Insulinoma with peripheral neuropathy: a case report.

BACKGROUND: Insulinomas are rare neuroendocrine tumors that typically present with hypoglycemic crises. Peripheral neuropathy is an uncommon complication of insulinoma. Most clinicians expect peripheral neuropathy symptoms to reverse completely after the insulin-secreting tumor is resected, but this may be a misassumption. CASE REPORT: We report a case of a 16-year-old Brazilian boy with clonic muscle spasms of the lower limbs for almost one year. Disabling paraparesis and confusional episodes had progressively set in as well. There were no sensorial abnormalities in the lower limbs, upper limbs or cranial nerves. An electromyography revealed a motor neuropathy of the lower limbs. The diagnosis of insulinoma was established as serum insulin and C-peptide concentrations were inappropriately normal during spontaneous episodes of hypoglycemia. Following a normal abdominal magnetic resonance scan, the imaging work-up continued with an endoscopic ultrasound, which localized the tumor at the pancreatic body-tail transition. Once localized, a prompt surgical removal (enucleation) of the tumor was undertaken, leading to an immediate and complete resolution of hypoglycemia. The time length between the onset of symptoms and tumor resection was 15 months. After surgery, the symptoms of peripheral neuropathy of the lower limbs showed a slow and only partial improvement. At a two-year follow-up after surgery, although being able to lead a normal and productive life, the patient still reported symptoms of reduced muscular strength in the lower limbs and a new electroneuromyography analysis showed chronic denervation and reinnervation in the legs' muscles-indicating chronic neuropathic injury. CONCLUSION: The events of this case reinforce the importance of an agile diagnostic work-up and spry definitive treatment for patients with this uncommon disease, enabling the cure of neuroglycopenia before permanent bothersome complications ensue.

Corpus callosum size, hypnotic susceptibility and empathy in women with alleged mediumship: a controlled study.

AIM: Evidence indicates that highly hypnotizable subjects may have larger area of the rostrum of the corpus callosum (CC). Mediumship can be defined as the alleged ability to communicate regularly with deceased personalities, and self-hypnosis is postulated as an underlying mechanism for this ability. Therefore, we aimed to investigate the CC area, hypnotic susceptibility, self-reported dissociation, and empathy in alleged mediums in comparison with healthy, non-medium controls. METHODS: The study sample consisted of 16 Spiritist mediums (medium group (MG)) and 16 non-medium controls. Magnetic resonance imaging scans were performed to measure the CC areas (total and subdivisions). The Harvard Group Scale of Hypnotic Susceptibility was used to assess hypnotizability, and self-reported measures were used to investigate anomalous experiences, mental health using the Self-Reporting Questionnaire-SRQ, dissociative experiences using the Dissociative Experiences Scale, and empathy using the Interpersonal Reactivity Index. RESULTS: No between-group differences were found in the total or subdivided CC areas or in hypnotizability, with both groups showing intermediate levels. The rostrum of the CC area and hypnotizability were not correlated. The MG presented with significantly more anomalous experiences, but the two groups had similar scores for dissociation, empathy, and mental health. CONCLUSION: The normal CC areas found in the MG are in contrast with the abnormal results typically observed in subjects with psychotic and dissociative disorders. Although hypnotizability was not different between groups, further studies are needed to replicate these findings in other samples.

"Seat of the soul"? The structure and function of the pineal gland in women with alleged spirit possession-Results of two experimental studies.

BACKGROUND: Cultural traditions attribute to pineal gland an important role for spiritual experiences. Mediumship and spirit possession are cultural phenomena found worldwide which have been described as having dissociative and psychotic-like characteristics, but with nonpathological aspects. A sympathetic activation pattern in response to spirit possession has been reported in some studies, but empirical data on pineal gland is scarce in this context. METHODS: We aimed to investigate pineal gland and pituitary volumes, as well as urinary 6-sulfatoxymelatonin levels in 16 alleged mediums (Medium Group-MG) compared with 16 healthy nonmedium controls (Control Group) (Experiment 1). Furthermore, we aimed to evaluate urinary 6-sulfatoxymelatonin and stress reactivity in GM (n = 10) under different physiological conditions (Experiment 2). RESULTS: In Experiment 1, MG presented higher scores of anomalous experiences, but there were no between-group differences regarding mental health or subjective sleep quality. Similar pineal gland and pituitary volumes were observed between groups. There were no between-group differences in urinary 6-sulfatoxymelatonin collected under equivalent baseline conditions. In Experiment 2, the rise of anxiety and heart rate in response to mediumistic experience was intermediate between a nonstressful control task (reading) and a stressful control task (Trier Social Stress Test-TSST). No significant differences were observed in 6-sulfatoxymelatonin urinary levels between the three conditions. The pattern of stress reactivity during the TSST was normal, but with an attenuated salivary cortisol response. CONCLUSION: The normal neuroimaging and stress reactivity findings in MG contrast with the abnormal results usually observed in subjects with psychotic and dissociative disorders.

