Alterations in lipid profile and enzymes paraoxonase and butyrylcholinesterase in CBS-deficient patients

Homocystinuria is an inborn error of metabolism most frequently caused by cystathionine β-synthase (CBS) deficiency. Homocysteine (Hcy), methionine (Met) and other metabolites of Hcy accumulate in the body of affected patients, leading to clinical manifestations such as dislocation of the optic lents, osteoporosis, mental retardation, and thromboembolism. Despite the fact that thromboembolism represent the major cause of morbidity and the most frequent cause of death in CBS-deficient patients, the cause of cardiovascular changes found in homocystinuria remain unclear. In this work, we evaluated the lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, oxidized LDL cholesterol, apolipoprotein A-1) and the activities of the enzymes paraoxonase (PON1) and butyrylcholinesterase (BuChE) in plasma of patients with homocystinuria due CBS deficiency, at diagnosis and during the treatment. It was verified a significant decrease in HDL cholesterol and apolipoprotein A1 levels in the both groups of CBS-deficient patients (at diagnosis and under treatment) when compared to controls. PON1 activity was also significantly lower in the both groups of CBS-deficient patients when compared to controls which may be related with an Hcy-dependent oxidation of any group important to catalytic activity of the enzyme that favors the atherogenesis. BuChE activity was significantly increased only in CBS-deficient patients at diagnosis and it is known that this enzymatic activity is positively associated with cardiovascular risk factors. Evaluated together, our results demonstrated that treated or not CBS-deficient patients presented important alterations in lipid metabolism. This work contributes to the understanding of the responsible mechanisms of vascular lesions in CBS-deficient patients.Apoio: CNPq, FAPERGS, CAPES, FIPE/HCP

Impairment of energy metabolism in hippocampus of rats subjected to chemically-induced hyperhomocysteinemia

AbstractHomocystinuria is an inherited metabolic disease biochemically characterized by tissue accumulation of homocysteine (Hcy). Mental retardation, ischemia and other neurological features, whose mechanisms are still obscure are common symptoms in homocystinuric patients. In this work, we investigated the effect of Hcy administration in Wistar rats on some parameters of energy metabolism in the hippocampus, a cerebral structure directly involved with cognition. The parameters utilized were 14CO2 production, glucose uptake, lactate release and the activities of succinate dehydrogenase and cytochrome c oxidase (COX). Chronic hyperhomocysteinemia was induced by subcutaneous administration of Hcy twice a day from the 6th to the 28th day of life in doses previously determined in our laboratory. Control rats received saline in the same volumes. Rats were killed 12 h after the last injection. Results showed that Hcy administration significantly diminished 14CO2 production and glucose uptake, as well as succinate dehydrogenase and COX activities. It is suggested that impairment of brain energy metabolism may be related to the neurological symptoms present in homocystinuric patients

El Salvador: Gun Violence

El Salvador, a country about the same size as the U.S’s New Jersey and a population of over six million people, has a death rate of 5.8 per 1,000. Even after going to war in the 1980s and 1990s, El Salvador is still riddled with everyday gun violence. Due to severe gang activity, the death toll has skyrocketed and police interjection only makes it worse. The leftist government of President Salvador Sánchez Cerén, has opposed negotiations and moved gang leaders into tighter-security prisons, moves that have intensified the climate of confrontation. Plans to combat gang and gun violence has made somewhat of a difference in the past few years, but there is a long way to go before an everlasting impact is made. In order for a decrease in violence, there should be less of a push to fight it with more violence and more of a push to build a community away from fear. A move in the right direction is a crime and violence prevention project. The U.S. Agency for International Development-funded El Salvador Violence and Crime Prevention Project is addressing the troubling situation by improving the ability of communities, municipalities and national institutions to address violent crime. Creative (the organization who created the project) collaborated with the government of El Salvador to develop the National System for the Prevention of Violence Law. The following information is about how gun violence effects El Salvador and it includes a possible solution as to how to lessen the overwhelming issue that plagues the country

Inhibition of cytochrome c oxidase activity in rat cerebral cortex and human skeletal muscle by d-2-hydroxyglutaric acid in vitro

Abstractl-2-Hydroxyglutaric (LGA) and d-2-hydroxyglutaric (DGA) acids are the characteristic metabolites accumulating in the neurometabolic disorders known as l-2-hydroxyglutaric aciduria and d-2-hydroxyglutaric aciduria, respectively. Although these disorders are predominantly characterized by severe neurological symptoms, the neurotoxic mechanisms of brain damage are virtually unknown. In this study we have evaluated the role of LGA and DGA at concentrations ranging from 0.01 to 5.0 mM on various parameters of energy metabolism in cerebral cortex slices and homogenates of 30-day-old Wistar rats, namely glucose uptake, CO2 production and the respiratory chain enzyme activities of complexes I to IV. DGA significantly decreased glucose utilization (2.5 and 5.0 mM) by brain homogenates and CO2 production (5 mM) by brain homogenates and slices, whereas LGA had no effect on either measurement. Furthermore, DGA significantly inhibited cytochrome c oxidase activity (complex IV) (EC 1.9.3.1) in a dose-dependent manner (35–95%) at doses as low as 0.5 mM, without compromising the other respiratory chain enzyme activities. In contrast, LGA did not interfere with these activities. Our results suggest that the strong inhibition of cytochrome c oxidase activity by increased levels of DGA could be related to the neurodegeneration of patients affected by d-2-hydroxyglutaric aciduria

Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

New Insights toward the Acute Non-Thyroidal Illness Syndrome

The non-thyroidal illness syndrome (NTIS) refers to changes in serum thyroid hormone levels observed in critically ill patients in the absence of hypothalamic–pituitary–thyroid primary dysfunction. Affected individuals have low T3, elevated rT3, and inappropriately normal TSH levels. The pathophysiological mechanisms are poorly understood but the acute and chronic changes in pituitary–thyroid function are probably the consequence of the action of multiple factors. The early phase seems to reflect changes occurring primarily in the peripheral thyroid hormone metabolism, best seen in humans since 80–90% of the circulating T3 are derived from the pro-hormone T4. The conversion of T4 to T3 is catalyzed by type 1 (D1) and type 2 (D2) deiodinases via outer-ring deiodination. In contrast, type 3 deiodinase (D3) catalyzes the inactivation of both T4 and T3. Over the last decades, several studies have attempted to elucidate the mechanisms underlying the changes on circulating thyroid hormones in NTIS. Increased inflammatory cytokines, which occurs in response to virtually any illness, has long been speculated to play a role in derangements of deiodinase expression. On the other hand, oxidative stress due to augmented reactive oxygen species (ROS) generation is characteristic of many diseases that are associated with NTIS. Changes in the intracellular redox state may disrupt deiodinase function by independent mechanisms, which might include depletion of the as yet unidentified endogenous thiol cofactor. Here we aim to present an updated picture of the advances in understanding the mechanisms that result in the fall of thyroid hormone levels in the acute phase of NTIS

Ethnozoology in the mountains. What does the cognitive salience of wild animals tell us?

In recent times, ethnobiology has revived interest in cognitive aspects of humans' communities. A concept commonly used in this area is cognitive salience. In this paper we assess the wild animal salience meaning for the rural people from an area of the mountain range of the Cordoba province (Argentina). We also analyzed the relationship of cultural and ecological factors over wild animal domain salience. The values of cognitive salience, perception and cultural value were obtained by means of free lists to 16 collaborators, while semistructured interviews were used to inquire about local ecological knowledge and ease of observation about wild animals. The interdependence between the five variables elaborated was analyzed through a Principal Components Regression. The results show a qualitative relationship between Cognitive Salience and Cultural Value and a significant correlation between Cognitive Salience and Local Ecological Knowledge. Ease of Observation did not correlate with Cognitive Salience, but show a significant relationship with the Perceived Abundance. The results suggest a complex network of factors that are modeling the cognitive salience and local perceptions over wild animals. In our findings, highlight the Cultural Value given to harmful animals which reflects an increasing pattern in the region, the conflict between rural people and wild animals. In turn a mutual influences and causal feedback loops between cognitive salience and an ecological factor, the Perceived abundance, is proposed. Investigations over cognition and about how people perceived nature can give us an idea of how they act in it, a compelling factor when it comes to cultural and biological conservation issues.Fil: Wajner, Matias. No especifíca;Fil: Tamburini, Daniela Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Zamudio, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin

Conocimiento ecológico local sobre animales silvesetres y sus redes de interacción etnobiológicas, por parte de pobladores rurales de los alrededores de la Cuchila Nevada, Sierras Grandes, Córdoba.

