ENDOCYTIC TRAFFICKING OF THE AMYLOID PRECURSOR PROTEIN IN RAT CORTICAL NEURONS

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on Endosomal Sorting Complexes Required for Transport (ESCRT) machinery. This implied that APP is ubiquitinated to allow ESCRT interactions. We then identified that the endosome-associated E3 ubiquitin ligase, UBE4B, is required for efficient endosomal APP trafficking. These results suggest that the efficiency of endosomal APP trafficking regulates Aβ generation. Decreasing Aβ levels in the brain may be a mechanism for disease modification in amyloid-related dementia. These experiments elucidate cellular mechanisms that are amenable to regulation and could serve as potential therapeutic targets for amyloid pathologies

Malaria due to Plasmodium falciparum. Presentation of an imported case

Malaria is the most frequent tropical infectious disease in the world and depending on the Plasmodium subtype it may be defined its geographical distribution. The number of imported cases in the last years has increased due to the augmentation of the number of travelers from endemic zones, lack of adequate prophylaxis an the prevalence of each time higher of parasites resistant to the drugs used for their treatment. For these reasons a case of acute febrile syndrome is presented and antecedent of having arrived from Angola, country where Malaria is considered endemic and he was diagnosed malaria produced by Plasmodium falciparum. The control of imported malaria is really necessary for the risk it represents on the receptive areas which, as in Cuba, have eliminated the disease

Science, art and medicine in Cuba during the 17th and 18th centuries

Medicine is the science dedicated to the study of life, health, diseases and death of human beings, and involves exercising scientific-technical knowledge for the maintenance and recovery of health. It is an art where the knowledge of the doctor is used to obtain a practical result that is to prevent a human being from getting sick, and if he does, to achieve the restoration of his health. The art of being a doctor implies the science with which one has to proceed and through which one can find solutions to health problems through scientific methods. For its part, art, through its various manifestations such as painting, photography, sculpture, literature, among others, has facilitated medicine knowledge about facts, characters, actions or investigations carried out by illustrious personalities of medicine and science, since the emergence of medicine in Cuba during the colonial era. These precedents constitute works of invaluable historical and scientific value, which have contributed important antecedents in the execution of the current health programs

Adverse reactions to antimicrobials in patients from Las Tunas

Background: the consequences generated by the massive and unjustified use of antimicrobials currently represent serious problems in the context of public health on a worldwide scale.Objective: to describe the adverse reactions produced by antimicrobials, reported to the pharmacovigilance database in the province of Las Tunas, from January to June 2017.Methods: a pharmacovigilance, observational, descriptive and cross-sectional study was carried out at the aforementioned place and during the period herein declared. The study universe consisted of 460 reports of adverse reactions and the sample was made up of the 111 reports corresponding to antimicrobials. Descriptive statistics techniques were applied to analyze the information. The measures of summary statistics were absolute frequency and percentile.Results: the report of adverse reactions to antimicrobials remained similar in most of the studied months, reports of adverse reactions to antimicrobials in female patients predominated for 61,2 %, in the 19 to 59 age group, 42,3 %. The most affected organ system was the skin in 33,3 %, followed by the general system in 26,2 %. Mild adverse reactions predominated in 58,5 %, probable adverse reactions in 88,2 % and frequent adverse reactions in 58,5 %. The majority of the reactions were reported by physicians, 67,5 %. According to the drug class, cephalosporins and penicillins had higher reports (30,6 and 28,8 %, respectively).Conclusions: the adverse reactions produced by antimicrobial agents in patients from Las Tunas were described, in the first semester of 2017.</p

Clinical and epidemiological aspects of rabies in the province of Cienfuegos. 2016-2017

Foundation: rabies is a viral disease with a mortality of almost 100%, but avoidable by vaccination. Objective: To describe clinical and epidemiological aspects of rabies in the province of Cienfuegos, in the years 2016 and 2017. Methods: retrospective descriptive study of all the patients injured by animals in the province of Cienfuegos, during the period from January 2016 to December 2017. The variables analyzed were: municipalities of occurrence, injury severity, age groups, type of animal injury, rabies treatment, canine sanitation and rabies surveillance. The primary source for obtaining the information was injured patient´s notification cards review in the health areas of the Cienfuegos Province and data from the Department of Statistics of the Provincial Center for Hygiene Epidemiology and Microbiology of Cienfuegos. Results: 2 577 injured were reported; Lajas was the municipality with the highest number of reports in 2016 and Palmira in 2017; the risk of humans to get rabies is kept high; 87.5% of the injuries were produced by canines, of which 35.2% are street dogs. The 5-9 years pediatric ages have the highest rates; slight injuries predominated and sanitation activity was higher in 2017. Conclusion: there are still difficulties in the prevention and control of rabies, so it is important to work on the deficiencies to avoid the occurrence of cases taking into account the high lethality of this disease

Caracterización clinicoepidemiológica de pacientes con tuberculosis diagnosticada en el Hospital Provincial "Celia Sánchez Manduley"

Se realizó un estudio descriptivo, retrospectivo y longitudinal de 63 pacientes con tuberculosis, atendidos en el Hospital Clinicoquirúrgico Docente Universitario "Celia Sánchez Manduley" de Manzanillo, provincia de Granma, desde el 2009 hasta el 2011, con vistas a caracterizarles según factores clinicoepidemiológicos de interés. Entre las variables analizadas figuraron: edad, sexo, procedencia, factores de riesgo, formas clínicas de la tuberculosis, tipo de tuberculosis extrapulmonares y categoría de casos. En la casuística predominaron el sexo masculino, los grupos etarios de 45-65 años, procedentes en su mayoría de zonas rurales; la ingestión de alcohol como factor de riesgo asociado y las formas pulmonares con baciloscopia positiva como las formas clínicas más frecuentes. La mayoría de los casos notificados fueron nuevo

A Polymorphism in the FGFR4 Gene Is Associated With Risk of Neuroblastoma and Altered Receptor Degradation

BackgroundOutcomes for children with high-risk neuroblastoma are poor, and improved understanding of the mechanisms underlying neuroblastoma pathogenesis, recurrence, and treatment resistance will lead to improved outcomes. Aberrant growth factor receptor expression and receptor tyrosine kinase signaling are associated with the pathogenesis of many malignancies. A germline polymorphism in the FGFR4 gene is associated with increased receptor expression and activity and with decreased survival, treatment resistance, and aggressive disease for many malignancies. We therefore investigated the role of this FGFR4 polymorphism in neuroblastoma pathogenesis.Materials and methodsGermline DNA from neuroblastoma patients and matched controls was assessed for the FGFR4 Gly/Arg388 polymorphism by RT-PCR. Allele frequencies were assessed for association with neuroblastoma patient outcomes and prognostic features. Degradation rates of the FGFR4 Arg388 and Gly388 receptors and rates of receptor internalization into the late endosomal compartment were measured.ResultsFrequency of the FGFR4 AA genotype and the prevalence of the A allele were significantly higher in patients with neuroblastoma than in matched controls. The Arg388 receptor demonstrated slower degradation than the Gly388 receptor in neuroblastoma cells and reduced internalization into multivesicular bodies.ConclusionsThe FGFR4 Arg388 polymorphism is associated with an increased prevalence of neuroblastoma in children, and this association may be linked to differences in FGFR4 degradation rates. Our study provides the first evidence of a role for FGFR4 in neuroblastoma, suggesting that FGFR4 genotype and the pathways regulating FGFR4 trafficking and degradation may be relevant for neuroblastoma pathogenesis

Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America