Evolutionary cardiology and experimental research

Evolutionary medicine studies the role of evolution in health problems. Diseases are considered as phenotypes generated by the expression of sets of genes and a complex interplay with the environment. The main mechanisms involved in evolutionary medicine are antagonistic pleiotropy, ecological antagonistic pleiotropy, atavisms and heterochrony. Antagonistic pleiotropism refers to genes that are beneficial during certain stages of development but become detrimental in others. Ecological antagonistic pleiotropy refers to the misadaptation to current lifestyle conditions which are different from those in which humans evolved. These mechanisms participate in the development of congestive heart failure, hypertension and atherosclerosis. Atavistic conditions or genes are expressed in our ancestors but have remained silent during evolution being suddenly expressed without an apparent cause during the appearance of a disease is another mechanism in evolutionary cardiology. The change in the heart metabolism from fatty acid to glucose dependent can be considered as an atavistic condition that appears in the heart after a stroke and may underlie impaired cardiomyocyte regeneration. Heterochrony is the expression of genes that cause the appearance of traits at a different timing during development and is therefore related to atavisms. Evolutionary medicine explains the interactions of pathogens and the host in infectious diseases where the cardiac tissue becomes a target. Mechanisms involved in evolutionary medicine participate in the generation of diseases and may be approached experimentally. Therefore, to better understand health problems and therapeutical approaches, an evolutionary medicine approach in experimental medicine may prove useful.     

Evaluation of polylactic acid nanoparticles safety using Drosophila model

Cytotoxicity of nanoparticles and their sub-lethal effect on cell behavior and cell fate are a high topic of studies in the nanomaterial field. With an explosion of nanoparticle types (size, shape, polarity, stiffness, composition, etc.), Drosophila has become an attractive animal model for high throughput analysis of these nanocarriers in the drug delivery field with applications in cancer therapy, or simply to generate a fast and complete cytotoxic study of a peculiar nanoparticle. In respect to that, we have conducted an in cellulo study of poly(lactic acid) (PLA) nanoparticle cytotoxicity, and determined that near lethal nanoparticle doses, oxidative stress as well as P53 and ATP pathways may lead to cell cycle arrest at G1, and ultimately to cell death. Neither viability nor the development of Drosophila larvae are affected by the ingestion of PLA nanoparticles at sub-lethal concentrations. Drosophila will be a useful model to study PLA and PLA-modified nanoparticle toxicity, and nanoparticle fate after ingestion.     

Predominance of lineage I among Trypanosoma cruzi isolates from Venezuelan patients with different clinical profiles of acute Chagas' disease

Trypanosoma cruzi isolates from 23 acute chagasic patients from localities of Western Venezuela (state of Barinas) where Chagas' disease is endemic were typed using ribosomal and mini-exon gene markers. Results showed that isolates of the two major phylogenetic lineages, T. cruzi I and T. cruzi II, were isolated from these patients. Six isolates (26%) were typed as T. cruzi II and 17 (74%) as belonging to T. cruzi lineage I. Analysis of random amplified polymorphic DNA (RAPD) patterns confirmed these two groups of isolates, but did not disclose significant genetic intra-lineage polymorphism. Patients infected by both T. cruzi I or T. cruzi II showed different clinical profiles presenting highly variable signs and symptoms of acute phase of Chagas' disease ranging from totally asymptomatic to severe heart failure. The predominance of T. cruzi I human isolates in Venezuela allied to the higher prevalence of severe symptoms of Chagas' disease (heart failure) in patients infected by this lineage do not corroborate an innocuousness of T. cruzi I infection to humans. To our knowledge, this is the first study describing predominance of T. cruzi lineage I in a large number of acute chagasic patients with distinct and well-characterized clinical profiles.     

Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice

Nonexudative age-related macular degeneration (NE-AMD) represents the leading cause of blindness in the elderly. Currently, there are no available treatments for NE-AMD. We have developed a NE-AMD model induced by superior cervical ganglionectomy (SCGx) in C57BL/6J mice, which reproduces the disease hallmarks. Several lines of evidence strongly support the involvement of oxidative stress in NE-AMD-induced retinal pigment epithelium (RPE) and outer retina damage. Melatonin is a proven and safe antioxidant. Our aim was analysing the effect of melatonin in the RPE/outer retina damage within experimental NE-AMD. The treatment with melatonin starting 48 h after SCGx, which had no effect on the ubiquitous choriocapillaris widening, protected visual functions and avoided Bruch´s membrane thickening, RPE melanin content, melanosome number loss, retinoid isomerohydrolase (RPE65)-immunoreactivity decrease, and RPE and hotoreceptor ultrastructural damage induced within experimental NE-AMD exclusively located at the central temporal (but not nasal) region. Melatonin also prevented the increase in outer retina/RPE oxidative stress markers and a decrease in mitochondrial mass at 6 weeks post-SCGx. Moreover, when the treatment with melatonin started at 4 weeks post-SCGx, it restored visual functions and reversed the decrease in RPE melanin content and RPE65-immunoreactivity. These findings suggest that melatonin could become a promising safe therapeutic strategy for NE-AMD.     

