Effect of epicatechin consumption on the inflammatory pathway and mitochondria morphology in PBMC from a R350P desminopathy patient: A case report.

Desminopathy R350P is a human myopathy that is characterized by the progressive loss of muscle fiber organization. This results in the loss of muscle size, mobility, and strength. In desminopathy, inflammation affects muscle homeostasis and repair, and contributes to progressive muscle deterioration. Mitochondria morphology was also suggested to affect desminopathy progression. Epicatechin (Epi)-a natural compound found in cacao-has been proposed to regulate inflammatory signaling and mitochondria morphology in human and animal models. Hence, we hypothesize chronic Epi consumption to improve inflammatory pathway and mitochondria morphology in the peripheral blood mononuclear cells (PBMCs) of a desminopathy R350P patient. We found that 12 weeks of Epi consumption partially restored TRL4 signaling, indicative of inflammatory signaling and mitochondria morphology in the desminopathy patient. Moreover, Epi consumption improved blood health parameters, including reduced HOMA-IR and IL-6 levels in the desminopathy patient. This indicates that Epi consumption could be a useful tool to slow disease progression in desminopathy patients.

Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects

Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT.

Antecedentes: Las especies reactivas de oxígeno (ROS) regulan el metabolismo de la glucosa (GM) en el músculo esquelético al mejorar la translocación de GLUT4. La suplementación con antioxidantes podría bloquear este efecto fisiológico, alterando la señalización de la glucosa durante el ejercicio. Sin embargo, existe evidencia limitada en humanos sobre si la ingesta de antioxidantes afecta el GM. Por lo tanto, nuestro objetivo fue determinar el efecto de un cóctel de antioxidantes (AOC) en el GM en reposo y durante desafíos metabólicos. Métodos: Sujetos sanos (sexo masculino; n= 10) recibieron suplementos de AOC (1.000 mg de vitamina C, 600 UI de vitamina E y 600 mg de ácido α-lipoico) o placebo (2.000 mg de talco) previo a dos pruebas realizadas con 7 días de diferencia. Prueba 1: AOC 120 y 90 minutos antes de una serie de ejercicio de resistencia (EEX) al 60% del consumo máximo de oxígeno (VO2max); prueba 2: AOC 120 y 90 minutos antes de una prueba de tolerancia oral a la glucosa (OGTT; 75 g de glucosa). Se obtuvieron datos de intercambio de gaseoso y muestras de sangre capilar cada 15 minutos durante ambas pruebas. Resultados: la suplementación con AOC aumentó los niveles de glucosa en reposo (p<0,05). Durante la prueba 1 (EEX), el AOC aumentó la oxidación de carbohidratos (CHOox) (p= 0,03), sin efecto en los niveles de glucosa en sangre. Durante la prueba 2 (OGTT), la suplementación con AOC no tuvo un efecto significativo en los parámetros de GM. Conclusión: Una suplementación aguda con AOC aumentó los niveles de glucosa en reposo y la CHOox durante EEX en sujetos sanos, sin efecto sobre el GM durante la OGTT.

Clinical and Endoscopic Characterization of Gastrointestinal Kaposi's Sarcoma in an Institution in Southwestern Colombia between 2011 and 2020

Kaposi's sarcoma is an angioproliferative neoplasm associated with the human herpesvirus 8. According to the clinical characteristics and the degree of immunosuppression, there are four epidemiological forms: classic, endemic, iatrogenic, and epidemic. The latter is associated with acquired immunodeficiency syndrome (AIDS) and 40% GI involvement. There is little epidemiological, clinical, and endoscopic evidence of the disease. This study sought to characterize this condition in a Colombian population and compare the findings with publications from other countries. One hundred thirty-five records of patients who consulted between 2011 and 2020 for Kaposi's sarcoma were reviewed, of which 24 had GI involvement. Epidemiological, clinical, endoscopic, and treatment characteristics were obtained. Twenty-two patients were men. There were 21 patients infected with human immunodeficiency virus (HIV; 87.5%) and 19 receiving antiretroviral therapy (90%); 33.3% had HIV viral load > 100,000 copies/mL. The CD4+ count was <50 cells/µL in 28.6% of cases, between 50 and 100 cells/µL in 19.0%, and between 100 and 200 cells/µL in 14.4%. The rate of infection by other opportunistic infections was 41.7%. There were GI symptoms in 33% of the patients, and the most frequent were hematochezia, abdominal pain, nausea, and diarrhea. Most had concomitant skin lesions (70.8%). GI lesions were located mainly in the oropharynx (41.7%), stomach (20.8%), and colon (16.7%). The most common endoscopic finding was maculopapular erythema. This article provided insight into the local epidemiology of gastrointestinal Kaposi's sarcoma. In contrast to studies in other populations, GI symptoms were more frequent in this one, and there was a difference in endoscopic findings. Studies with larger populations are needed.

