The preventive and therapeutic consumption of meat enriched with carob fruit extract, rich in phenolic compounds, improves colonic antioxidant status in late-stage T2DM rats.

Oxidative stress is prevalent in Type 2 Diabetes Mellitus (T2DM) and has been associated with high meat consumption. Carob Fruit Extract (CFE) contains phenolic compounds, making it a suitable functional ingredient. Current study aims to evaluate the effect of CFE-enriched meat (CFE-meat) consumption on the antioxidant status of proximal and distal colon, and its relationship with fecal phenolic compounds in late-stage T2DM rats. Three groups of eight rats were studied: 1) D, fed control-meat; 2) ED, fed CFE-meat since the beginning of the study; 3) DE, fed CFE-meat after confirming T2DM. CFE-meat consumption reduces colonic oxidative stress mainly in the proximal section and helps to ameliorate glutathione metabolism and antioxidant score. Difference between ED and DE groups were associated with colon homeostasis and T2DM progression suggesting greater fermentation but lower absorption in the DE group. CFE appears as a promising tool to improve the antioxidant status observed in late-stage T2DM.

Analysis of immunohistomorphological changes in the colonic mucosa in a high-saturated fat and high-cholesterol fed streptozotocin/nicotinamide diabetic rat model.

The mucosal surface of gastrointestinal tract is lined with epithelial cells that establish an effective barrier between the lumen and internal environment through intercellular junctions, preventing the passage of potentially harmful substances. The "intestinal barrier function" consist of a defensive system that prevent the passage of antigens, toxins, and microbial products, while maintains the correct development of the epithelial barrier, the immune system and the acquisition of tolerance toward dietary antigens and intestinal microbiota. Intestinal morphology changes subsequent to nutritional variations, stress, aging or diseases, which can also affect the composition of the microbiota, altering the homeostasis of the intestine. A growing body of evidence suggests that alterations in intestinal barrier function favor the development of exaggerated immune responses, leading to metabolic endotoxemia, which seems to be the origin of many chronic metabolic diseases such as type 2 diabetes mellitus (T2DM). Although the mechanisms are still unknown, the interaction between dietary patterns, gut microbiota, intestinal mucosa, and metabolic inflammation seems to be a key factor for the development of T2DM, among other diseases. This chapter details the different techniques that allow evaluating the morphological and molecular alterations that lead of the intestinal barrier dysfunction in a T2DM experimental model. To induce both diabetic metabolic disturbances and gut barrier disruption, Wistar rats were fed a high-saturated fat and high-cholesterol diet and received a single dose of streptozotocin/nicotinamide. This animal model may contribute to clarify the understanding of the role of intestinal barrier dysfunction on the late-stage T2DM etiology.

Periodontitis and rheumatoid arthritis-Global efforts to untangle two complex diseases.

Understanding the impact of oral health on rheumatoid arthritis (RA) will inform how best to manage patients with both periodontitis and RA. This review seeks to provide an update on interventional and mechanistic investigations, including a brief summary of European Research programs investigating the link between periodontitis and RA. Recent clinical studies are described that evaluate how the treatment of one disease impacts on the other, as are studies in both humans and animal models that have sought to identify the potential mechanisms linking the two diseases.

Silicon-enriched meat positively improves plasma lipidaemia and lipoproteinaemia, LDLr, and insulin capability and the signalling pathway induced by an atherogenic diet in late-stage type 2 diabetes mellitus rats.

