Aurelio López-Colombo

Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals.

Understanding the pathogenic mechanisms in chronic Chagas disease, a major cause of morbidity and mortality in Latin America, is essential for the design of rational therapeutic strategies. In this paper we show that the development of Chagas disease is a consequence of a long-term and complex relationship between parasite persistence and maladapted homeostatic mechanisms in the host which leads to pathologic changes. We performed a retrospective study on 50 patients with chronic Chagas disease and 50 healthy control individuals. The specific immune response was detected by ELISA and IHA tests using autochthonous antigens, inflammatory process with the cytokine tumour necrosis factor (TNF)-alpha and nitric oxide (NO), and antioxidant protection with glutathione peroxidase and superoxide dismutase (SOD) levels. We developed generalised linear modelling procedures to assess simultaneously which explanatory variables and/or their interactions better explained disease severity in patients. Our results show the existence of a strong relationship between anti-Trypanosoma cruzi levels and chronic Chagas disease (P<0.0001). Taken together, the statistical data indicate both cumulative and complementary effects, where the increase in TNF-alpha (P=0.004) and NO (P=0.005) levels correlated with a reduction in glutathione peroxidase (P=0.0001) and SOD (P=0.01) levels drives the disease pathology in chronically infected patients. Our findings may have important implications for understanding host susceptibility to develop severe chronic infectious disease. In addition we show putative targets for the design of new therapeutic strategies to prevent disease progression, considering both specific treatment against the aetiological agent and modulation of the different immunopathological reactions in chronically infected individuals with chronic Chagas disease.

Anti-CD20 therapy in patients with refractory systemic lupus erythematosus: a longitudinal analysis of 52 Hispanic patients

The objective of this study was to investigate the efficacy and safety of anti-CD20 treatment in Hispanic patients with refractory systemic lupus erythematosus and to determine whether baseline parameters predict disease flare. Fifty-two patients with systemic lupus erythematosus, 13 with active lupus nephritis, eight with thrombocytopenia, three with leukocytopenia, 25 with severe musculoskeletal involvement and three with skin involvement) refractory to conventional therapy were treated with anti-CD20 treatment (rituximab; MabThera®, Roche) plus ongoing immunosuppressive treatment. Disease activity was assessed monthly using the SLEDAI validated for the Mexican population with a follow-up period of 6 months. At 6 months of follow-up, significant clinical improvements were detected, with a reduction in the global SLEDAI validated for the Mexican population score. Five of the 13 patients with lupus nephritis (38.4%) had a complete renal response and five (38.4%) had a partial response. Rituximab was also effective in patients with autoimmune thrombocytopenia, inducing a significant increase in platelet counts (p = 0.012). Nineteen of 25 patients with severe musculoskeletal involvement had remission of arthritis. Only one of the three patients with skin involvement had no lesions at 6 months. Rituximab treatment also allowed a reduction of the oral prednisone dose in the majority of patients. No baseline predictors of flare were found. Treatment was discontinued after the first infusion in two patients due to serum sickness and in another due to pulmonary infection. In conclusion, the addition of rituximab to conventional immunosuppressive therapy may be an effective strategy for lupus nephritis, autoimmune thrombocytopenia and inflammatory polyarthritis in patients with refractory systemic lupus erythematosus. Lupus (2010) 19, 213—219.

Use of rituximab in patients with systemic lupus erythematosus: An update

Systemic lupus erythematosus (SLE) is a chronic, occasionally life threatening, multisystem disorder. Patients suffer from a wide group of symptoms and have a variable prognosis that depends of the severity and type of organ involvement. The clinical manifestations include fever, skin lesions, arthritis, neurologic, renal, cardiac, and pulmonary disease. The pathogenesis of this serious multisystem autoimmune disease is based on polyclonal B cell immunity, which involves connective tissue and blood vessels. The novel biologic therapies have raised hope for more effective and safer treatment for SLE. Although definitive studies are still under development, the impressive preliminary results of therapies specifically targeting B cells and the signaling pathways involved in B-T-cell interactions suggest that the depletion of memory cells accounts, at least in part, for the clinical efficacy of rituximab therapy in patients whose disease is resistant to other immunosuppressive therapies. However these findings, although provocative, require further investigation in larger cohorts.