El sarcoma de Kaposi es una neoplasia angioproliferativa asociada al virus del herpes humano 8. Según las características clínicas y el grado de inmunosupresión, son cuatro las formas epidemiológicas: clásica, endémica, iatrogénica y epidémica, esta última asociada al síndrome de inmunodeficiencia adquirida (SIDA) y con un 40% de compromiso gastrointestinal. Existe escasa evidencia epidemiológica, clínica y endoscópica de la enfermedad. Este estudio buscó caracterizar esta condición en una población colombiana y contrastar los hallazgos con publicaciones de otros países. Se revisaron 135 registros de pacientes que consultaron entre el 2011 y 2020 por sarcoma de Kaposi, de los cuales 24 tenían compromiso gastrointestinal. Se obtuvieron características epidemiológicas, clínicas, endoscópicas y tratamientos. Veintidós pacientes eran hombres. Hubo 21 pacientes infectados por virus de la inmunodeficiencia humana (VIH; 87,5%) y 19 recibían terapia antirretroviral (90%). El 33,3% tenía carga viral VIH > 100 000 copias/mL. El recuento de CD4+ fue < 50 cel/µL en el 28,6% de los casos, entre 50 y 100 cel/µL en el 19,0%, y entre 100 y 200 cel/µL en el 14,4%. La tasa de infecciones por otros oportunistas fue de 41,7%. Hubo síntomas gastrointestinales en el 33% de los pacientes y los más frecuentes fueron hematoquecia, dolor abdominal, náuseas y diarrea. La mayoría tuvo lesiones cutáneas concomitantes (70,8%). Las lesiones gastrointestinales se localizaron principalmente en la orofaringe (41,7%), estómago (20,8%) y colon (16,7%). El hallazgo endoscópico más común fue eritema maculopapular. Este artículo mostró una visión de la epidemiología local del sarcoma de Kaposi gastrointestinal. En contraste con estudios en otras poblaciones, en este, los síntomas gastrointestinales fueron más frecuentes y hubo diferencia en los hallazgos endoscópicos. Son necesarios estudios con poblaciones más grandes.

Regulation of mitochondrial morphology and cristae architecture by the TLR4 pathway in human skeletal muscle.

In skeletal muscle (SkM), a reduced mitochondrial elongate phenotype is associated with several metabolic disorders like type 2 diabetes mellitus (T2DM). However, the mechanisms contributing to this reduction in mitochondrial elongate phenotype in SkM have not been fully elucidated. It has recently been shown in a SkM cell line that toll-like receptor 4 (TLR4) contributes to the regulation of mitochondrial morphology. However, this has not been investigated in human SkM. Here we found that in human SkM biopsies, TLR4 protein correlated negatively with Opa1 (pro-mitochondrial fusion protein). Moreover, the incubation of human myotubes with LPS reduced mitochondrial size and elongation and induced abnormal mitochondrial cristae, which was prevented with the co-incubation of LPS with TAK242. Finally, T2DM myotubes were found to have reduced mitochondrial elongation and mitochondrial cristae density. Mitochondrial morphology, membrane structure, and insulin-stimulated glucose uptake were restored to healthy levels in T2DM myotubes treated with TAK242. In conclusion, mitochondrial morphology and mitochondrial cristae seem to be regulated by the TLR4 pathway in human SkM. Those mitochondrial alterations might potentially contribute to insulin resistance in the SkM of patients with T2DM.

Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic flux in skeletal muscle cells.

BACKGROUND: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. METHODS: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. RESULTS: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. CONCLUSION: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux.

BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

Mitochondria-SR interaction and mitochondrial fusion/fission in the regulation of skeletal muscle metabolism.

Mitochondria-endoplasmic/sarcoplasmic reticulum (ER/SR) interaction and mitochondrial fusion/fission are critical processes that influence substrate oxidation. This narrative review summarizes the evidence on the effects of substrate availability on mitochondrial-SR interaction and mitochondria fusion/fission dynamics to modulate substrate oxidation in human skeletal muscle. Evidence shows that an increase in mitochondria-SR interaction and mitochondrial fusion are associated with elevated fatty acid oxidation. In contrast, a decrease in mitochondria-SR interaction and an increase in mitochondrial fission are associated with an elevated glycolytic activity. Based on the evidence reviewed, we postulate two hypotheses for the link between mitochondrial dynamics and insulin resistance in human skeletal muscle. First, glucose and fatty acid availability modifies mitochondria-SR interaction and mitochondrial fusion/fission to help the cell to adapt substrate oxidation appropriately. Individuals with an impaired response to these substrate challenges will accumulate lipid species and develop insulin resistance in skeletal muscle. Second, a chronically elevated substrate availability (e.g. overfeeding) increases mitochondrial production of reactive oxygen species and induced mitochondrial fission. This decreases fatty acid oxidation, thus leading to the accumulation of lipid species and insulin resistance in skeletal muscle. Altogether, we propose mitochondrial dynamics as a potential target for disturbances associated with low fatty acid oxidation.

Neither Chia Flour nor Whey Protein Supplementation Further Improves Body Composition or Strength Gains after a Resistance Training Program in Young Subjects with a Habitual High Daily Protein Intake.

The aim of this study was to compare the potential additional effect of chia flour, whey protein, and a placebo juice to resistance training on fat-free mass (FFM) and strength gains in untrained young men. Eighteen healthy, untrained young men underwent an 8-week whole-body resistance training program, comprising three sessions per week. Subjects were randomized into three groups that after each training session consumed: (1) 30 g whey protein concentrate containing 23 g protein (WG), (2) 50 g chia flour containing 20 g protein (CG), or (3) a placebo not containing protein (PG). Strength tests (lower- and upper-limb one repetition maximum (1 RM) tests) and body composition analyses (dual-energy X-ray absorptiometry; DXA) were performed before (PRE) and after (POST) the intervention. Resistance training increased FFM and the 1 RM for each of the strength tests similarly in the three groups. FFM increased by 2.3% in WG (p = 0.04), by 3.6% in CG (p = 0.004), and by 3.0% in PG (p = 0.002)., and 1 RM increased in the different strength tests in the three groups (p < 0.05) with no difference between PG, CG, and WG. In conclusion, neither chia flour nor whey protein supplementation elicited an enhanced effect on FFM and strength gains after an 8-week resistance training program in healthy, untrained young men consuming a habitual high protein mixed diet (>1.2 g/kg/day).

Targeting Mitochondria for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: Polyphenols as a Non-pharmacological Approach.