The impact of silicon as a functional ingredient in restructured meat (RM) on lipoprotein composition, metabolism, and oxidation on type 2 diabetes mellitus (T2DM) markers has never been studied. This study aims to evaluate the effect of silicon-enriched-meat consumption on lipidaemia, lipoprotein profile and metabolism, plasma arylesterase, and TBARS and their relationships with glycaemia, insulinaemia, and insulin-signaling markers in late-stage-T2DM rats fed a high-saturated-fat-high-cholesterol (HSFHC) diet. Saturated-fat diets with or without added cholesterol were formulated by mixing a 70% purified diet with 30% freeze-dried RM with or without added silicon. Three groups of seven Wistar rats each were tested. The ED group received the control RM in the framework of a high-saturated-fat diet as early-stage T2DM control. The other two groups received streptozotocin-nicotinamide administration together with the HSFHC diet containing the control RM (LD) or silicon-enriched RM (LD-Si). Scores were created to define the diabetic trend and dyslipidaemia. The ED rats showed hyperglycaemia, hyperinsulinaemia, hypertriglyceridaemia, and triglyceride-rich-VLDLs, suggesting they were in early-stage T2DM. LD rats presented hyperglycaemia, hypoinsulinaemia, and reduced HOMA-beta and insulin signaling markers typical of late-stage T2DM along with hypercholesterolaemia and high amounts of beta-VLDL, IDL, and LDL particles and low arylesterase activity. All these markers were significantly (p < 0.05) improved in LD-Si rats. The diabetic trend and diabetes dyslipidaemia scores showed a high and significant correlation (r = 0.595, p < 0.01). Silicon-enriched-meat consumption counterbalances the negative effects of HSFHC diets, functioning as an active hypolipemic, antioxidant, and antidiabetic dietary ingredient in a T2DM rat model, delaying the onset of late-stage diabetes.

Tubulo-interstitial inflammation increases the risk of graft loss after the recurrence of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. Methods: We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). Results: A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119-4.910, P = .024) independently of other histologic and clinical variables. Conclusions: In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies.

Abundancia de Akkermansia muciniphila según el IMC en pacientes con trastornos gastrointestinales: estudio piloto de cohorte transversal / Akkermansia muciniphila abundance according to BMI in patients with GI disorders: cross-sectional cohort pilot study

En los últimos años, Akkermansia muciniphila ha ganado prominencia en la investigación científica debido a su posible contribución a la regulación de la respuesta inmunológica, la sensibilidad a la insulina, la prevención de enfermedades inflamatorias y la salud metabólica. En concreto, su abundancia se ha correlacionado inversamente con el peso corporal y su presencia podría tener un efecto beneficioso en la regulación del metabolismo. El objetivo del presente estudio fue examinar si A. muciniphila estaba asociada con el IMC en personas con trastornos gastrointestinales. Los resultados sugieren que la abundancia de A. muciniphila es muy baja en pacientes con trastornos gastrointestinales (1,35%) y menor en personas con sobrepeso u obesidad, aunque los resultados no fueron significativos. Este estudio no pudo confirmar de forma estadísticamente significativa la hipótesis de la relación entre Akkermansia y el sobrepeso o la obesidad. Lo cual puede sugerir o una potencia del efecto menor del mismo al esperado, o la no relación directa o causal.(AU)

In recent years, Akkermansia muciniphila has gained prominence in scientific research due to its potential contribution to the regulation of immune response, insulin sensitivity, prevention of inflammatory diseases, and metabolic health. Specifically, its abundance has been inversely correlated with body weight, and its presence may have a beneficial effect on metabolism regulation. The aim of this study was to examine whether A. muciniphila was associated with BMI in individuals with gastrointestinal disorders. The results suggest that the abundance of A. muciniphila is very low in patients with gastrointestinal disorders (1.35%) and lower in individuals with overweight or obesity, although the results were not significant. This study could not confirm in a statistically significant way the hypothesis of the relationship between Akkermansia and overweight or obesity. Which may suggest either a lower power of the effect than expected, or no direct or causal relationship.(AU)

Update of the recommendations on the management of the SARS-CoV-2 coronavirus pandemic (COVID-19) in kidney transplant patients.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country. This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

Effectiveness and safety of a cement-on-cement removal system for hip and knee arthroplasty revision surgery.

Cement removal during hip or knee arthroplasty revision is challenging and not exempt of complications. Cement-on-cement procedure is among techniques developed to safe removal of cement from bone, and it could be a realistic solution. This cement-on-cement devices can provide advantages in removing bone cement during hip and knee arthroplasty septic and non-septic revision surgeries, and can be regarded as an effective and safe alternative. We present our experience using the cement-on-cement technique in 34 cases between 2010 and 2021, including revision surgeries for 20 knee and 14 hip arthroplasties. In 3 out of 34 cases the technique failed, with a success of 91%. Mean surgical time was 2.77 (SD 0.93) hours and blood transfusion was required in 23 cases. Success was achieved in every aseptic case. Of all patients, 60% were septic cases. Infection was considered to be eradicated in 70% (14/20) of patients with a septic revision. Cement-on-cement is a safe and effective alternative for cement removal during hip and knee arthroplasty revision. Level of evidence: III, retrospective case series.