Pineal gland and schizophrenia: A systematic review and meta-analysis.

Melatonin (MLT), the main hormone of the pineal gland (PG), is assumed to support initiation and maintenance of sleep, and a stable sleep-wake cycle, exerting antioxidative and neuroprotective actions. Evidence demonstrates that sleep and circadian rhythm abnormalities are very common in schizophrenia patients. Some imaging studies suggest structural abnormalities of the PG in these patients as well. We aimed to critically appraise the literature on PG imaging and melatonin secretion in schizophrenia patients, in comparison to matched healthy controls, and to review placebo-controlled trials of add-on exogenous MLT treatment in schizophrenia patients. In this systematic review, twenty-nine studies were included. Meta-analytical evaluation of data was possible only for MLT secretion finding that midnight plasma levels were significantly reduced in individuals with schizophrenia as compared to healthy controls (Hedge`s g = 1.32, p < 0.01). Imaging studies demonstrated greater prevalence of enlarged calcifications (>1 cm) of the PG (2 out of 2 computed tomography studies) and smaller PG volume (2 out of 3 magnetic resonance studies) compared with healthy controls. Anatomic and functional abnormalities of the PG were not associated with duration of illness or with treatment factors, maybe suggesting them to be primary characteristics of the disease and genetically based. Add-on MLT treatment leads to a modest improvement of objective and subjective sleep quality, of metabolic adverse effects of antipsychotics, and of tardive dyskinesia symptoms in schizophrenia patients. It remains to be established whether MLT treatment in prodromal phases of the disease could prevent neurostructural abnormalities.

Comparing the Detection of Endogenous Psychedelics in Individuals With and Without Alleged Mediumistic Experiences.

CONTEXT: Mediumship is the alleged ability to communicate with deceased personalities. Previous studies have suggested that the endogenous psychotomimetic molecules bufotenine (BT) and dimethyltryptamine (DMT) may play a role in the pathogenesis of psychotic disorders. Distortion of perceptions observed during spiritual experiences could supposedly relate to these substances. OBJECTIVE: To compare the presence of BT and DMT in human urine samples between individuals with and without mediumistic experiences. METHODS: All participants (5 from medium's group - MG and 5 from non-medium's group - CG) undertook a single night continuous 6-h urine pool collection (6:00-11:59 PM). Mediums collected urine samples in nights when they reported having experienced mediumistic communication. A sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay was used. Questionnaires were used to detect common mental disorders symptoms, and to screen and quantify anomalous experiences. RESULTS: DMT was not detected in any urine specimen tested. The presence of BT detection in urine samples was greater in CG (2/5) than in MG (1/5), with no significant differences (p > 0.99). MG reported more anomalous experiences than CG (6.6±0.8 vs. 2.2±1.5, p = 0.03), but there was no difference concerning their mental health. CONCLUSION: There were no differences between individuals with and without alleged mediumistic experiences concerning endogenous psychedelics. Both BT and DMT are highly sensitive to metabolism by monoamine oxidase and to N-oxidation, and do not survive in the periphery for long. Alternative strategies should be considered to further investigate the putative role of the endogenous psychedelics pathway for the spiritual experiences.

Lutein and zeaxanthin toxicity with and without brilliant blue in rabbits.

