangerous risk to the workers and people around them.

Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunction

Background Erectile dysfunction (ED) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED. Oxidative stress-induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. Methods Male Wistar streptozotocin-diabetic rats (and age-matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H2O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal endothelial nitric oxide synthase (eNOS) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and α-smooth muscle actin (α-SMA) and eNOS–α-SMA. Results There was a significant increase in urinary H2O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2O2 production was significantly increased in late diabetes. Reactivity for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. Conclusions The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes-associated ED.

Aerobic Exercise Does Not Predict Brain Derived Neurotrophic Factor And Cortisol Alterations in Depressed Patients

The pathophysiology of depression is related to neurobiological changes that occur in the monoamine system, hypothalamic-pituitary-adrenal axis, neurogenesis system and the neuroimmune system. In recent years, there has been a growing interest in the research of the effects of exercise on brain function, with a special focus on its effects on brainderived neurotrophic factor (BDNF), cortisol and other biomarkers. Thus, the aim of this study is to present a review investigating the acute and chronic effects of aerobic exercise on BDNF and cortisol levels in individuals with depression. It was not possible to establish an interaction between aerobic exercise and concentration of BDNF and cortisol, which may actually be the result of the divergence of methods, such as type of exercises, duration of the sessions, and prescribed intensity and frequency of sessions.

Alterations in lipid transfer to High-Density Lipoprotein (HDL) and activity of paraoxonase-1 in HIV+ patients

HIV+ patients often develop alterations of the plasma lipids that may implicate in development of premature coronary artery disease. High-density lipoprotein (HDL) has an important role in preventing atherogenesis and the aim of this study was to investigate aspects of HDL function in HIV+ patients. HIV+ patients (n = 48) and healthy control subjects (n = 45) of both sexes with similar age were studied. Twenty-five were not being treated with antiretroviral agents, 13 were under reverse transcriptase inhibitor nucleosidic and non-nucleosidic (NRTI+NNRTI) and 10 were under NRTI + protease inhibitors (NRTI+PI) treatment. Paraoxonase 1 (PON1) activity and the transfer of free and esterified cholesterol, tryglicerides and phospholipids from a lipidic nanoemulsion to HDL were analyzed. In comparison with healthy controls, HIV+ patients presented low PON-1 activity and diminished transfer of free cholesterol and tryglicerides. In contrast, phospholipid transfer was increased in those patients, whereas the transfer of cholesteryl esters was unchanged. NRTI+NNRTI increases the transfer of cholesteryl esters and triglycerides but in NRTI+PI there was no difference in respect to non-treated HIV+ patients. HDL from HIV+ patients has smaller antioxidant properties, as shown by lower PON-1 activity, and the transfer of lipids to this lipoprotein fraction is also altered, suggesting that HDL function is defective in those patients.