Exogenous Supplementation with DAO Enzyme in Women with Fibromyalgia: A Double-Blind Placebo-Controlled Clinical Trial.

Fibromyalgia (FM) is characterized by chronic musculoskeletal pain, muscle tension, joint mobility loss, and several psychological symptoms severely affecting patient well-being. Histamine is naturally degraded in the small intestine by diamine oxidase (DAO). Hereditary or acquired DAO deficiency causes extracellular histamine accumulation, leading to symptoms similar to those of individuals diagnosed with FM. Thus, this study aimed to assess the efficacy of adding DAO supplementation for 8 weeks to their standard therapy. We randomly assigned 100 women with FM (age: 33-61 years) to the supplementation and control groups. The Fibromyalgia Impact Questionnaire (FIQ), the Pain Catastrophizing Scale (PCS), and intensity scales were applied for a series of clinical symptoms together with the Bristol scale to assess the added value of DAO supplementation. Patients in both groups were receiving complete pharmacological support but some differences in the number of subjects receiving analgesics, antidepressants, and anxiolytics was noted. Patients in both study groups experienced favorable changes during the evaluation period as indicated by their final FIQ and PCS scores, particularly in the DAO group in the latter questionnaire. Qualitatively, the patients assigned to the DAO treatment group had lower scores for fatigue, anxiety, depression, burning and for rumination, magnification, and helplessness.

Actualización de las recomendaciones en el manejo de la pandemia por coronavirus SARS-CoV-2 (COVID-19) en pacientes con trasplante renal / Update of the recommendations on the management of the SARS-CoV-2 coronavirus pandemic (COVID-19) in kidney transplant patients

La infección por el SARS-CoV-2 (COVID-19) ha supuesto un importante impacto en la actividad trasplantadora en nuestro país. Era esperable que la mortalidad y el riesgo de complicaciones asociadas a la COVID-19 en el receptor de trasplante renal (TR) fueran mayores debido a su condición de inmunosupresión y a las frecuentes comorbilidades asociadas. Desde el inicio de la pandemia en marzo del 2020 hemos mejorado rápidamente nuestro conocimiento acerca de la epidemiología, características clínicas y manejo de la COVID-19 postrasplante, redundando en un mejor pronóstico para nuestros pacientes. Las unidades de TR han sabido adaptar sus programas a esta nueva realidad, normalizándose la actividad tanto de donación como de trasplante en nuestro país. Este manuscrito presenta una propuesta de actualización de las recomendaciones generales para la prevención y el tratamiento de la infección en esta población tan vulnerable como son los receptores de un trasplante renal. (AU)

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant (KT) recipients were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country. This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT. (AU)

Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology COVID registry.

INTRODUCTION: SARS CoV2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient`s clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. OBJECTIVES: Evaluate the management of immunosuppressive therapy made during SARS-CoV2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID19 diagnosis. MATERIAL AND METHODS: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. RESULTS: renal transplant recipients with COVID19 were included (62.6% male), with a mean age of 57.5 years. The predominant immunosuppressive treatment prior to COVID19 was triple therapy with prednisone, tacrolimus and mycophenolic acid (54.6%) followed by m-TOR inhibitor regimens (18.6%). After diagnosis of infection, mycophenolic acid was discontinued in 73.8% of patients, m-TOR inhibitor in 41.4%, tacrolimus in 10.5% and cyclosporin A in 10%. In turn, 26.9% received dexamethasone and 50.9% were started on or had their baseline prednisone dose increased. Mean creatinine before diagnosis of COVID19, at diagnosis and at 6 months was: 1.7 ±â€¯0.8, 2.1 ±â€¯1.2 and 1.8 ±â€¯1 mg/dl respectively (p < 0.001). 56.9% of the patients (N = 350) were monitored for anti-HLA antibodies. 94% (N = 329) had no anti-HLA changes, while 6% (N = 21) had positive anti-HLA antibodies. Among the patients with donor-specific antibodies post-COVID19 (N = 9), 7 patients (3.1%) had one immunosuppressant discontinued (5 patients had mycophenolic acid and 2 had tacrolimus), 1 patient had both immunosuppressants discontinued (3.4%) and 1 patient had no change in immunosuppression (1.1%), these differences were not significant. CONCLUSIONS: The management of immunosuppressive therapy after diagnosis of COVID19 was primarily based on discontinuation of mycophenolic acid with very discrete reductions or discontinuations of calcineurin inhibitors. This immunosuppression management did not influence renal function or changes in anti-HLA antibodies 6 months after diagnosis.