The Epidemiology of Functional Gastrointestinal Disorders in Mexico: A Population-Based Study

Aims. The frequency of functional gastrointestinal disorders (FGIDs) in the general population of Mexico is unknown. Methods. To determine the prevalence of FGIDs, associated depression, and health care utilization, a population-based sampling strategy was used to select 500 households in the State of Tlaxcala, in central Mexico. Household interviews were conducted by two trained physicians using the Rome II Modular Questionnaire, a health-care and medication used questionnaire and the CES-D depression scale. Results. The most common FGIDs were IBS: 16.0% (95% CI: 12.9–19.5); functional bloating: 10.8% (8.2–13.9); unspecified functional bowel disorder: 10.6% (8.0–13.6); and functional constipation (FC): 7.4% (5.3–10.1). Uninvestigated heartburn was common: 19.6% (16.2–23.4). All FGIDs were equally prevalent among both genders, except for IBS (P = 0.001), IBS-C (P < 0.001), IBS-A/M (P = 0.049), and FC (P = 0.039) which were more frequent in women. Subjects with FGIDs reported higher frequencies of medical visits: 34.6 versus 16.8%; use of medications: 40.7 versus 21.6%; (both P < 0.001); and reported depression: 26.7 versus 6.7%, (P < 0.001). Conclusion. In this first population-based study of FGIDs in Mexico, heartburn, IBS, functional distension, and FC were common. Only IBS, IBS-C, IBS-A/M, and FC were more frequent in women. Finally, FGIDs in Mexico had an increased burden of health care utilization and depression.

Correlation of the serum concentrations of tumour necrosis factor and nitric oxide with disease severity in chronic Chagas disease (American trypanosomiasis)

Abstract Pro-inflammatory cytokines such as tumour necrosis factor (TNF) and nitric oxide (NO) are believed to play an important role in the severity of chronic disease. When evaluated in 71 patients who were seropositive for Trypanosoma cruzi and 50 apparently healthy controls, the mean (S.D.) serum concentrations of both TNF [7.65 (1.32) ν. 4.24 (1.53) ng/ml; P<0.001] and NO [114 (40) ν. 74 (21) μM; P<0.0001] were found to be significantly higher in the patients than in the controls. In addition, patients with chronic, symptomatic disease affecting their hearts — eight with dilated cardiomyopathy [8.82 (1.47) ng TNF/ml; 142 (45) μM NO] and 17 others with electrocardiographic alterations [8.37 (1.26) ng TNF/ml; 134 (53) μM NO] — had significantly higher serum concentrations of these cytokines than 34 patients who were in the asymptomatic, indeterminate phase of the disease [6.38 (1.35) ng TNF/ml; 99 (28) μM NO]. In those infected with T. cruzi, it therefore appears that serum concentrations of TNF and NO correlate with disease severity, indicating that these cytokines play some role in the pathogenesis of chronic Chagas disease.

Clinical forms of Trypanosoma cruzi infected individuals in the chronic phase of Chagas disease in Puebla, Mexico

In Mexico, despite the relatively high seroprevalence of Trypanosoma cruzi infection in humans in some areas, reported morbidity of Chagas disease is not clear. We determined clinical stage in 71 individuals seropositive to T. cruzi in the state of Puebla, Mexico, an area endemic for Chagas disease with a reported seroprevalence of 7.7%. Diagnosis of Chagas disease was made by two standardized serological tests (ELISA, IHA). Individuals were stratified according to clinical studies. All patients were submitted to EKG, barium swallow, and barium enema. Groups were identified as indeterminate form (IF) asymptomatic individuals without evidence of abnormalities (n = 34 cases); those with gastrointestinal alterations (12 patients) including symptoms of abnormal relaxation of the lower esophageal sphincter and absent peristalsis in the esophageal body, grade I megaesophagus, and/or megacolon; patients with clinical manifestations and documented changes of chronic Chagas heart disease who were subdivided as follows: mild (8 patients)--mild electrocardiographic changes of ventricular repolarization, sinus bradychardia); moderate (6 patients)--left bundle branch block, right bundle branch block associated with left anterior fascicular block); severe (8 patients)--signs of cardiomegaly, dilated cardiomyopathy); and the associated form (3 cases) that included presence of both cardiomyopathy and megaesophagus. These data highlight the importance of accurate evaluation of the prevalence and clinical course of Chagas disease in endemic and non-endemic areas of Mexico.

