Cardio-renal benefits of sacubitril/valsartan in patients with advanced chronic kidney disease: experience in daily clinical practice.

BACKGROUND: The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4). METHODS: This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed. RESULTS: The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m2 and the left ventricular ejection fraction (LVEF) 36.4 ± 8.9%. The GFR improved after initiating the treatment (F = 3.396, p = 0.019), as did the LVEF at one year of follow-up (p = 0.018). The number of visits to the emergency department for heart failure was also reduced. No patients needed to start renal replacement therapy. CONCLUSIONS: This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.

Rerouting Cellular Electron Flux To Increase the Rate of Biological Methane Production.

Methanogens are anaerobic archaea that grow by producing methane, a gas that is both an efficient renewable fuel and a potent greenhouse gas. We observed that overexpression of the cytoplasmic heterodisulfide reductase enzyme HdrABC increased the rate of methane production from methanol by 30% without affecting the growth rate relative to the parent strain. Hdr enzymes are essential in all known methane-producing archaea. They function as the terminal oxidases in the methanogen electron transport system by reducing the coenzyme M (2-mercaptoethane sulfonate) and coenzyme B (7-mercaptoheptanoylthreonine sulfonate) heterodisulfide, CoM-S-S-CoB, to regenerate the thiol-coenzymes for reuse. In Methanosarcina acetivorans, HdrABC expression caused an increased rate of methanogenesis and a decrease in metabolic efficiency on methylotrophic substrates. When acetate was the sole carbon and energy source, neither deletion nor overexpression of HdrABC had an effect on growth or methane production rates. These results suggest that in cells grown on methylated substrates, the cell compensates for energy losses due to expression of HdrABC with an increased rate of substrate turnover and that HdrABC lacks the appropriate electron donor in acetate-grown cells.

Obesity and Cardiovascular Risk Improvement Using Cacao By-Products in a Diet-Induced Obesity Murine Model.

In the production of chocolate, only cocoa seeds are used, generating by-products that are generally discarded, increasing the risk of environmental contamination. Given fiber, carbohydrates, proteins, and flavonoid content the use of cacao pod husks can generate nutraceutical products for human consumption. In contrast, obesity represents a major public health problem worldwide. Cacao derivatives are able to modulate overweight and lipid disorders. The objective of present work was to prepare and characterize products using cacao by-products and analyze their effects on altered cardiometabolic risk markers in an obesity model induced by high fat diet and fructose ingestion in rats. The effects of a pellet and extracts made with outer pod husk and kernel husk for 5 weeks were analyzed in an obesity rat model. The treatments significantly decreased body weight by 39%, systolic blood pressure by 27%, triglycerides by 55%, total cholesterol by 24%, low-density lipoprotein cholesterol by 37%, and the triglycerides/high-density lipoprotein ratio by 54%. Cacao by-products improved the metabolic function of obese animals, without causing secondary effects.

High Flavonoid Cocoa Supplement Ameliorates Plasma Oxidative Stress and Inflammation Levels While Improving Mobility and Quality of Life in Older Subjects: A Double-Blind Randomized Clinical Trial.

BACKGROUND: The age-related decline in mass, strength, and performance of skeletal muscle is associated with loss of independence, falls risk, disability, institutionalization, and death. METHODS: To determine whether a cocoa supplement enriched in flavonoids can improve plasma markers of oxidative stress and inflammation, physical performance and frailty in middle-aged and older subjects, we conducted a two-phase, randomized, double-blind, clinical trial. The initial study included 60 subjects (55- to 70-year-old) allocated into placebo (P), highly alkalinized (no-flavonoid; NF), or flavonoid-rich natural cocoa (F) beverage groups. The follow-up study included 74 older subjects (65- to 90-year-old) randomly distributed into NF or F groups. Subjects were instructed to consume the beverages once/day for up to 12-weeks. A comprehensive (aging relevant) set of end points were assessed, which included mean change in blood plasma metabolic and oxidative stress indicators, in physical performance tests and quality of life (QoL). RESULTS: In the initial study, the F group showed improved glycemia, triglyceridemia, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, triglyceridemia/HDL index, and oxidative markers. Performance on the Up and Go test, skeletal muscle index, and quality of life also improved. In the follow-up study, F treatment was associated with significant improvements in metabolic, oxidative stress, and inflammatory endpoints and positive effects on physical performance, frailty indicators, and quality of life (F vs. NF group). CONCLUSIONS: Regular flavonoids consumption positively affects blood oxidative stress and inflammation end points, cardiometabolic risk markers, physical performance, and quality of life. The sum of such effects may help to mitigate the extent of frailty development in the elderly people. TRIAL REGISTRATION: NCT03585868.