Impact of Silicon Addition on the Development of Gelled Pork Lard Emulsions with Controlled Lipid Digestibility for Application as Fat Replacers.

Pork lard gelled emulsions stabilized with two proteins [soy protein concentrate (SPC) or a pork rind protein extract (PRP)], both with and without added silicon (Si) from diatomaceous earth powder, were gelled by microbial transglutaminase and к-carrageenan. These gelled emulsions (GEs), intended as fat replacers, were evaluated in different aspects, including microstructure and technological properties during chilling storage. In addition, in vitro gastrointestinal digestion (GID) with an analysis of lipolysis and lipid digestibility was also evaluated. All GEs showed adequate technological properties after 28 days of chilling storage, although the SPC-stabilized GEs showed better gravitational and thermal stability (~4% and ~6%, respectively) during chilling storage than the PRP-stabilized ones (~8 and ~12%, respectively). PRP developed larger flocculates restricting pancreatic lipase-mediated lipolysis during intestinal digestion. The addition of Si to both GE structures protected them against disruption during in vitro digestion. Accordingly, Si appears to slow down fat digestion, as reflected by higher triacylglycerides content after GID (15 and 22% vs. 10 and 18% in GEs without Si) and could become a potential candidate for use in the development of healthier meat products.

Dietary Supplementation with a Cocoa-Carob Blend Modulates Gut Microbiota and Prevents Intestinal Oxidative Stress and Barrier Dysfunction in Zucker Diabetic Rats.

We have recently developed a cocoa-carob blend (CCB) rich in polyphenols with antidiabetic properties. In this study, we investigated whether its benefits could be related to gut health and gut microbiota (GM) composition and the likely phenolic metabolites involved. Zucker diabetic fatty rats were fed on a standard or a CCB-rich diet for 12 weeks. Intestinal barrier structure and oxidative and inflammatory biomarkers were analyzed in colonic samples. GM composition and phenolic metabolites were evaluated from feces. The results show that CCB improved mucin and tight-junction proteins and counteracted gut oxidative stress and inflammation by regulating sirtuin-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) levels. CCB also modulated the composition of the GM, showing increases in Akkermansia and Bacteroides and decreases in Ruminococcus genera. Correlation analysis strengthened the associations between these genera and improved pathological variables in diabetic animals. Moreover, 12 phenolic metabolites were identified in CCB feces, being2,3-dihydroxybenzoic and 3,4,5-trihydroxybenzoic acids significantly associated with increased levels of Akkermansia and Oscillospira genera. Our findings support the potential use of CCB to prevent intestinal damage and dysbiosis in T2D, which would help to delay the progression of this pathology.

The bitter taste receptor (TAS2R) agonist denatonium promotes a strong relaxation of rat corpus cavernosum.

Bitter taste receptors (TAS2R) are found in numerous extra-oral tissues, including smooth muscle (SM) cells in both vascular and visceral tissues. Upon activation, TAS2R stimulate the relaxation of the SM. Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling pathway is involved in penile erection, and type 5 phosphodiesterase (PDE5) inhibitors, a cGMP-specific hydrolase are used as first-line treatments for erectile dysfunction (ED). Nevertheless, PDE5 inhibitors are ineffective in a considerable number of patients, prompting research into alternative pharmacological targets for ED. Since TAS2R agonists regulate SM contractility, this study investigates the role of TAS2Rs in rat corpus cavernosum (CC). We performed immunohistochemistry to detect TAS2R10, isometric force recordings for TAS2R agonists denatonium and chloroquine, the slow-release H2S donor GYY 4137, the NO donor SNAP, the ß-adrenoceptor agonist isoproterenol and electrical field stimulation (EFS), as well as measurement of endogenous hydrogen sulfide (H2S) production. The immunofluorescence staining indicated that TAS2R10 was broadly expressed in the CC SM and to some extent in the nerve fibers. Denatonium, chloroquine, SNAP, and isoproterenol cause potent dose-dependent SM relaxations. H2S production was decreased by NO and H2S synthase inhibitors, while it was enhanced by denatonium. In addition, denatonium increased the relaxations induced by GYY 4137 and SNAP but failed to modify EFS- and isoproterenol-induced responses. These results suggest neuronal and SM TAS2R10 expression in the rat CC, where denatonium induces a strong SM relaxation per se and promotes the H2S- and NO-mediated inhibitory gaseous neurotransmission. Thus, TAS2R10 might represent a valuable therapeutic target in ED.