Tesina (Grado en Ciencias Biológicas)--Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Lugar de Trabajo: Instituto Multidisciplinario de Biología Vegetal-IMBIV-U.N.C. Laboratorio de Interacciones Ecológicas y Conservación - 2018. 85 h. con Anexos. grafs.; tabls. Contiene Referencia Bibliográfica.El presente estudio se realizó en la Cuchilla Nevada (Sierras Grandes-Córdoba) desde una perspectiva etnozoológica, la cual es considerada el área que se concentra en las prácticas y representaciones humanas inherentes al mundo animal. El objetivo general fue documentar y analizar los conocimientos ecológicos locales y percepciones de los pobladores sobre los animales silvestres y construir redes de interacción etbnobiológicas en base a dichos saberes con la finalidad de dar posibles explicaciones de por qué hay animales que se destacan más y otros menos dentro de la cognición humana. Para ello primero se obtuvo la Prominencia Cognitiva, que es un parámetro que muestra qué lugar ocupan los animales mencionados de un listado libre en la psiquis de un conjunto de personas. Luego se obtuvieron los parámetros Facilidad de Observación, Importancia Cultural, y finalmente se confeccionaron Redes de Interacciones Etnobiológicas como modelo explicativo del Conocimiento Ecológico Local. Los datos se obtuvieron principalmente mediante entrevistas semi-estructuradas y listados libres a un total de 16 colaboradores. Estas fueron complementadas con entrevistas estructuradas para una sub-muestra de los colaboradores entrevistados y consulta a especialistas del ámbito académico. Una vez obtenido los datos se utilizó la fórmula propuesta por Urmas Sutrop para analizar Prominencia Cognitiva e Importancia Cultural, y se diseñaron métodos y fórmulas para analizar Facilidad de Observación y las Redes de Interacción Etnobiológicas. A partir de la lista de animales mencionados, y valorados de acuerdo a la prominencia cognitiva, se seleccionaron un total de 15 etnoespecies contemplando a las 5 de alta, 5 de media, y 5 de baja Prominencia Cognitiva. Luego se correlacionaron las variables a partir de correlaciones no paramétricas (Sperman). Los pobladores de la Cuchilla Nevada mencionaron un total de 45 animales silvestres de los cuales los Mamíferos ocupan un lugar prioritario, a pesar de que aves fue el taxón con mayor número de menciones. Se encontraron correlaciones positivas entre Prominencia Cognitiva y Cantidad de interacciones que presentan los animales dentro de una red (r=0,57; p=0,03), y también entre Prominencia Cognitiva y Facilidad de Observación (r=0,77; p=0,0041). Además se observó un vínculo entre Importancia Cultural y Prominencia cognitiva, indicando que los animales que se encuentran más alto en el listado son los más importantes culturalmente. A modo de conclusión se sugiere que el lugar que ocupa un determinado animal en la psiquis de los pobladores de la Cuchilla Nevada es determinado tanto por la importancia cultural que posee dicho animal, como por su facilidad de observación, y que estos atributos a su vez modelan el conocimiento ecológico (representado por interacciones etnobiológicas) que se tiene sobre los mismos

Causas e preditores de mortalidade em pacientes que internam com ou por insuficiência cardíaca em hospital terciário no Brasil

Objetivo: Comparar, em hospital brasileiro, preditores e causas de morte em pacientes que internam por insuficiência cardíaca aguda descompensada (ICAD) versus pacientes com insuficiência cardíaca (IC) que internam por outros motivos (ICND). Método: Coorte prospectiva de pacientes internados com diagnóstico de IC identificado pelo escore de Charlson, com acompanhamento mediano de 46 meses. Resultados: Avaliamos 2.056 pacientes (17,6% óbitos no hospital e 38,7% óbitos após alta). Houve mais óbitos por causa cardiovascular no grupo ICAD (principalmente IC) e por doença não cardiovascular no grupo ICND. Não houve diferença de sobrevida pós-alta entre os grupos. O escore de Charlson e a idade foram preditores independentes de morte comum tanto no ambiente hospitalar como extra-hospitalar. Conclusão: A identificação de pacientes de alto risco, independente do motivo da internação, é fundamental para se criar modelos prognósticos e assistenciais. Sugere-se pesquisar causas de óbito e populações variadas para diminuir sua morbimortalidade

Omedelbart omhändertagande av djur utanför kontorstid

Immediately taking charge of animals is one legal measure of animal protection that is regulated in the Swedish animal welfare act (2018:1192), from hereon called the AW act. The same legal measure, which regards dogs only, is regulated in the law of supervision of dogs and cats (2007:1150), from hereon called the law of supervision, to protect society from harm or considerable inconvenience. Within regular office hours, it’s the Swedish County Administration Board (CAB) that’s in charge of ensuring that the animal welfare legislation is complied with. Both the CAB and the Swedish police can immediately take charge of animals for animal protection purposes. However, only the Swedish police can immediately take charge of dogs for other reasons than animal welfare, such as protection of citizens or property. Outside of the CABs’ office hours, the Swedish police have legal authority to immediately take charge of animals they encounter during police work. The aim of this study was to examine the occurrence of authority decisions being made of immediately taking charge of animals outside office hours and to map out where in Sweden this happens. The aim was also to investigate what challenges the CABs and the Swedish police experience with immediately taking charge of animals outside of office hours and how they perceive its effect on the animals. Both the AW act and the law of supervision were considered. This study was done in two parts. The first consisted of gathering statistics from the Swedish police where the data was related to cases where animals have been immediately taken charged of between the years 2020 and 2023. The second part involved semi-structured interviews with a total of eight respondents from selected CABs, police regions and the Swedish police’s national animal protection group. All interviews were performed digitally except one that took place over the telephone. The results showed that the Swedish police made decisions on taking charge of animals most often in Stockholm with 25,8%, Skåne with 14,7% and Västra Götaland with 13,2%. Most of the decisions were based on the AW act with 82,6%, while only 3,3% were based on the law of supervision, while the remaining 14,1% were never subordinated to the CABs. The majority of animals which were included in these decisions were in the counties Skåne with 27,7%, Stockholm with 21,1% and Västra Götaland with 11,8%. Of the decisions, 41,0% were made within office hours, while remaining 59,0% were made outside of office hours. The interviews revealed that the police and CABs shared both common and diverse experiences of the challenges and what impact taking charge has on animals. The important, common ground they share were the application of legislation, deficiencies in case management and communication, and practical challenges. The respondents perceived that the animals being immediately taken charged of are affected to a certain degree, but there’s need of further study to what extent and how