Analysis of hepatitis C virus-positive organs in liver transplantation.

The authors of this study note that in liver transplantation (LT), the survival rates of hepatitis C virus (HCV)-positive donors and HCV-negative receivers are comparable to those of HCV-negative donors and recipients. Direct-acting antiviral (DAA) therapies have nearly 100% effectiveness in treating HCV. Between 2006 and 2016, the percentages of HCV-positive patients on the waiting list and HCV-positive LT recipients fell by 8.2 percent and 7.6 percent, respectively. Records from April 1, 2014, in which the donor and receiver were both at least 18 years old and had a positive HCV status, were the only ones eligible for the study. The analysis for this study was restricted to the first transplant recorded for each patient using a data element that documented the number of prior transplants for each recipient, although some recipients appeared multiple times in the data set. HCV-positive recipients or people with fulminant hepatic failure were the main beneficiaries of primary biliary cirrhosis among HCV-positive donors. However, there is still a reticence to use HCV-positive donor organs in HCV recipients due to clinical and ethical considerations. Similar survival rates between HCV-positive donors and recipients and HCV-negative donors and receivers illustrate the efficacy of these DAA regimens.     

Burden of influenza in Latin America and the Caribbean: a systematic review and meta‐analysis

Please cite this paper as: Savy et al. (2012) Burden of influenza in Latin America and the Caribbean: a systematic review and meta‐analysis. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12036.Objective  Influenza causes severe morbidity and mortality. This systematic review aimed to assess the incidence, etiology, and resource usage for influenza in Latin America and the Caribbean.Design  Meta‐analytic systematic review. Arcsine transformations and DerSimonian Laird random effects model were used for meta‐analyses.Setting  A literature search from 1980 to 2008 in MEDLINE, Cochrane Library, EMBASE, LILACS, Ministries of Health, PAHO, proceedings, reference lists, and consulting experts.Sample  We identified 1092 references, of which 31 were finally included, in addition to influenza surveillance reports. We also used information from the 10 reports from the collaborative group for epidemiological surveillance of influenza and other respiratory virus (GROG), and information retrieved from the WHO global flu database FLUNET.Main outcome measures  Incidence, percentage of influenza specimens out of the total received by influenza centers and resource‐use outcomes.Results  A total of 483 130 specimens of patients with influenza were analyzed. Meta‐analysis showed an annual rate of 36 080 (95%CI 28 550 43 610) influenza‐like illness per 100 000 persons‐years. The percentage of influenza out of total specimens received by influenza centers ranged between 4.66% and 15.42%, with type A the most prevalent, and A subtype H3 predominating. The mean length of stay at hospital due to influenza ranged between 5.8 12.9 days, total workdays lost due to influenza‐like illnesses were 17 150 days, and the mean direct cost of hospitalization was US$575 per laboratory‐confirmed influenza case.Conclusions  Our data show that seasonal influenza imposes a high morbidity and economic burden to the region. However, the vaccine‐uptake rate has been low in this region. Population‐based cohort studies are required to improve the knowledge about incidence and resource utilization, which would inform healthcare authorities for decision making.     

Efficacy of rifabutin-based triple therapy in Helicobacter pylori infected patients after two standard treatments

BACKGROUND AND AIM: Even with the current most effective treatment regimens for Helicobacter pylori infection, a considerable number of patients will be resistant to eradication. The aim of the present study was to evaluate the H. pylori eradication rate in patients resistant to standard therapies when treated with a triple therapy of pantoprazole, rifabutin and amoxicillin. METHODS: Ninety-two consecutive patients diagnosed with H. pylori infection resistant to two previous treatment regimens were treated with pantoprazole, rifabutin and amoxicillin for 10 days. The persistence or eradication of H. pylori was determined by a 13C-urea breath test performed 4 weeks after the treatment. RESULTS: Per protocol eradication was achieved in 62.2% of patients and the intention-to-treat eradication was 60.8%. Only two patients were excluded for adverse events related to the treatment. CONCLUSIONS: The eradication rate is acceptable as a third-line therapy, particularly in centers with high cure rate for first line therapy. Another important value of this study is the good tolerance for the treatment observed in our patients. It is possible that rifabutin-based triple therapy may be of use in hospital centers that do not have disposable culture and susceptibility methods against H. pylori.     

Development and Validation of an HIV Risk Exposure and Indicator Conditions Questionnaire to Support Targeted HIV Screening

The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated.Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin-Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial).A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non–HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items.