Manejo de la inmunosupresión en pacientes trasplantados de riñón con COVID19. Estudio multicéntrico nacional derivado del registro COVID de la Sociedad Española de Nefrología / Management of immunosuppressive therapy in kidney transplant recipients with COVID-19. A multicentre national study derived from the Spanish Society of Nephrology. COVID registry

Introducción: La infección por SARS-CoV2 ha impactado de forma importante en los pacientes con trasplante renal causando una elevada mortalidad en los primeros meses de la pandemia. La reducción intencionada de la inmunosupresión se ha postulado como uno de los pilares en el manejo de la infección ante la falta de un tratamiento antiviral dirigido. Esta se ha modificado de acuerdo con la situación clínica de los pacientes, y su efecto sobre la función renal o los anticuerpos anti-HLA a medio plazo no ha sido evaluado. Objetivos: Evaluar los cambios de inmunosupresión realizados durante la infección por SARS-CoV2, así como la función renal y los anticuerpos anti-HLA de los pacientes trasplantados de riñón a los 6 meses del diagnóstico de COVID19. Material y métodos: Estudio retrospectivo, multicéntrico nacional (30 centros) de pacientes trasplantados de riñón con COVID19 desde el 01/02/20 al 31/12/20. Se recogieron las variables de la historia clínica y se incluyeron en una base de datos anonimizada. Se utilizó el programa estadístico SPSS para el análisis de resultados. (AU)

Introduction: SARS-CoV-2 infection has had a major impact on renal transplant patients with a high mortality in the first months of the pandemic. Intentional reduction of immunosuppressive therapy has been postulated as one of the cornerstone in the management of the infection in the absence of targeted antiviral treatment. This has been modified according to the patient's clinical situation and its effect on renal function or anti-HLA antibodies in the medium term has not been evaluated. Objectives: Evaluate the management of immunosuppressive therapy made during SARS-CoV-2 infection, as well as renal function and anti-HLA antibodies in kidney transplant patients 6 months after COVID-19 diagnosis. Material and methods: Retrospective, national multicentre, retrospective study (30 centres) of kidney transplant recipients with COVID19 from 01/02/20 to 31/12/20. Clinical variables were collected from medical records and included in an anonymised database. SPSS statistical software was used for data analysis. (AU)

Effect of MetioNac® in patients with metabolic syndrome who are at risk of metabolic dysfunction associated fatty liver disease: a randomized controlled trial / Efecto de MetioNac® en pacientes con síndrome metabólico que están en riesgo de padecer enfermedad de hígado graso asociado a disfunción metabólica: un estudio controlado aleatorizado

Introduction: metabolic syndrome comprises a combination of diabetes, high blood pressure, and obesity, and metabolic associated fatty liver disease (MAFLD) is associated with it. Objective: to evaluate the effect of supplementation with S-adenosyl-L-methionine + N-acetylcysteine + thioctic acid + vitamin B6 (MetioNac®) for 3 months on lipidic and biochemical parameters in subjects with metabolic syndrome and at risk of MAFLD. The reduction in body weight and the oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) were also evaluated. Methods: patients with metabolic syndrome, at risk of MAFLD (FIB-4 < 1.30), and with an indication for weight reduction were recruited (n = 15). Control group followed a semipersonalized Mediterranean diet (MD) for weight reduction, according to the recommendations of the Spanish Society for the Study of Obesity (SEEDO). Experimental group, in addition to the MD, took three capsules of MetioNac® supplement per day. Results: compared with the control group, subjects taking MetioNac® showed significant (p < 0.05) reductions in the levels of TG and VLDL-c, as well as in total cholesterol, LDL-c, and glucose levels. They also showed increased levels of HDL-c. Levels of AST and ALT decreased after the intervention with MetioNac®, but this decrease did not reach statistical significance. Weight loss was observed in both groups. Conclusion: supplementation with MetioNac® may be protective against hyperlipidemia, insulin resistance, and overweight among metabolic syndrome patients. Further studies on this issue are needed in a larger population.(AU)