The cardioprotective effects of (-)-Epicatechin are mediated through arginase activity inhibition in a murine model of ischemia/reperfusion.

The production of nitric oxide (NO) by nitric oxide synthases (NOS) depends on the bioavailability of L-arginine as NOS competes with arginase for this common substrate. As arginase activity increases, less NO is produced and adverse cardiovascular consequences can emerge. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao, has been reported to stimulate endothelial and neuronal NOS expression and function leading to enhanced vascular function and cardioprotective effects. However, little is known about the effects of EPI on myocardial arginase activity. The aim of the present study was to determine if EPI is able to interact and modulate myocardial arginase and NOS expression and activity. For this purpose, in silico modeling, in vitro activity assays and a rat model of ischemia/reperfusion injury were used. In silico and in vitro results demonstrate that EPI can interact with arginase and significantly decrease its activity. In vivo, 10 days of EPI pretreatment reduces ischemic myocardium arginase expression while increasing NOS expression and phosphorylation levels. Altogether, these results may partially account for the cardioprotective effects of EPI.

High-throughput mutation, selection, and phenotype screening of mutant methanogenic archaea.

Bacterial and archaeal genomes can contain 30% or more hypothetical genes with no predicted function. Phylogenetically deep-branching microbes, such as methane-producing archaea (methanogens), contain up to 50% genes with unknown function. In order to formulate hypotheses about the function of hypothetical gene functions in the strict anaerobe, Methanosarcina acetivorans, we have developed high-throughput anaerobic techniques to UV mutagenize, screen, and select for mutant strains in 96-well plates. Using these approaches we have isolated 10 mutant strains that exhibit a variety of physiological changes including increased or decreased growth rate relative to the parent strain when cells use methanol and/or acetate as carbon and energy sources. This method provides an avenue for the first step in identifying new gene functions: associating a genetic mutation with a reproducible phenotype. Mutations in bona fide methanogenesis genes such as corrinoid methyltransferases and proton-translocating F420H2:methanophenazine oxidoreductase (Fpo) were also generated, opening the door to in vivo functional complementation experiments. Irradiation-based mutagenesis such as from ultraviolet (UV) light, combined with modern genome sequencing, is a useful procedure to discern systems-level gene function in prokaryote taxa that can be axenically cultured but which may be resistant to chemical mutagens.

Co-administration of the flavanol (-)-epicatechin with doxycycline synergistically reduces infarct size in a model of ischemia reperfusion injury by inhibition of mitochondrial swelling.

(-)-Epicatechin (EPI) is cardioprotective in the setting of ischemia/reperfusion (IR) injury and doxycycline (DOX) is known to preserve cardiac structure/function after myocardial infarction (MI). The main objective of this study was to examine the effects of EPI and DOX co-administration on MI size after IR injury and to determine if cardioprotection may involve the mitigation of mitochondrial swelling. For this purpose, a rat model of IR was used. Animals were subjected to a temporary 45 min occlusion of the left anterior descending coronary artery. Treatment consisted of a single or double dose of EPI (10 mg/kg) combined with DOX (5 mg/kg). The first dose was given 15 min prior to reperfusion and the second 12 h post-MI. The effects of EPI +/- DOX on mitochondrial swelling (i.e. mPTP opening) were determined using isolated mitochondria exposed to calcium overload and data examined using isobolographic analysis. To ascertain for the specificity of EPI effects on mitochondrial swelling other flavonoids were also evaluated. Single dose treatment reduced MI size by ~46% at 48 h and 44% at three weeks. Double dosing evidenced a synergistic, 82% reduction at 3 weeks. EPI plus DOX also inhibited mitochondrial swelling in a synergic manner thus, possibly accounting for the cardioprotective effects whereas limited efficacy was observed with the other flavonoids. Given the apparent lack of toxicity in humans, the combination of EPI and DOX may have clinical potential for the treatment of myocardial IR injury.

[Candida sp endocarditis. Experience in a third-level hospital and review of the literature]. / Endocarditis por Candida sp. Experiencia en un hospital terciario y revisión de la literatura.