SCOPE: Nonalcoholic fatty liver disease (NAFLD) has a high and growing prevalence globally. Mitochondria are fundamental in regulating cell energy homeostasis. Nevertheless, mitochondria control mechanisms can be exceeded in this context of energy overload. Damaged mitochondria worsen NAFLD progression. Diet and lifestyle changes are the main recommendations for NAFLD prevention and treatment. Some polyphenols have improved mitochondrial function in different NAFLD and obesity models. OBJECTIVE: The study aims to discuss the potential role of polyphenols as a nonpharmacological approach targeting mitochondria to prevent and treat NAFLD, analyzing the influence of polyphenols' chemical structure, limitations and clinical projections. METHODS: In vivo and in vitro NAFLD models were considered. Study searches were performed using the following keywords: nonalcoholic fatty liver disease, liver steatosis, mitochondria, mitochondrial activity, mitochondrial dynamics, mitochondrial dysfunction, mitochondrial morphology, mitochondrial cristae, fusion, fission, polyphenols, flavonoids, anthocyanins, AND/OR bioactive compounds. CONCLUSION: Polyphenols are a group of diverse bioactive molecules whose bioactive effects are highly determined by their chemical structure. These bioactive compounds could offer an interesting non-pharmacological approach to preventing and treating NAFLD, regulating mitochondrial dynamics and function. Nevertheless, the mitochondria' role in subjects with NAFLD treatment is not fully elucidated. The dosage and bioavailability of these compounds should be addressed when studied.

Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic flux in skeletal muscle cells

BACKGROUND: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia.METHODS: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. RESULTS: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. CONCLUSION: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.

Ursodeoxycholic acid induces sarcopenia associated with decreased protein synthesis and autophagic flux

BACKGROUND: Skeletal muscle generates force and movements and maintains posture. Under pathological conditions, muscle fibers suffer an imbalance in protein synthesis/degradation. This event causes muscle mass loss and decreased strength and muscle function, a syndrome known as sarcopenia. Recently, our laboratory described secondary sarcopenia in a chronic cholestatic liver disease (CCLD) mouse model. Interestingly, the administration of ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is an effective therapy for cholestatic hepatic alterations. However, the effect of UDCA on skeletal muscle mass and functionality has never been evaluated, nor the possible involved mechanisms. METHODS: We assessed the ability of UDCA to generate sarcopenia in C57BL6 mice and develop a sarcopenic-like phenotype in C2C12 myotubes and isolated muscle fibers. In mice, we measured muscle strength by a grip strength test, muscle mass by bioimpedance and mass for specific muscles, and physical function by a treadmill test. We also detected the fiber's diameter and content of sarcomeric proteins. In C2C12 myotubes and/or isolated muscle fibers, we determined the diameter and troponin I level to validate the cellular effect. Moreover, to evaluate possible mechanisms, we detected puromycin incorporation, p70S6K, and 4EBP1 to evaluate protein synthesis and ULK1, LC3 I, and II protein levels to determine autophagic flux. The mitophagosome-like structures were detected by transmission electron microscopy. RESULTS: UDCA induced sarcopenia in healthy mice, evidenced by decreased strength, muscle mass, and physical function, with a decline in the fiber's diameter and the troponin I protein levels. In the C2C12 myotubes, we observed that UDCA caused a reduction in the diameter and content of MHC, troponin I, puromycin incorporation, and phosphorylated forms of p70S6K and 4EBP1. Further, we detected increased levels of phosphorylated ULK1, the LC3II/LC3I ratio, and the number of mitophagosome-like structures. These data suggest that UDCA induces a sarcopenic-like phenotype with decreased protein synthesis and autophagic flux. CONCLUSIONS: Our results indicate that UDCA induces sarcopenia in mice and sarcopenic-like features in C2C12 myotubes and/or isolated muscle fibers concomitantly with decreased protein synthesis and alterations in autophagic flux.

Prevalencia de Helicobacter pylori en pacientes llevados a endoscopia de vías digestivas altas en un hospital de referencia en Cali, Colombia, en 2020 / Prevalence of Helicobacter pylori in patients undergoing upper digestive tract endoscopy at a referral hospital in Cali, Colombia, in 2020