Introducción: el síndrome metabólico se define como una combinación de diabetes, hipertensión arterial y obesidad, que se asocia con laenfermedad del hígado graso asociada a disfunción metabólica.Objetivo: evaluar el efecto de la suplementación con S-adenosil-L-metionina + N-acetilcisteína + ácido tióctico + vitamina B6 (MetioNac®)durante 3 meses sobre parámetros lipídicos y bioquímicos en sujetos con síndrome metabólico y en riesgo de enfermedad del hígado grasoasociada a disfunción metabólica. También se evaluaron la reducción del peso corporal y los marcadores de estrés oxidativo malondialdehído(MDA) y superóxido dismutasa (SOD).Métodos: se reclutaron pacientes con síndrome metabólico, riesgo de enfermedad del hígado graso asociada a disfunción metabólica (FIB-4 < 1,30) y con indicación de reducción de peso (n = 15). El grupo control siguió una dieta mediterránea (DM) semipersonalizada para la reducciónde peso, de acuerdo con las recomendaciones de la Sociedad Española para el Estudio de la Obesidad (SEEDO). El grupo intervención, ademásde la DM, tomó tres cápsulas diarias de MetioNac®.Resultados: en comparación con el grupo de control, los sujetos que tomaron MetioNac® mostraron reducciones significativas (p < 0.05) en losniveles de TG y VLDL-c, así como en los niveles de colesterol total, LDL-c y glucosa. También mostraron niveles elevados de HDL-c. Los nivelesde AST y ALT disminuyeron después de la intervención con MetioNac®, pero esta disminución no fue estadísticamente significativa. También seobservó una pérdida de peso en ambos grupos.Conclusión: la suplementación con MetioNac® puede proteger contra la hiperlipidemia, la insulinorresistencia y el sobrepeso en pacientes consíndrome metabólico. Sin embargo, es necesario realizar más estudios y seleccionar un mayor número de participantes.(AU)

Effect of MetioNac® in patients with metabolic syndrome who are at risk of metabolic dysfunction associated fatty liver disease: a randomized controlled trial.

Introduction: Introduction: metabolic syndrome comprises a combination of diabetes, high blood pressure, and obesity, and metabolic associated fatty liver disease (MAFLD) is associated with it. Objective: to evaluate the effect of supplementation with S-adenosyl-L-methionine + N-acetylcysteine + thioctic acid + vitamin B6 (MetioNac®) for 3 months on lipidic and biochemical parameters in subjects with metabolic syndrome and at risk of MAFLD. The reduction in body weight and the oxidative stress markers malondialdehyde (MDA) and superoxide dismutase (SOD) were also evaluated. Methods: patients with metabolic syndrome, at risk of MAFLD (FIB-4 < 1.30), and with an indication for weight reduction were recruited (n = 15). Control group followed a semipersonalized Mediterranean diet (MD) for weight reduction, according to the recommendations of the Spanish Society for the Study of Obesity (SEEDO). Experimental group, in addition to the MD, took three capsules of MetioNac® supplement per day. Results: compared with the control group, subjects taking MetioNac® showed significant (p < 0.05) reductions in the levels of TG and VLDL-c, as well as in total cholesterol, LDL-c, and glucose levels. They also showed increased levels of HDL-c. Levels of AST and ALT decreased after the intervention with MetioNac®, but this decrease did not reach statistical significance. Weight loss was observed in both groups. Conclusion: supplementation with MetioNac® may be protective against hyperlipidemia, insulin resistance, and overweight among metabolic syndrome patients. Further studies on this issue are needed in a larger population.