PURPOSE: To evaluate the safety profile of solutions containing lutein and zeaxanthin alone or associated with brilliant blue (BB). METHODS: Twenty-eight New Zealand rabbits were used to evaluate 4 concentrations of the various dye solutions: 0.5% lutein/zeaxanthin; 0.5% lutein/zeaxanthin associated with 0.0125% BB; 0.3% lutein/zeaxanthin associated with 0.025% BB; and 0.25% lutein/zeaxanthin associated with 0.05% BB. The pHs of the dye solutions ranged from 6.5 to 7.2 and the osmolarities from 280 to 320 mOsm/mL. Each rabbit had 0.1 mL of one of the dyeing solutions injected into the vitreous cavity of the right eye, while balanced salt solution (BSS) was injected into the left eye as the control. Scotopic electroretinography responses were recorded in all eyes at different time points. The animals were sacrificed at 1 and 7 days after injection; the eyes were analyzed by light and transmission electron microscopy. RESULTS: No significant (P>0.05) differences were seen in the a- and b-wave amplitudes among groups at any given point in time. Light and electron microscopy findings showed no significant abnormalities either, and were similar to the histological findings after intravitreal BSS injection. CONCLUSIONS: Lutein and zeaxanthin alone or in association with BB showed a good safety profile in this experimental model.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells.

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Effect of treatment with cyclophosphamide in low doses upon the onset of delayed type hypersensitivity in mice chronically infected with Trypanosoma cruzi: involvement of heart interstitial dendritic cells

Acute infection with Trypanosoma cruzi results in intense myocarditis, which progresses to a chronic, asymptomatic indeterminate form. The evolution toward this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi infection. Suppression of delayed type hypersensitivity (DTH) has been proposed as a potential explanation of the indeterminate form. We investigated the effect of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the participation of heart interstitial dendritic cells (IDCs) in this process using BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL (20 mg/kg body weight) for one month. A DTH skin test was performed by intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed increased thickness in antigen-injected footpads, which was more evident in the mice treated with CYCL than in those mice that did not receive treatment. The thickened regions were characterised by perivascular infiltrates and areas of necrosis. Intense lesions of the myocardium were present in three/16 cases and included large areas of necrosis. Morphometric evaluation of lymphocytes showed a predominance of TCD8 cells. Heart IDCs were immunolabelled with specific antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these cells using specific anti-T. cruzi antibodies was done, showing a significant increase in the number of these cells in treated mice. These results indicate that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi infection.

Presença de células dendríticas ativadas e das células T CD4+CD25hi na miocardite aguda e crônica da doença de chagas, em camundongos de linhagens resistente e susceptível / Presence of activated dendritic cells and CD4 + CD25hi T cells in acute and chronic myocarditis of Chagas disease in mice resistant and susceptible strains

A doença de Chagas é caracterizada por apresentar duas fases com curso clínico bastante variável. Na fase aguda ocorre uma intensa miocardite, sendo o parasita facilmente detectado no sangue periférico e nos tecidos. A fase crônica cardíaca é caracterizada por uma cardiopatia, com intensa destruição das fibras cardíacas, presença de áreas de fibrose e escassos parasitas. Os mecanismos envolvidos na patogenia dessa miocardite ainda não são muito claros. Acredita-se que as células reguladoras e as células dendríticas estejam envolvidas nesse processo. Para compreender os mecanismos envolvidos, na resposta inflamatória à infecção pelo T. cruzi, resolvemos investigar a participação das células dendríticas, das células reguladoras e o perfil dos linfócitos T CD4+ e CD8+, utilizando duas linhagens de camundongos isogênicos, que apresentam diferentes graus de susceptibilidade a infecção. Em nossos resultados constatamos que os camundongos DBA/1 apresentaram maior sobrevida à fase aguda (90%), mesmo tratando os camundongos A (70%) com benzonidazol por três dias consecutivos, com o intuito de diminuir a carga parasitária prevenindo a alta mortalidade. A resistência dos DBA/1 e a susceptibilidade dos A, a infecção pelo T. cruzi, estaria relacionada ao perfil da resposta inflamatória e regulatória desenvolvida no decorrer da doença. Observamos que os camundongos DBA/1 possuem mais células dendríticas ativadas no baço e coração e mais células T CD4+CD25hi do que os camundongos da linhagem A. Essa diferença do perfil de resposta pode estar provocando uma maior expansão e diferenciação dos linfócitos T CD4+ pelas células dendríticas, levando ao controle da carga parasitaria