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report five cases of Candida endocarditis admitted to our hospital in the period between 2005 and 2011. Two cases were caused by C. albicans, two cases were caused by C. parapsilosis and in the last one, we didn't identify the species of Candida. All but one had clear risk factors for candidemia. Treatment consisted of amphotericin B with / without flucytosine in four patients, and they all underwent surgery for valve replacement and / or removal of intravascular devices. Overall mortality was 60% (40% of mortality was directly related to endocarditis). All patients who survived were given suppressive therapy with fluconazole for a minimum of two years.After stopping fluconazole there was a case of recurrence.

Beneficial effects of a flavanol-enriched cacao beverage on anthropometric and cardiometabolic risk profile in overweight subjects / Efectos beneficiosos de una bebida de cocoa enriquecida con flavanol en el perfil antropométrico y de riesgo cardiometabólico en sujetos con sobrepeso

Overweight and obesity are associated with systemic inflammation and oxidative stress which, in turn, enhance the development of cardiometabolic disruptions. Lifestyle changes and pharmacologic approaches show moderately effective results regarding overall health improvements. Evidence suggests that cacao flavonoids are associated with a reduced cardiometabolic risk, due to the modulation of molecular pathways subjacent to glucose and lipids metabolism. The aim of this study was to assess the effects of cacao flavonoids supplementation on anthropometric and cardiometabolic risk factors in overweight subjects. A double-blind, placebo-controlled, pilot clinical trial was conducted in overweight subjects with borderline criteria of metabolic syndrome. Participants were randomly assigned to either, supplement of cacao flavonoids (80 mg) or placebo, daily, for 4 weeks. Cardiometabolic variables were blood pressure, glycemia and lipid profile. Serum markers of oxidative damage (free protein carbonyls and malondialdehyde) were also analyzed. Anthropometric measurements included body weight, body mass index, waist circumference, and fat and fat-free mass. We found significant reductions in body weight (p = 0.04), waist circumference (p = 0.03), triacylglycerols (p < 0.01), TG/HDL ratio (p = 0.01), MDA (p = 0.02) and protein carbonyls (p = 0.01) in the flavonoid-supplemented group. Results from this study show that cacao flavonoids can effectively modulate anthropometric and cardiometabolic risk factors.

El sobrepeso y la obesidad están asociados con la inflamación sistémica y el estrés oxidativo, que, a su vez, incrementan el desarrollo de trastornos cardiometabólicos. Cambios en el estilo de vida y tratamientos farmacológicos muestran resultados moderadamente eficaces en relación con la mejora general de la salud. La evidencia sugiere que los flavonoides del cacao se asocian con un riesgo cardiometabólico reducido, debido a la modulación de las vías moleculares subyacentes al metabolismo de la glucosa y de los lípidos. El objetivo de este estudio fue evaluar los efectos de la suplementación de flavonoides del cacao sobre factores de riesgo cardiometabólico y antropométrico en sujetos con sobrepeso. Se llevó a cabo un ensayo clínico piloto, doble ciego y controlado con placebo en sujetos con sobrepeso y criterios limítrofes de síndrome metabólico. Los participantes fueron asignados al azar a cuatro semanas de tratamiento con suplemento oral de flavonoides de cacao (80 mg) diario o placebo. Las variables cardiometabólicas analizadas fueron presión arterial sistémica, glicemia y perfil lipídico. También se analizaron los marcadores séricos de estrés oxidativo (carbonilos proteicos libres y malondialdehído). Las medidas antropométricas incluyeron el peso corporal, índice de masa corporal, circunferencia de la cintura, masa grasa y masa libre de grasa. Se encontró una reducción significativa en el peso corporal (p = 0.04), circunferencia de la cintura (p = 0.03), triglicéridos (p < 0.01), la relación TG/HDL (p = 0.01), MDA (p = 0.02) y carbonilos (p = 0.01) en el grupo con suplemento de flavonoides. Los resultados de este estudio muestran que los flavonoides del cacao pueden modular efectivamente factores de riesgo cardiometabólico y antropométricos.