Resumen Introducción: la infección por Helicobacter pylori tiene una alta prevalencia y distribución a nivel mundial. Por su asociación con el desarrollo de adenocarcinoma gástrico, las actualizaciones sobre su prevalencia son de interés para el médico internista o gastroenterólogo, así como para la generación de políticas públicas. Este estudio midió la prevalencia de H. pylori y evaluó su asociación con hallazgos endoscópicos e histopatológicos en adultos con indicación de endoscopia de vías digestivas altas (EVDA). Metodología: estudio de cohorte analítica para describir la prevalencia de H. pylori y evaluar factores de riesgo asociados a esta infección en pacientes adultos sometidos a EVDA ambulatoria por cualquier indicación médica en la unidad de endoscopia de un hospital universitario de cuarto nivel de complejidad entre junio y diciembre de 2020. Se describen hallazgos endoscópicos, histopatológicos y la prevalencia de H. pylori. Para explorar los factores de riesgo se usó la prueba chi cuadrado (χ2) para evaluar diferencias en las proporciones y las pruebas t de Student y U de Mann-Whitney para las variables continuas según su distribución. Resultados: 613 pacientes cumplieron los criterios de selección y fueron incluidos en el análisis. La indicación más frecuente de EVDA fue dispepsia. La prevalencia de H. pylori fue de 38,5% (intervalo de confianza [IC] 95%: 34,7%-42,4%). Conclusión: H. pylori es un tema de gran interés en las patologías gastrointestinales. La búsqueda endoscópica debe ser en el antro y cuerpo. Su presencia fue mayor en pacientes con esófago normal, gastritis nodular folicular, úlcera duodenal e inflamación aguda al estudio histológico. Se requieren más estudios que complementen el comportamiento epidemiológico local.

Abstract Introduction: Helicobacter pylori infection has a high prevalence and distribution worldwide. Due to its association with the development of gastric adenocarcinoma, updates on its prevalence are of interest to the internist or gastroenterologist and policymaking. This study measured the prevalence of H. pylori and evaluated its association with endoscopic and histopathological findings in adults with an indication for upper GI endoscopy (EGD). Materials and methods: This analytical cohort study describes the prevalence of H. pylori and assesses risk factors associated with this infection in adult patients undergoing outpatient EGD for any medical indication in the endoscopy unit of a quaternary care university hospital between June and December 2020. Endoscopic and histopathological findings and the prevalence of H. pylori are described. To explore the risk factors, the chi-square (χ2) test was used to evaluate differences in proportions and the Student's t and Mann-Whitney U tests for continuous variables according to their distribution. Results: 613 patients met the selection criteria and were included in the analysis. The most frequent indication for EGD was dyspepsia. The prevalence of H. pylori was 38.5% (95% confidence interval [CI]: 34.7-42.4%). Conclusion: H. pylori is a topic of great interest in gastrointestinal pathologies. The endoscopic search should take place in the antrum and body. Its presence was most common in patients with a normal esophagus, follicular nodular gastritis, duodenal ulcer, and acute inflammation upon the histological study. More studies are required to complement the local epidemiological behavior.

Concurrent training and interindividual response in women with a high number of metabolic syndrome risk factors.

The non-responders (NRs) after exercise training have been poorly studied in populations with morbid obesity. The purpose of this study was to determine the NR prevalence after 20 weeks of concurrent training of morbidly obese women with a high or low number of metabolic syndrome (MetS) risk factors. Twenty-eight women with morbid obesity participated in an exercise training intervention and were allocated into two groups distributed based on a high (≥3, n = 11) or low number (<3, n = 17) of MetS risk factors. The main outcomes were waist circumference (WC), fasting plasma glucose (FPG), high-density lipids (HDL-c), triglycerides (Tg), and systolic (SBP) and diastolic (DBP) blood pressure, and secondary outcomes were body composition, anthropometric and physical fitness, determined before and after 20 weeks of concurrent training. NRs were defined as previously used technical error cut-off points for the MetS outcomes. Significantly different (all p < 0.05) prevalences of NRs between the H-MetS vs. L-MetS groups (respectively) in WC (NRs 18.2 % vs. 41.1 %, p < 0.0001), SBP (NRs 72.7 % vs. 47.0 %, p = 0.022), DBP (NRs 54.5 % vs. 76.4 %, p < 0.0001), FPG (NRs 100% vs. 64.8 %, p < 0.0001), and HDL-c (NRs 90.9 % vs. 64.7 %, p = 0.012) were observed. In addition, the H-MetS group evidenced significant changes on ΔSBP (-10.2 ± 11.4 mmHg), ΔFPG (-5.8 ± 8.2 mg/dl), ΔHDL-c (+4.0 ± 5.9 mg/dl), and ΔTg (-8.8 ± 33.8 mg/dl), all p < 0.05. The L-MetS group only showed significant changes in ΔWC (-3.8 ± 5.0 cm, p = 0.009). Comparing H-MetS vs. L-MetS groups, significant differences were observed in ∆FPG (-5.8 ± 8.2 vs. +0.3 ± 3.2 mg/dl, p = 0.027), but not in other MetS outcomes. In conclusion, 20 weeks of concurrent training promotes greater beneficial effects in morbidly obese patients with a high number of MetS risk factors. However, the NR prevalence for improving MetS outcomes was significantly superior in these more-diseased groups in SBP, FPG, and HDL-c, independent of their major training-induced effects.

