Bile Acids as Signaling Molecules: Role of Ursodeoxycholic Acid in Cholestatic Liver Disease.

Ursodeoxycholic acid (UDCA) is a natural substance physiologically produced in the liver. Initially used to dissolve gallstones, it is now successfully used in treating primary biliary cirrhosis and as adjuvant therapy for various hepatobiliary cholestatic diseases. However, the mechanisms underlying its beneficial effects still need to be clarified. Evidence suggests three mechanisms of action for UDCA that could benefit humans with cholestatic liver disease (CLD): protection of cholangiocytes against hydrophobic bile acid (BA) cytotoxicity, stimulation of hepatobiliary excretion, and protection of hepatocytes against BA-induced apoptosis. These mechanisms may act individually or together to potentiate them. At the molecular level, it has been observed that UDCA can generate modifications in the transcription and translation of proteins essential in the transport of BA, correcting the deficit in BA secretion in CLD, in addition to activating signaling pathways to translocate these transporters to the sites where they should fulfill their function. Inhibition of BA-induced hepatocyte apoptosis may play a role in CLD, characterized by BA retention in the hepatocyte. Thus, different mechanisms of action contribute to the improvement after UDCA administration in CLD. On the other hand, the effects of UDCA on tissues that possess receptors that may interact with BAs in pathological contexts, such as skeletal muscle, are still unclear. This work aims to describe the main molecular mechanisms by which UDCA acts in the human body, emphasizing the interaction in tissues other than the liver.

[Hospitalary concurrent exercise program in overweight and obese school students and adolescents during COVID-19 pandemic]. / Programa de ejercicio concurrente hospitalario en escolares y adolescentes con sobrepeso y obesidad durante la pandemia COVID-19.

The COVID-19 pandemic reduced daily physical activity in the pediatric population, with deleterious effects on anthropometry, muscle function, aerobic capacity, and metabolic control. OBJECTIVE: Determine the changes in anthropometry, aerobic capacity, muscle function, and metabolic control of a 12-week concurrent training protocol in overweight and obese children and adolescents during the COVID-19 pandemic. PATIENTS AND METHOD: 24 patients participated and were divided into groups once a week (12S; n = 10) and twice a week (24S; n = 14). Anthropometry, muscle function, aerobic capacity, and metabolic biochemical tests were evaluated before and after the application of the concurrent training plan. Two-way ANOVA, Kruskal-Wallis test, and Fisher's post hoc test were used. RESULTS: Only the twice times week training improved the anthropometrics parameters (BMI - z, waist circumference and waist to height ratio). The muscle function tests (push up, standing broad jump and prone plank), improved in both groups such as the aerobic capacity measured by VO2maximo and the runned distance in Shuttle 20m run test. The HOMA index only improved with twice times week training without changes in lipid profile in both groups. CONCLUSIONS: The 12S and 24S groups improved aerobic capacity and muscular function. Only the 24S improved anthropometric parameters and the HOMA index.

Impact of a Community-Based Pelvic Floor Kinesic Rehabilitation Program on the Quality of Life of Chilean Adult Women with Urinary Incontinence.

The pelvic floor forms the primary bottom tissue of the pelvic cavity. It comprises muscles that play a fundamental role in bowel and bladder emptying. Alterations of pelvic floor muscles will result in dysfunctions such as urinary incontinence (UI). Given the high prevalence of UI and its impact on the quality of life (QoL) in patients with pelvic floor muscle dysfunctions, it is necessary to implement public, community, and generalized programs focused on treating these dysfunctions. OBJECTIVE: To determine the effect of a community rehabilitation program on QoL, UI severity, and pelvic floor muscle strength in patients with UI. PATIENTS AND METHOD: A descriptive prospective cohort study. Twenty subjects between 44 and 75 years old with a diagnosis of UI, participants of a community kinesic rehabilitation program on the pelvic floor in Maipú, Santiago, Chile, were evaluated. These volunteers were intervened for six months, and QoL was measured with the 36-Item Short-Form Health Survey (SF-36) and International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) scales, UI severity with the Sandvick test, and pelvic floor muscle strength with the Oxford scale. Patients were followed up three months post-intervention. RESULTS: Significant improvements were observed in all scales after applying for the community kinesic rehabilitation program, and the changes were maintained at a 3-month follow-up. CONCLUSIONS: Since the improvement in QoL, UI severity, and pelvic floor muscle strength after the intervention, it is relevant to consider the implementation of community programs aimed at education, screening, and early rehabilitation of these patients.

Differential Fibrotic Response of Muscle Fibroblasts, Myoblasts, and Myotubes to Cholic and Deoxycholic Acids.