Endocarditis por Candida sp. Experiencia en un hospital terciario y revisión de la literatura / Candida sp endocarditis. Experience in a thirdlevel hospital and review of the literature

A pesar de la relativa alta frecuencia de candidemia, la endocarditis por Candida sp es una entidad rara. Describimos cinco casos de endocarditis por Candida ingresados en nuestro hospital en el período comprendido entre los años 2005-2011. Dos de los casos estaban causados por Candida albicans, dos por Candida parapsilosis, y en otro de ellos no se identificó la especie de Candida. Todos ellos, salvo uno, presentaban claros factores de riesgo de candidemia. El tratamiento consistió en anfotericina B con/sin flucitosina en cuatro de los pacientes, y en todos ellos se realizó cirugía de sustitución valvular y/o extracción de los dispositivos intravasculares. La mortalidad global fue del 60%, y en un 40% fue directamente relacionada con la endocarditis. A todos los pacientes que sobrevivieron se les administró tratamiento supresor con fluconazol durante un mínimo de dos años, tras cuya suspensión hubo un caso de recidiva(AU)

Despite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report five cases of Candida endocarditis admitted to our hospital in the period between 2005 and 2011. Two cases were caused by C. albicans, two cases were caused by C. parapsilosis and in the last one, we didn´t identify the species of Candida. All but one had clear risk factors for candidemia. Treatment consisted of amphotericin B with / without flucytosine in four patients, and they all underwent surgery for valve replacement and / or removal of intravascular devices. Overall mortality was 60% (40% of mortality was directly related to endocarditis). All patients who survived were given suppressive therapy with fluconazole for a minimum of two years.After stopping fluconazole there was a case of recurrence(AU)

Úlcera de Marjolin / Marjolin’s ulcer

En ocasiones, generalmente cuando la herida granula y cura por segunda intención así como en las secuelas por quemaduras, la cicatriz experimenta una intensa fibroplasia que empobrece la participación capilar provocando cierto grado de isquemia. El epitelio de cobertura sufre idénticas consecuencias, tornándose frágil o incompleto. Por ello, la cicatriz quedará en parte sin cubierta epitelial, o ésta desaparece de manera intermitente ante la menor agresión, desarrollándose una úlcera crónica o recidivante. Incluso, pero a más largo plazo, en ella puede terminar implantándose un carcinoma epidermoide derivado de esta situación irritativa y tórpida, hecho más común en las cicatrices postquemadura y que en ella recibe el nombre de úlcera de Marjolin, al haber sido descrita por este autor en 1828. Ante estas úlceras cicatriciales persistentes deberá procederse mediante cirugía, a extirpar por completo la zona ulcerada que debe ser sustituida mediante transplante o injerto de piel.

Sometimes when a wound granulates and it heals for second intention as well as in the sequels of burns, the scar experiments an intense fibroplasia that debilitates the capillary participation, producing some level of ischemia. The cover epithelium suffers identical consequences becoming fragile or incomplete. For this reason the scar will remain in part without this epithelium, or it disappears in a intermittent way, with the most little aggression, developing a recidivant or chronic ulcer, it can develop in an epidermoid carcinoma derived of this irritate situation more common in post burn scars and it is known as Marjolin ulcer, in honor of its author in 1828. For these persistent cicatricial ulcers, surgical procedures should be recommended, which would completely extirpate the ulcerated ground that has to be replaced by transplant or graft of skin.

Diseminación intracardiaca de Leiomiomatosis intravenosa: relato de un caso / Intracardiac dissemination of intravenous leiomyomatosis: case perform

Presentamos un caso de un leiomioma uterino primario, histológicamente benigno con metástasis a la vena cava inferior y atrial derecho, en una paciente de 44 años de edad, intervenida con la sospecha de posible mioma uterino. En esta intervención el diagnóstico se transformó en el de masa retroperitoneal, que se biopsió. El resultado histopatológico de la misma fue de fibrosis retroperitoneal idiopática. Se precisó una nueva intervención para el diagnóstico definitivo de leiomiomatosis intravenosa. Revisamos los antecedentes sobre esta entidad rara. Esta condición usualmente no es diagnosticada clínicamente y no es excepcional que ocurra la extensión dentro de la vena cava inferior y hasta la cara derecha del corazón.

We present the case of a histologically benign uterine primary leiomyomata with metastasis to low cava vein and right atrial involvement. The antecedents about this rare entity are reviewed. It was found in a 44 years old patient who was operated for a possible uterine mioma. The histopathological diagnosis revealed an idiopathic retroperitoneal fibrosis. A second operation was performed to obtain a definitive diagnosis of intravenous leiomyomatosis. This condition is not usually clinically diagnosed and it is not uncommon that the extension into the low cava vein or even to the right side of the heart can occur.