Sedación administrada por médicos generales para procedimientos endoscópicos de baja complejidad: experiencia en una unidad de endoscopia de una clínica de alta complejidad en Cali / Sedation Administered by General Practitioners for Low Complexity Endoscopic Procedures: Experience in an Endoscopy Unit of a Tertiary Referral Hospital in Cali

Resumen Objetivos: en Colombia se ha venido implementando la sedación por médicos no anestesiólogos para procedimientos endoscópicos fuera del quirófano. Se describió la experiencia en la unidad de gastroenterología de una clínica de alto nivel de atención en Cali, Colombia. Materiales y métodos: estudio observacional, de tipo cohorte analítica para describir la frecuencia y el tipo de eventos adversos asociados a los procedimientos de sedación por médicos generales, y evaluar los factores asociados a su ocurrencia en pacientes que acudieron a la unidad de endoscopia de la Fundación Valle del Lili para la realización de estudios endoscópicos bajo sedación intravenosa que, por ser de bajo riesgo, fue aplicada por un médico no anestesiólogo entre noviembre de 2018 y junio de 2019. Se realizó análisis descriptivo, se calcularon mediana y rango intercuartílico para las variables numéricas, y frecuencias para las variables cualitativas. Resultados: se incluyeron 1506 participantes, 59,4 % ASA I y 40,6 % ASA II. En promedio, la dosis inicial de propofol fue de 60 mg y la dosis total, de 140 mg. Se registraron eventos adversos no serios en 46 pacientes (3,05 %) y el más común fue la desaturación transitoria (80,4 %). Ningún paciente presentó eventos adversos serios. El puntaje inicial promedio de la escala de Aldrete fue 8, mientras que al alta el puntaje promedio fue de 10. Conclusiones: la sedación para procedimientos endoscópicos dada por médicos no anestesiólogos es segura, siempre y cuando sea realizado por personal entrenado que realice una adecuada valoración de los antecedentes (cardiovasculares, gastrointestinales y neurológicos) y factores de riesgo del paciente dentro del marco de los lineamientos institucionales vigentes.

Abstract Objectives: in Colombia, sedation by non-anesthesiologists for endoscopic procedures outside the operating room has been implemented. A description of an experience in the gastroenterology unit of a tertiary referral hospital in Cali, Colombia, was conducted. Materials and methods: an analytical cohort observational study to describe the frequency and type of adverse events associated with sedation procedures performed by general practitioners and evaluate the factors related to their occurrence in patients who attended the endoscopy unit of Fundación Valle del Lili for endoscopic studies under intravenous sedation. Between November 2018 and June 2019, non-anesthesiologist physicians performed this procedure due to the minimal risk implied. A descriptive analysis was completed, and the median and interquartile range were calculated for numerical variables and frequencies for qualitative variables. Results: There were 1506 participants, 59.4% ASA I and 40.6% ASA II in this study. On average, the starting dose of propofol was 60 mg, and the total dose was 140 mg. Forty-six patients (3.05%) reported non-severe adverse events; the most common occurrence was transient desaturation (80.4%). No patients experienced severe adverse events. The average initial Aldrete scale score was 8, while at discharge, the average score was 10. Conclusions: sedation for endoscopic procedures performed by non-anesthesiologists is safe provided that it is performed by trained personnel conducting a correct assessment of the patient's (cardiovascular, gastrointestinal, and neurological) history and risk factors within the framework of the current institutional guidelines.