Chagas’diseasse, due to Trypanosoma cruzi infection is characterized by the development of two phases with a variable clinical course. During the acute phase there occurs a severe myocarditis with the parasite being easily detected in peripheral blood and tissues. The chronic cardiac phase is characterized as a chronic cardiopathy, when severe destruction of cardiac myocells and fibrosis are present and parasites are rare. The mechanisms involved in the pathogenesis of this myocarditis are somewhat obscure. It is believed that regulatory and dendritic cells play a role in this process. In an attempt to clarify the mechanisms involved in the inflammatory response to infection with T. cruzi we decided to investigate the participation of dendritic and regulatory cells and of TCD4 and TCD8 lymphocytes, using two strains of isogenic mice , which exhibit different degrees of susceptibility to infection. Our results have shown that the DBA/1 mice presented a higher survival (90%) in the acute phase than the A mice (70%), even when these were treated with Benznidazole for three consecutive days, with the objective of to reduce the parasitemia and the high mortality. Resistance of DBA/1 mice and susceptibility of A mice could be related to the evolution of the inflammatory and regulatory responses, during the infection. It was seen that DBA/1 mice disclosed a higher number of activated dendritic cells in the spleen and heart and a higher number of T CD4+CD25hi than the mice of A strain. This differences of the response could be influencing in the TCD4 differentiation and on the control of parasitic load.

Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice.

We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.

Trypanosoma cruzi: parasite antigens sequestered in heart interstitial dendritic cells are related to persisting myocarditis in benznidazole-treated mice

We investigated whether sequestered Trypanosoma cruzi antigens found in heart interstitial dendritic cells (IDCs) contribute to the residual myocarditis found in mice following treatment with benznidazole, a specific chemotherapeutic drug. IDCs are antigen-presenting cells that are MHC-II-receptor dependent. Swiss mice were divided into two experimental groups: the 1st group was infected with the Colombian strain of T. cruzi, which is resistant to treatment with benznidazole, and the 2nd group was infected with clone 21SF-C 3, which has a medium susceptibility to the drug. Treatment of the Colombian strain group started on the 120th day post-infection and for the 21SF-C3 strain group treatment was started on the 90th day. In both groups, treatment lasted for 90 days. The animals were sacrificed either 150 or 200 days post-treatment. The myocardium was analysed by immunohistochemistry using anti-MAC3, 33D1, CD11b and CD11c monoclonal antibodies for IDCs or anti-T. cruzi purified antibodies. Parasite antigens were expressed on the IDC membranes in both treated and untreated mice. Myocarditis subsided following treatment, evidenced by both histological and morphometrical evaluation. A reduction in the number of IDCs carrying T. cruzi antigens in the treated group indicates that the elimination of parasites influences antigen presentation with concomitant decreases in inflammation. There is a correlation between the presence of T. cruzi antigens in these cells and the chronic focal, residual myocarditis seen in treated mice.

Altered cardiovascular vagal responses in nonelderly female patients with subclinical hyperthyroidism and no apparent cardiovascular disease.

OBJECTIVE: Subclinical hyperthyroidism (SH) has been associated with exercise intolerance, changes in cardiac morphology, atrial arrhythmias and sympathovagal imbalance. The aim of this study was to evaluate the vagal reserve and modulation by a sympathetic stimulus in nonelderly patients with SH without cardiovascular problems. DESIGN: We carried out a cross-sectional study, comparing data of the heart rate variability (HRV) of SH patients and healthy controls at rest and after vagal and sympathetic stimulation. PATIENTS: We studied 16 female patients with at least 6 months of SH and 16 healthy female controls with the same median age (40 vs. 34.5 years). MEASUREMENTS: We used the tilt test, with electrocardiographic record at rest, during the respiratory sinus arrhythmia (RSA) manoeuvre and after tilting, in order to analyse HRV in the frequency domain (%high frequency (HF) and low/high frequency ratio (LF/HF) using Biopotentials Captation System software. RESULTS: The median TSH level was 0.03 mU/l in patients and 1.37 mUI/l in controls. The median free T4 was 1.37 ng/dl in patients and 1.20 ng/dl in controls. Patients demonstrated a significantly smaller difference between %HF during the RSA and %HF at rest than controls (median -7.5 vs. 36.6, P < 0.001). There was a lower difference between LF/HF ratio after tilting and LF/HF ratio at rest in patients than in controls (1.5 vs. 5.3, P = 0.005). CONCLUSION: Subclinical hyperthyroidism affects cardiovascular autonomic balance in otherwise apparently healthy nonelderly females by blunting vagal responses.

Exercise performance in young and middle-aged female patients with subclinical hyperthyroidism.