Fibrosis is a condition characterized by an increase in the components of the extracellular matrix (ECM). In skeletal muscle, the cells that participate in the synthesis of ECM are fibroblasts, myoblasts, and myotubes. These cells respond to soluble factors that increase ECM. Fibrosis is a phenomenon that develops in conditions of chronic inflammation, extensive lesions, or chronic diseases. A pathological condition with muscle weakness and increased bile acids (BA) in the blood is cholestatic chronic liver diseases (CCLD). Skeletal muscle expresses the membrane receptor for BA called TGR5. To date, muscle fibrosis in CCLD has not been evaluated. This study aims to assess whether BA can induce a fibrotic condition in muscle fibroblasts, myoblasts, and myotubes. The cells were incubated with deoxycholic (DCA) and cholic (CA) acids, and fibronectin protein levels were evaluated by Western blot. In muscle fibroblasts, both DCA and CA induced an increase in fibronectin protein levels. The same response was found in fibroblasts when activating TGR5 with the specific receptor agonist (INT-777). Interestingly, DCA reduced fibronectin protein levels in both myoblasts and myotubes, while CA did not show changes in fibronectin protein levels in myoblasts and myotubes. These results suggest that DCA and CA can induce a fibrotic phenotype in muscle-derived fibroblasts. On the other hand, DCA decreased the fibronectin in myoblasts and myotubes, whereas CA did not show any effect in these cell populations. Our results show that BA has different effects depending on the cell population to be analyzed.

[Evaluation and follow-up in functionality in patients with Pediatric Multisystem Inflammatory Syndrome associated with COVID-19 (MIS-C)]. / Evaluación y seguimiento de funcionalidad en pacientes con Síndrome Inflamatorio Multisistémico Pediátrico asociado a COVID-19 (SIM-C).

In June 2020 appeared the first cases of Multisystem Inflammatory Syndrome in Children (MIS C) associated with COVID-19 in Chile. Possible sequelae associated with this condition are still unknown. OBJECTIVE: To describe the functional status of children with MIS-C admitted to a high complexity Hospital. PATIENTS AND METHOD: Descriptive, prospective study. Sample of 28 patients. The functional status was evaluated during Hospitalization, and in the first and fourth months after discharge with the Functional Status Scale (FSS), Pediatric Evaluation of Disability Inventory (PEDI- CAT), 6-minute walk test (6MWT), PImax and PEmax, and dynamometry. Post-Traumatic Stress Disorder was screened with the Child PTSD Symptom Scale (CPSS). RESULTS: Mean age 63.6 months. Sixteen were women and 60.7% presented no comorbidities. Half of the cases presented with Shock. Mean hospitalization was 9 days. Twenty-two patients were admitted to the ICU; 54% required me chanical ventilation and/or vasoactive drugs, and 82% had cardiac repercussions. During hospitaliza tion, 82.3% presented some physical alteration, 29.1% of them were confirmed ICU-acquired weak ness (ICU-AW), and 16.6% were suspected cases. Thirteen patients presented emotional symptoms, 39.2% had post-ICU syndrome. Most of the patients (58.8%) had an unfavorable Functional Situa tion and recovered 4 months post-discharge. All patients reversed echocardiographic abnormalities in the first month and regained muscle strength in the fourth month. 38.5% of subjects reported su boptimal values in the 6MWT and 66.6% presented alteration in the post-traumatic stress screening. CONCLUSION: Most of the patients presented functional compromise with favorable recovery despite the severity of the symptoms and possible secondary complications after ICU.

[Effect of a 12-week concurrent planification exercise program in overweight and obese children and adolescents]. / Efectos de una planificación de ejercicio concurrente de 12 semanas en niños, niñas y adolescentes con sobrepeso y obesidad.

OBJECTIVE: To determine the changes in a planned concurrent exercise protocol in overweight and obese children and adolescents who attend a cardiometabolic rehabilitation program at the Dr. Exequiel González Cortés hospital. PATIENTS AND METHOD: 32 patients were divided into two groups, the intervention group (INT) (n = 22; age: 12.9 ± 2.7), and the control group (CON) (n = 10; age: 12.6 ± 2.5). The INT performed 12 weeks of periodized concurrent training protocol, those who voluntarily left the program made up the CON. The measurements were made on three consecutive days; day 1: pre-participation cardiovascular evaluation and anthropometry, day 2: aerobic capacity and muscle function, and day 3: lipid profile and glycemic control. RESULTS: The INT presented a decrease in the body mass index (BMI) (-0.77 ± 1.02 kilogram/meter2; P=0.001), BMI z-score (-0.14 ± 0.20 Standard Deviation; P=0.002), waist circumference (-5.48 ± 6.42 centimeters; P = 0.0004), and waist to height ratio (-0.04 ± 0.04; P < 0.0001). Maximal oxygen consumption (2.24 ± 2.15 milliliters/kilogram/ minutes; P < 0.0001) and walked distance (104.55 ± 119.35 meters; P < 0.0001) improved in the INT. The push-ups 6.00 repetitions interquartile range (IQR) (4.00 - 11.00; P = 0.0001), standing broad jump 16.00 centimeters IQR (8.00 - 21.25; P = 0.004), and prone plank 56,00 seconds IQR (38.00 - 73.00; P < 0.0001), improved in the INT, in addition to presenting a decrease in total cholesterol -11.00 milligram/deciliters IQR (-18.50 - 3.50; P = 0.02). Glycemic control did not change between both groups. CONCLUSIONS: A 12-week planned concurrent exercise protocol of twelve weeks is effective to improve anthropometry, aerobic capacity, muscle function, and total cholesterol in overweight and obese children and adolescents.