Severe COVID-19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans.

An interaction between mitochondrial dynamics, physical activity levels, and COVID-19 severity has been previously hypothesized. However, this has not been tested. We aimed to compare mitochondrial morphology and cristae density of PBMCs between subjects with non-severe COVID-19, subjects with severe COVID-19, and healthy controls. Additionally, we compared the level of moderate-vigorous physical activity (MVPA) and sitting time between groups. Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images and western blot of protein that regulate mitochondrial dynamics. The International Physical Activity Questionnaire (IPAQ; short version) was used to estimate the level of MVPA and the sitting time The patients who develop severe COVID-19 (COVID-19++) not present alterations of mitochondrial size neither mitochondrial density in comparison to non-severe patients COVID-19 (COVID-19) and control subjects (CTRL). However, compared to CTRL, COVID-19 and COVID-19++ groups have lower mitochondrial cristae length, a higher proportion of abnormal mitochondrial cristae. The COVID-19++ group has lower number (trend) and length of mitochondrial cristae in comparison to COVID-19 group. COVID-19, but not COVID-19++ group had lower Opa 1, Mfn 2 and SDHB (Complex II) proteins than CTRL group. Besides, COVID-19++ group has a higher time sitting. Our results show that low mitochondrial cristae density, potentially due to physical inactivity, is associated with COVID-19 severity.

Effect of Epicatechin on Skeletal Muscle.

Loss of skeletal muscle (SkM) quality is associated with different clinical conditions such as aging, diabetes, obesity, cancer, and heart failure. Nutritional research has focused on identifying naturally occurring molecules that mitigate the loss of SkM quality induced by pathology or syndrome. In this context, although few human studies have been conducted, epicatechin (Epi) is a prime candidate that may positively affect SkM quality by its potential ability to mitigate muscle mass loss. This seems to be a consequence of its antioxidant and anti-inflammatory properties and its stimulation of mitochondrial biogenesis to increase myogenic differentiation, as well as its modulation of key proteins involved in SkM structure, function, metabolism, and growth. In conclusion, the Epi could prevent, mitigate, delay, and even treat muscle-related disorders caused by aging and diseases. However, studies in humans are needed.

The fasting-feeding metabolic transition regulates mitochondrial dynamics.

In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen-derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting-substrate in vitro. In murine mononuclear-cells, we confirmed that mitochondria-ER interactions are regulated in the fasted-fed transition and we further highlight mitochondria-ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.

Características clínicas de pacientes con pancreatitis aguda atendidos en un hospital de alta complejidad en Cali / Clinical characteristics of patients with acute pancreatitis treated in a tertiary referral hospital in Cali

Resumen Introducción: la pancreatitis aguda (PA) es una enfermedad de alta complejidad clínica y, de acuerdo con su gravedad, puede tener una elevada morbimortalidad con altos costos para el sistema de salud, especialmente a nivel intrahospitalario. Materiales y métodos: se desarrolló un estudio descriptivo basado en historias clínicas de un hospital universitario de alta complejidad. Se revisaron las historias con diagnóstico CIE 10 de pancreatitis aguda entre enero de 2011 y diciembre de 2018. Se incluyeron todos los pacientes mayores de 18 años, de ambos sexos, con diagnóstico de PA por cumplimiento de al menos 2 de los criterios de Atlanta de 2012. Resultados: se revisaron 1353 historias clínicas, de las cuales 386 cumplieron criterios para PA. Entre ellas se identificaron 205 mujeres (53 %) y 181 hombres (47 %), y la prevalencia de comorbilidades fue inferior al 10 %. El 38 % de los casos de pancreatitis ocurrieron en personas entre los 50 y 70 años de edad. Con respecto a la etiología de la PA, el origen biliar fue el de mayor frecuencia, con 200 casos del total (52 %); seguido de idiopático (19,7 %) y poscolangiopancreatografía retrógrada endoscópica (CPRE), que ocurrió en 33 pacientes (8,5 %). Conclusiones: la PA es una entidad frecuente que afecta a adultos de todas las edades y genera una cantidad importante de consultas en urgencias. En Colombia, los datos previos apuntaban a pacientes con pancreatitis graves y no se tenía conocimiento del comportamiento sociodemográfico y clínico de las pancreatitis agudas en urgencias.