Trypanosoma cruzi strains isolated from human, vector, and animal reservoir in the same endemic region in Mexico and typed as T. cruzi I, discrete typing unit 1 exhibit considerable biological diversity

In this study, three strains of Trypanosoma cruzi were isolated at the same time and in the same endemic region in Mexico from a human patient with chronic chagasic cardiomyopathy (RyC-H); vector (Triatoma barberi) (RyC-V); and rodent reservoir (Peromyscus peromyscus) (RyC-R). The three strains were characterized by multilocus enzyme electrophoresis, random amplified polymorphic DNA, and by pathological profiles in experimental animals (biodemes). Based on the analysis of genetic markers the three parasite strains were typed as belonging to T. cruzi I major group, discrete typing unit 1. The pathological profile of RyC-H and RyC-V strains indicated medium virulence and low mortality and, accordingly, the strains should be considered as belonging to biodeme Type III. On the other hand, the parasites from RyC-R strain induced more severe inflammatory processes and high mortality (> 40%) and were considered as belonging to biodeme Type II. The relationship between genotypes and biological characteristics in T. cruzi strains is still debated and not clearly understood. An expert committee recommended in 1999 that Biodeme Type III would correspond to T. cruzi I group, whereas Biodeme Type II, to T. cruzi II group. Our findings suggest that, at least for Mexican isolates, this correlation does not stand and that biological characteristics such as pathogenicity and virulence could be determined by factors different from those identified in the genotypic characterization.

Primary antiphospholipid syndrome in Latin American mestizo patients: clinical and immunologic characteristics and comparison with European patients

A great variety of clinical and immunological features have been described in patients with the antiphospholipid syndrome (APS), but information on their prevalence and characteristics in Latin American mestizo patients with the primary APS is scarce. To analyze the prevalence and characteristics of the main clinical and immunological manifestations in a cohort of patients with primary APS of mestizo origin from Latin America and to compare them with the European white patients, clinical and serological characteristics of 100 patients with primary APS from Colombia, Mexico, and Ecuador were collected in a protocol form that was identical to that used to study the “Euro-Phospholipid” cohort. The cohort consisted of 92 female patients (92.0%) and eight (8.0%) male patients. They were all mestizos. The most common manifestations were deep vein thrombosis (DVT; 23.0%), livedo reticularis (18.0%), migraine (18.0%), and stroke (18.0%). The most common pregnancy morbidity was early pregnancy losses (54.1% of pregnancies). Several clinical manifestations were more prevalent in the Latin American mestizo than in the European patients (transient global amnesia, pulmonary microthrombosis, arthralgias, and early pregnancy losses) and vice-versa (DVT, stroke, pulmonary embolism, and thrombocytopenia). Latin American mestizo patients with primary APS have a wide variety of clinical and immunological manifestations with several differences in their prevalence in comparison with European white patients.

Microbiota, infecciones gastrointestinales, inflamación de bajo grado y antibioticoterapia en el síndrome de intestino irritable. Una revisión basada en evidencias

BACKGROUND Post-infectious irritable bowel syndrome (PI-IBS) prevalence, small intestinal bacterial overgrowth (SIBO), altered microbiota, low-grade inflammation, and antibiotic therapy in IBS are all controversial issues. AIMS To conduct an evidence-based review of these factors. METHODS A review of the literature was carried out up to July 2012, with the inclusion of additional articles as far as August 2013, all of which were analyzed through the Oxford Centre for Evidence-Based Medicine (OCEBM) system. RESULTS 1.There is greater SIBO probability in IBS when breath tests are performed, but prevalence varies widely (2-84%). 2.The gut microbiota in individuals with IBS is different from that in healthy subjects, but a common characteristic present in all the patients has not been established. 3.The incidence and prevalence of PI-IBS varies from 9-10% and 3-17%, respectively, and the latter decreases over time. Bacterial etiology is the most frequent but post-viral and parasitic cases have been reported. 4.A sub-group of patients has increased enterochromaffin cells, intraepithelial lymphocytes, and mast cells in the intestinal mucosa, but no differences between PI-IBS and non-PI-IBS have been determined. 5.Methanogenic microbiota has been associated with IBS with constipation. 6.Rifaximin at doses of 400mg TID/10days or 550mg TID/14days is effective treatment for the majority of overall symptoms and abdominal bloating in IBS. Retreatment effectiveness appears to be similar to that of the first cycle. CONCLUSIONS Further studies are required to determine the nature of the gut microbiota in IBS and the differences in low-grade inflammation between PI-IBS and non-PI-IBS. Rifaximin has shown itself to be effective treatment for IBS, regardless of prior factors.

Treatment of vitiligo with a chimeric monoclonal antibody to CD20: a pilot study

Five patients with active disseminated vitiligo were given 1 g of a chimeric (murine/human) monoclonal antibody to CD20 in a single intravenous infusion and followed‐up for 6 months. Three of the patients showed an overt clinical and histological improvement of the disease, one presented slight improvement and the remaining patient showed no changes. Improvement was neither associated with changes in laboratory parameters nor to a specific human leucocyte antigen D‐related (HLA‐DR) phenotype. We believe that these preliminary results are encouraging, and further clinical trials should be undertaken. An important aim should be the finding of a marker with a good response to this therapeutic approach.