Introducción: Introducción: el síndrome metabólico se define como una combinación de diabetes, hipertensión arterial y obesidad, que se asocia con la enfermedad del hígado graso asociada a disfunción metabólica. Objetivo: evaluar el efecto de la suplementación con S-adenosil-L-metionina + N-acetilcisteína + ácido tióctico + vitamina B6 (MetioNac®) durante 3 meses sobre parámetros lipídicos y bioquímicos en sujetos con síndrome metabólico y en riesgo de enfermedad del hígado graso asociada a disfunción metabólica. También se evaluaron la reducción del peso corporal y los marcadores de estrés oxidativo malondialdehído (MDA) y superóxido dismutasa (SOD). Métodos: se reclutaron pacientes con síndrome metabólico, riesgo de enfermedad del hígado graso asociada a disfunción metabólica (FIB-4 < 1,30) y con indicación de reducción de peso (n = 15). El grupo control siguió una dieta mediterránea (DM) semipersonalizada para la reducción de peso, de acuerdo con las recomendaciones de la Sociedad Española para el Estudio de la Obesidad (SEEDO). El grupo intervención, además de la DM, tomó tres cápsulas diarias de MetioNac®. Resultados: en comparación con el grupo de control, los sujetos que tomaron MetioNac® mostraron reducciones significativas (p < 0.05) en los niveles de TG y VLDL-c, así como en los niveles de colesterol total, LDL-c y glucosa. También mostraron niveles elevados de HDL-c. Los niveles de AST y ALT disminuyeron después de la intervención con MetioNac®, pero esta disminución no fue estadísticamente significativa. También se observó una pérdida de peso en ambos grupos. Conclusión: la suplementación con MetioNac® puede proteger contra la hiperlipidemia, la insulinorresistencia y el sobrepeso en pacientes con síndrome metabólico. Sin embargo, es necesario realizar más estudios y seleccionar un mayor número de participantes.

Cumulative effect of AOC1 gene variants on symptoms and pathological conditions in adult women with fibromyalgia: a pilot study.

Introduction: The amine oxidase copper-containing 1 (AOC1) gene encodes for the diamine oxidase (DAO) enzyme. DAO is an enzyme that catabolizes some molecules, including histamine, and is the degradative enzyme in the polyamine catabolic pathway that is active in intestinal mucosal cells. Variants of AOC1 are associated with reduced DAO activity, resulting in accumulation of high levels of histamine and causing a wide range of neurological, gastrointestinal, and epidermal disorders, which are present in people with fibromyalgia. This study aimed to evaluate the impact of four AOC1 gene variants, namely, rs10156191, rs1049742, rs1049793, and rs2052129, on fibromyalgia symptoms measured by the Fibromyalgia Impact Questionnaire (FIQ), such as sleep disorders, atopic dermatitis, migraine, gastrointestinal (GI) disorders, allergies, and intolerances, in adult women with fibromyalgia. Methods: The sample consisted of 100 unrelated women with fibromyalgia between 33 and 60 years of age (48.48 years ±7.35), whose were diagnosed by a rheumatologist based on symptoms such as pain, stiffness, and fatigue. Single-nucleotide polymorphisms (SNPs) of AOC1 were identified using oral mucosa samples collected following a standard hygiene protocol. DNA was extracted, and gene variants of interest were analyzed using multiplex single-nucleotide primer extension (SNPE). Clinical data were collected using the FIQ and a series of variables that quantified the intensity and frequency of the symptoms. Results: The minor allele frequencies of rs10156191, rs1049742, rs1049793, and rs2052129 were 31.5, 10, 32.5, and 27%, respectively. Each variant was found to be in Hardy-Weinberg equilibrium, but partial linkage disequilibrium between AOC1 SNPs is suspected. The results show that fibromyalgia symptoms measured using the FIQ tend to increase with the number of risk alleles and that the intensity of dry skin and low stool consistency may be associated with an increase in the number of these alleles. Conclusion: This study constitutes the first step in investigating associations between fibromyalgia symptoms and candidate variants of the AOC1 gene in DAO enzyme activity. Identification of reduced DAO activity may improve the quality of life and treatment of symptoms in fibromyalgia patients.