Abstract Introduction: Acute pancreatitis (AP) is a disease with a high degree of clinical complexity, and depending on its severity, it can have high morbidity and mortality rates, resulting in substantial health-care costs, particularly at the hospital level. Materials and methods: A descriptive study was developed based on the medical records of a tertiary referral university hospital. The records that included an ICD 10 diagnosis of acute pancreatitis between January 2011 and December 2018 were reviewed. All patients over the age of 18, of both sexes, with an AP diagnosis who met at least two of the 2012 Atlanta criteria were included in the study. Results: 1 353 records were reviewed, of which 386 met the criteria for AP. There were 205 women (53%) and 181 males (47%) among them, and comorbidities were found in less than 10% of the participants. 38% of cases of pancreatitis occurred in people between 50 and 70 years of age. Regarding the etiology of AP, biliary origin was the most frequent with 200 cases (52%), followed by idiopathic (19.7%) and post-endoscopic retrograde cholangiopancreatography (ERCP) in 33 patients (8.5%). Conclusions: AP is a common condition that affects adults of all ages and results in a high number of emergency room visits. Previous data in Colombia was only available for individuals with severe pancreatitis, and nothing was known about the sociodemographic and clinical characteristics of acute pancreatitis in the emergency room.

Low abundance of Mfn2 protein correlates with reduced mitochondria-SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images.

The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondria-sarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria-SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed "by-hand," thus potentially leading to between-rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial-SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial-SR juxtaposition, mitochondrial morphology, MCD (stereological-method), and SM quality (cross-sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2-HA; n = 6) and low abundance (Mfn2-LA; n = 6) of Mfn2 protein. The mitochondria-SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2-HA and Mfn2-LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2-LA group showed lower mitochondria-SR interaction, MCD, and VO2max . In conclusion, mitochondrial-SR juxtaposition measurement depends on the experience of the rater, and Mfn2 protein seems to play a role in the metabolic control of human men SM, by regulating the mitochondria-SR interaction.

Long-term effects of young-adult methamphetamine on dorsal raphe serotonin systems in mice: Role of brain-derived neurotrophic factor.

To assess the long-term effects of chronic adolescent methamphetamine (METH) treatment on the serotonin system in the brain, we used serotonin-1A receptor (5-HT1A) and serotonin transporter (SERT) autoradiography, and quantitative tryptophan-hydroxylase 2 (TPH2) immunohistochemistry in the raphe nuclei of mice. Because of the modulatory role of brain-derived neurotrophic factor (BDNF) on the serotonin system and the effects of METH, we included both BDNF heterozygous (HET) mice and wildtype (WT) controls. Male and female mice of both genotypes were treated with an escalating METH dose regimen from the age of 6-9 weeks. At least two weeks later, acute locomotor hyperactivity induced by a 5 mg/kg D-amphetamine challenge was significantly enhanced in METH-pretreated mice, showing long-term sensitisation. METH pretreatment caused a small, but significant decrease of 5-HT1A receptor binding in the dorsal raphe nucleus (DRN) of males independent of genotype, but there were no changes in the median raphe nucleus (MRN) or in SERT binding density. METH treatment reduced the number of TPH2 positive cells in ventral subregions of the rostral and medial DRN independent of genotype. METH treatment selectively reduced DRN cell counts in BDNF HET mice compared to wildtype mice in medial and caudal ventrolateral subregions previously associated with panic-like behaviour. The data increase our understanding of the long-term and selective effects of METH on brain serotonin systems. These findings could be relevant for some of the psychosis-like symptoms associated with long-term METH use.