Genetic variants in triglyceride metabolism genes among individuals with hypertriglyceridemia in Colombia.

Background: The genetic substrate of severe hypertriglyceridemia (sHTG) in Latin America is insufficiently understood.

Objective: To identify genetic variants in genes related to triglyceride (TG) metabolism among adults with sHTG from Colombia.

Methods: In individuals with plasma TG≥880 mg/dL at least once in their lifetime, we amplified and sequenced all exons and intron/exon boundaries of the genes LPL, APOC2, APOA5, GPIHBP1 and LMF1.

Large-pore connexin hemichannels function like molecule transporters independent of ion conduction.

Connexin hemichannels were identified as the first members of the eukaryotic large-pore channel family that mediate permeation of both atomic ions and small molecules between the intracellular and extracellular environments. The conventional view is that their pore is a large passive conduit through which both ions and molecules diffuse in a similar manner. In stark contrast to this notion, we demonstrate that the permeation of ions and of molecules in connexin hemichannels can be uncoupled and differentially regulated.

Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries.

S-nitrosylation of Cx43 gap junction channels critically regulates communication between smooth muscle cells and endothelial cells. This posttranslational modification also induces the opening of undocked Cx43 hemichannels. However, its specific impact on vasomotor regulation remains unclear.

Two putative pore-forming proteins, GRA47 and GRA72, influence small molecule permeability of the parasitophorous vacuole.

Unlabelled: , a medically important intracellular parasite, uses GRA proteins secreted from dense granule organelles to mediate nutrient flux across the parasitophorous vacuole membrane (PVM). GRA17 and GRA23 are known pore-forming proteins on the PVM involved in this process, but the roles of additional proteins have remained largely uncharacterized. We recently identified as synthetically lethal with .

GRA47 and GRA72 are pore-forming proteins that influence small molecule permeability of the parasitophorous vacuole.

, a medically important intracellular parasite, uses GRA proteins, secreted from dense granule organelles, to mediate nutrient flux across the parasitophorous vacuole membrane (PVM). GRA17 and GRA23 are known pore-forming proteins on the PVM involved in this process, but the roles of additional proteins have remained largely uncharacterized. We recently identified as synthetically lethal with .

Medium-chain fatty acids modify macrophage expression of metabolic and inflammatory genes in a PPAR β/δ-dependent manner.

There is great interest on medium chain fatty acids (MCFA) for cardiovascular health. We explored the effects of MCFA on the expression of lipid metabolism and inflammatory genes in macrophages, and the extent to which they were mediated by the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR β/δ). J774A.

Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.

Microcirculation homeostasis depends on several channels permeable to ions and/or small molecules that facilitate the regulation of the vasomotor tone, hyperpermeability, the blood-brain barrier, and the neurovascular coupling function. Connexin (Cxs) and Pannexin (Panxs) large-pore channel proteins are implicated in several aspects of vascular physiology. The permeation of ions (i.

Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador.

Rare pathogenic variants in the LMF1 gene, which encodes lipase maturation factor 1, are a minor cause of familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia. In this report we present three adult patients, all of them born and raised in Quito, Ecuador, with severe hypertriglyceridemia secondary to biallelic LMF1 variants. In two of the three cases (patients 1 and 3), the presentation was acute pancreatitis secondary to plasma triglycerides well above 10 mmol/L.

Social inequalities shape diet composition among urban Colombians: The Colombian Nutritional Profiles cross-sectional study.

Objective: To explore the influence of socioeconomic position on habitual dietary intake in Colombian cities.

Design: We conducted a cross-sectional, population-based study in five Colombian cities. Dietary intake was assessed with a 157-item semi-quantitative food frequency questionnaire previously developed for the Colombian population.

Poor performance of anti-mitochondrial antibodies for the diagnosis of primary biliary cholangitis in female Colombian patients: A single-center study.

Background: Primary biliary cholangitis (PBC) is a serious disease that causes significant morbidity. PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis. The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations.

A method for assessing ionic and molecular permeation in connexin hemichannels.

Connexin hemichannels are permeable to both atomic ions and small molecules. Yet, they have different selectivity for ions and signaling molecules critical for biological functions. Activity of connexin hemichannels in living cells is commonly evaluated by methods that include electrophysiology and fluorescence-based approaches.

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile.

Background: Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time.

Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.

Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca] of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O ) formation, and endothelial cell [Ca] were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells.

ATP and large signaling metabolites flux through caspase-activated Pannexin 1 channels.

Pannexin 1 (Panx1) is a membrane channel implicated in numerous physiological and pathophysiological processes via its ability to support release of ATP and other cellular metabolites for local intercellular signaling. However, to date, there has been no direct demonstration of large molecule permeation via the Panx1 channel itself, and thus the permselectivity of Panx1 for different molecules remains unknown. To address this, we expressed, purified, and reconstituted Panx1 into proteoliposomes and demonstrated that channel activation by caspase cleavage yields a dye-permeable pore that favors flux of anionic, large-molecule permeants (up to ~1 kDa).