Subclinical hyperthyroidism (SH) may be responsible for many cardiovascular changes, including an impaired exercise performance. The aim of our study was to evaluate the response to the treadmill cardiopulmonary test in patients with SH. We studied 14 female patients from our endocrine clinic with exogenous SH, free from cardiovascular diseases, with mean age of 38.6 +/- 10.2 years, body mass index (BMI) of 24.4 +/- 4.0 kg/m(2), and disease duration of 4.9 +/- 4.9 years. The mean serum thyrotropin (TSH) was 0.03 +/- 0.03 mU/L, serum free thyroxine (FT(4)), 1.72 +/- 0.21 ng/dL, and serum triiodothyronine level, 137 +/- 32 ng/dL. The control group comprised 15 euthyroid, healthy women, with mean age of 35.4 +/- 7.4 years and BMI of 27.3 +/- 5.9 kg/m(2). Both groups had a sedentary lifestyle and underwent the cardiopulmonary test using a treadmill with the Balke protocol. Gas concentrations and the respiratory outflow were measured and the electrocardiogram (ECG) was registered in real time. We calculated the minute ventilation (V(E)), the oxygen consumption (peak VO(2)), the carbonic gas exhalation (peak VCO(2)) and the anaerobic threshold (AT). The heart rate (HR) at rest (90.9 +/- 15.7 versus 78.9 +/- 8.7 beats per minute; p = 0.03) was higher in the patients from our clinic. There was no difference between groups regarding age, BMI, fat percentage, blood pressure, peak HR, exercise duration, mean treadmill peak inclination, V(E), peak VO(2), peak VCO(2), and AT. There was no correlation between peak VO(2) and FT(4), TSH, or disease duration. Our results show that exercise capacity in young and middle-aged female patients is not significantly affected by exogenous SH.

Investigação sobre o papel dos antígenos parasitários na patogenia da miocardite crônica, em camundongos infectados pelo Trypanosoma cruzi: a importância das células dendríticas intersticiais do miocárdio / Research on the role of parasitic antigens in pathogenesis of chronic myocarditis in mice infected with Trypanosoma cruzi: the importance of dendritic cells myocardial interstitial

A doença de Chagas, evolui em diferentes fases: aguda, com sintomas gerais e comprometimento cardíaco devido ao parasitismo pelo T. cruzi, das miocélulas cardíacas e sua rotura o que determina intensa miocardite, pela presença dos parasitos e por mecanismos imunes. Após a fase aguda, os pacientes passam a uma forma indeterminada com escassos parasitos e lesões miocárdicas focais e discretas. Os pacientes na forma indeterminada, em 40% dos casos, evoluem para uma forma crônica cardíaca. Nesta forma, os parasitos são raros nas miocélulas cardíacas, porém uma miocardite crônica difusa e fibrosante se instala, evoluindo para a insuficiência cardíaca e o óbito. A patogenia das lesões cardíacas é controvertida, sendo atribuída ao parasito o papel de estimular a resposta imune ou a um mecanismo de autoimunidade. No presente trabalho, utilizando-se o modelo do camundongo, procura-se investigar o papel dos antígenos parasitários na manutenção das lesões da fase crônica da infecção pelo T. cruzi, pela pesquisa de parasitos e de antígenos parasitários em focos inflamatórios ou pela demonstração de antígenos seqüestrados e expressos na membrana de células dendríticas intersticiais do miocárdio (CDls), pela marcação in situ, por métodos imunohistoquimicos, utilizando anticorpo anti-T.cruzi. Em camundongos cronicamente infectados, tratados com quimioterápico específico, as lesões histopatológicas regridem, permanecendo, entretanto um processo inflamatório residual. Foi desenvolvida uma investigação, com o objetivo de esclarecer, em camundongos cronicamente infectados, tratados e não tratados com o Benzonidazol, a presença de parasitos ou de seus antígenos, em focos de destruição de miocélulas parasitadas ou capturadas por CDls, e a sua relação com a persistência de infiltrados inflamatórios residuais no coração. Foram utilizados camundongos Suíços infectados com a cepa Colombiana (resistentes ao Benzonidazol) ou com um clone da 21SF (susceptível) tratados na fase crônica a partir de 90 e 120 dias de infecção durante 90 dias. O inóculo para ambos os Grupos experimentais foi de 104 formas saguícolas do T. cruzi por via intraperitoneal. Os camundongos tratados foram sacrificados 150 ou 200 dias após o tratamento, juntamente com os controles não tratados. Foram realizados os testes de cura parasitemia, subinoculação em camundongos recém-nascidos, (hemocultura, sorologia). Secções de coração e de músculo esquelético foram fixadas e processadas para estudo histopatológico em secções coradas pela Hematoxilina e Eosina ou pelo método do Picro-Sirius para colágeno e para imunohistoquímica com anticorpos anti-T. cruzi e anti-MAC. Os resultados mostraram na infecção crônica pela cepa Colombiana lesões inflamatórias, moderadas a intensas, com necrose de miocélulas cardíacas e infiltrados mononucleares e fibrose intersticial difusa e focal. Nos tratados, houve regressão parcial das lesões permanecendo infiltrados inflamatórios residuais que variaram de discretos a moderadas e sinais de regressão da fibrose. Na infecção crônica pelo clone 21SF C3 havia miocardite crônica difusa discreta ou moderada na maioria dos casos. Nos tratados, houve decréscimo das lesões inflamatórias, com sinais de regressão da fibrose. Testes imunohistoquimicos com anticorpos anti- T.cruzi revelaram detritos parasitários positivos em focos inflamatórios. As CDls do miocárdio apresentaram em todos os casos, marcação positiva para antígeno do T. cruzi, comprovando o papel das células apresentadoras de antígenos na manutenção das lesões na fase crônica da infecção.