Influencia del consumo crónico de estatinas en el estado de hidratación de personas mayores / Influence of chronic statin use on the hydration status of older people

Introducción: Las personas de edad avanzada en tratamiento crónico con fármacos son uno de los grupos de población con mayor riesgo de desarrollar alteraciones en el estado de hidratación. Uno de los fármacos más consumidos por este grupo de población y que pueden desencadenar la aparición de deshidratación son las estatinas. Sin embargo, hasta la fecha, estas interacciones no se han estudiado en profundidad. Objetivo: El objetivo del presente estudio fue evaluar la influencia del consumo crónico de estatinas sobre el estado de hidratación en personas de edad avanzada que acuden a la farmacia comunitaria. Métodos: Se llevó a cabo un estudio de casos y controles en voluntarios de edades comprendidas entre los 60 y 79 años residentes en Madrid, consumidores crónicos de estatinas (casos) y pacientes del mismo rango de edad, no consumidores de fármacos de forma crónica (controles). Resultados: El análisis de los datos generales de la población revelaron una elevada prevalencia de sobrepeso y obesidad, así como un elevado porcentaje de grasa corporal. Por su parte, el análisis de orina evidenció un mejor estado de hidratación de las mujeres frente a los hombres. Respecto al efecto de las estatinas en el estado de hidratación, se observó que los distintos parámetros analizados de los pacientes en tratamiento crónico con estatinas eran indicativos de deshidratación, frente al adecuado estado de hidratación de los pacientes sin tratamiento. Estos resultados se confirmaron con el análisis de la prevalencia de deshidratación en los distintos grupos. Conclusiones: Se concluye del presente estudio la importancia de monitorizar el consumo crónico de fármacos, como las estatinas, en las personas de edad avanzada, para evitar el desarrollo de patologías, incluyendo la aparición de deshidratación y sus complicaciones asociadas. Los farmacéuticos comunitarios como profesionales expertos en el medicamento son los profesionales más idóneos para llevar a cabo este seguimiento. (AU)

Introduction: Elderly people on chronic drug treatment are one of the population groups with the highest risk of developing alterations in hydration status. One of the drugs most consumed by this population group and that can trigger the onset of dehydration are statins. However, up to date, these interactions have not been studied in depth. Objective: The objective of this study was to evaluate the influence of chronic statin consumption on hydration status in elderly people attending the community pharmacy.Methods: A case-control study was conducted in volunteers aged between 60 and 79 years living in Madrid, chronic statin users (cases) and patients of the same age range, non-users of statin drugs. chronic form (controls). Results: Analysis of general population data revealed a high prevalence of overweight and obesity, as well as a high percentage of body fat. On the other hand, the urinalysis showed a better hydration status of women compared to men. Regarding the effect of statins on hydration status, it was observed that the different parameters analyzed in patients on chronic statin treatment were indicative of dehydration, compared to the adequate hydration status of patients without treatment. These results were confirmed by analyzing the prevalence of dehydration in the different groups. Conclusions: The importance of monitoring the chronic consumption of drugs, such as statins, in the elderly, to avoid the development of pathologies, including the appearance of dehydration and its associated complications, is concluded from the present study. Community pharmacists as expert professionals in the medication are the most suitable professionals to carry out this follow-up. (AU)

Proanthocyanidins: Impact on Gut Microbiota and Intestinal Action Mechanisms in the Prevention and Treatment of Metabolic Syndrome.

The metabolic syndrome (MS) is a cluster of risk factors, such as central obesity, hyperglycemia, dyslipidemia, and arterial hypertension, which increase the probability of causing premature mortality. The consumption of high-fat diets (HFD), normally referred to high-saturated fat diets, is a major driver of the rising incidence of MS. In fact, the altered interplay between HFD, microbiome, and the intestinal barrier is being considered as a possible origin of MS. Consumption of proanthocyanidins (PAs) has a beneficial effect against the metabolic disturbances in MS. However, there are no conclusive results in the literature about the efficacy of PAs in improving MS. This review allows a comprehensive validation of the diverse effects of the PAs on the intestinal dysfunction in HFD-induced MS, differentiating between preventive and therapeutic actions. Special emphasis is placed on the impact of PAs on the gut microbiota, providing a system to facilitate comparison between the studies. PAs can modulate the microbiome toward a healthy profile and strength barrier integrity. Nevertheless, to date, published clinical trials to verify preclinical findings are scarce. Finally, the preventive consumption of PAs in MS-associated dysbiosis and intestinal dysfunction induced by HFD seems more successful than the treatment strategy.