Eating disorders in adolescents: role of the pediatrician. Recommendations of the Adolescence Branch of the Chilean Society of Pediatrics.

Eating disorders (ED) have become relevant in Chilean pediatrics. Their treatment must be prefe rably carried out by multidisciplinary teams with specialty or a high degree of training in the pro blem. However, general pediatricians have a fundamental role both in the prevention and in the early detection of these pathologies.

[Eating disorders in adolescents. A comprehensive approach].

Eating disorders (ED) are very serious diseases that usually begin in adolescence and have, in general, been increasing in developing countries. In the country, there are currently several fac tors that hinder their prevention, detection, and treatment, where the lack of training of health professionals in this emerging issue appears as an important one. The purpose of this article is to contribute to the knowledge that pediatricians have about ED in adolescence, through an updated review of the literature on the subject.

A novel voltage-clamp/dye uptake assay reveals saturable transport of molecules through CALHM1 and connexin channels.

Large-pore channels permeable to small molecules such as ATP, in addition to atomic ions, are emerging as important regulators in health and disease. Nonetheless, their mechanisms of molecular permeation and selectivity remain mostly unexplored. Combining fluorescence microscopy and electrophysiology, we developed a novel technique that allows kinetic analysis of molecular permeation through connexin and CALHM1 channels in Xenopus oocytes rendered translucent.

[Familial chylomicronemia].

Familial chylomicronemia is a disease in which a genetic mutation affects the ability of the organism to metabolize triglycerides bound to lipoproteins, causing extremely high plasma triglycerides and associated consequences. The most frequent complication is acute pancreatitis, which may lead to multiorganic failure or pancreatic insufficiency. Familial chylomicronemia also exerts a profound negative impact on quality of life, social relationships and professional development.

Function of P2X4 Receptors Is Directly Modulated by a 1:1 Stoichiometric Interaction With 5-HTA Receptors.

Interacting receptors at the neuronal plasma membrane represent an additional regulatory mode for intracellular transduction pathways. P2X4 receptor triggers fast neurotransmission responses a transient increase in intracellular Ca levels. It has been proposed that the P2X4 receptor interacts with the 5-HTA receptor in hippocampal neurons, but their binding stoichiometry and the role of P2X4 receptor activation by ATP on this crosstalking system remains unknown.

Taking a close look at a large-pore channel.

The structure of pannexin 1, a channel protein with a large pore, has been determined for the first time.

[Changes in prescriptions and antibiotic consumption after the implementation of recommendations for use: experience in a university hospital].

Background: Nowadays about half of antibiotic prescriptions are inadequate, increasing bacterial resistance. Both cephalosporins and fluoroquinolones are associated with this phenomenon: increase of β-lactamase producing bacteria and Clostridioides difficile infections, which is why regulatory agencies seek to rationalize their use.

Aim: To evaluate the effect of use recommendations on the proportion of inadequate prescriptions of ceftriaxone and fluoroquinolones.

Impact of a Formulation Containing Unusual Polyunsaturated Fatty Acids, Trace Elements, Polyphenols and Plant Sterols on Insulin Resistance and Associated Disturbances.

Introduction: To evaluate the effect of a lipid-based formulation containing unusual polyunsaturated fatty acids, trace elements, polyphenols and plant sterols on insulin resistance and its associated disturbances among adults at risk of diabetes.

Methods: This was an 8-week, three-arm, open-label randomized clinical trial. We studied individuals aged ≥ 18 years old with diabetes risk given by a body mass index ≥ 25 kg/m or a FinnRisc score ≥ 13/20.

CGRP signalling inhibits NO production through pannexin-1 channel activation in endothelial cells.

Blood flow distribution relies on precise coordinated control of vasomotor tone of resistance arteries by complex signalling interactions between perivascular nerves and endothelial cells. Sympathetic nerves are vasoconstrictors, whereas endothelium-dependent NO production provides a vasodilator component. In addition, resistance vessels are also innervated by sensory nerves, which are activated during inflammation and cause vasodilation by the release of calcitonin gene-related peptide (CGRP).

Laboratory exposure to Coccidioides: lessons learnt in a non-endemic country.

Coccidioides is a primary pathogenic fungus, which infects humans through highly infectious arthroconidia, causing substantial morbidity including life-threatening disseminated infections. Due to the low infectious dose, laboratory personnel might become infected during diagnostic procedures. Accordingly, coccidioidomycosis is reported as the most frequent laboratory-acquired systemic mycosis worldwide.