Prevalência de sobrepeso e obesidade em pacientes com diabetes tipo 1 / Prevalence of overweight and obesity in type 1 diabetic patients

Para avaliar a prevalência de sobrepeso e obesidade em diabéticos tipo 1 (DM1), estudamos 170 pacientes (89F/81M; 14 crianças, 51 adolescentes e 105 adultos, com 24,4±11,9 anos) e correlacionamos seus dados antropométricos com fatores demográficos e clínicos. A prevalência de obesidade, sobrepeso e/ou risco de sobrepeso foi de 21,2 por cento (n= 36). Houve uma correlaçäo de 0,97 entre o score z do IMC e o percentil do IMC (p= 0,00) no grupo de crianças e adolescentes. Houve diferença na PAS (p= 0,004) e na PAD (p= 0,0007) entre pacientes com IMC normal e alterado. Ocorreu uma tendência a um aumento progressivo da medida da cintura com os níveis de PA (p= 0,0000). O IMC foi dependente da idade (OR: 1,04, 95 por cento IC = 1,01-1,07; p= 0,008) na análise multivariada. Na análise stepwise, a PAS foi dependente da cintura (r= 0,57; p= 0,00) e da idade (r= 0,63; p= 0,00) e a PAD, da cintura (r= 0,53; p= 0,00). A prevalência de sobrepeso e obesidade nos DM1 parece refletir a tendência mundial de aumento de peso e suas conseqüências clínicas, reforçando a necessidade do controle de peso nestes pacientes.

Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias.

Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease.

Treatment with benznidazole in association with immunosuppressive drugs in mice chronically infected with Trypanosoma cruzi: investigation into the possible development of neoplasias

Benznidazole is recommended in Brazil for the treatment of Trypanosoma cruzi infection in acute and early chronic phases of Chagas' disease. Observations by others have indicated a higher incidence of neoplasias in immunosuppressed patients, presenting Chagas' disease reactivation, submitted to treatment with benznidazole. In the present study, we investigated whether there is a potentiation in the generation of lymphomas in chronically infected mice, treated with immunosuppressive drugs and benznidazole. For this, 142 Swiss mice chronically infected with the 21 SF strain of T. cruzi and 72 normal Swiss mice were used. Both infected and normal mice were divided into experimental groups and submitted to one of the following treatment regimens: benznidazole alone; immunosuppressive drugs (azathioprine, betamethasone and cyclosporin); a combination of immunosuppressive drugs and benznidazole; and untreated controls. In the infected group treated with benznidazole, one mouse developed a non-Hodgkin's lymphoma. This finding has been interpreted as a spontaneous tumor of mice. The study of the chronically infected mice treated with the combination of immunosuppressive drugs and benznidazole demonstrated an absence of lymphomas or other neoplasias. These findings support the indication of benznidazole, as the drug of choice, for immunosuppressed patients that develop a reactivation of Chagas' disease