Nitric Oxide Plays a Dual Role in Cardiorenal Syndrome in Vitro Model.

BACKGROUND/AIMS: Nitric oxide (NO) plays a dual role, acting as both an oxidant and a reducer, with various effects depending on its concentration and environment. Acute kidney injury's (AKI) pathogenesis observed in cardiorenal syndrome 3 (CRS 3) involves inflammatory responses and the production of reactive oxygen and nitrogen species. However, the role of NO on the development of CRS 3 is still not completely understood. The study aimed to mimic CRS 3 in vitro and investigate NO signaling and inflammatory molecules. METHODS: Thus, HEK293 cells were submitted to normoxia (NX) or hypoxia (HX) protocols for 16 h followed by 3 h of reoxygenation, treated or not with L-NAME. Conditionate medium by HEK293 was transferred to H9c2 for 24 h. Cellular viability was evaluated by MTT assay, real time PCR was used to analyze gene expression and NO content were evaluated in the intra and extracellular medium by amperimetry. RESULTS: Carbonic anhydrase 9 (CA9) expression increased 2.9-fold after hypoxia. Hypoxia reduced 18 % cell viability in HEK293 that was restored by L-NAME treatment. The sum of nitrite (NO2-) and S-nitrosothiol (S-NO) fractions in HEK293 cells showed a substantial decrease on NO intracellular content (38 %). Both IL-6 and IL-10 decreased in all groups compared to NX cells. Besides TNF-α and Bax/Bcl2 ratio increased in hypoxia (approximately 120-fold and 600-fold, respectively) and L-NAME restored this effect. Regarding H9c2 cells, the S-NO fractions showed a substantial decrease in extracellular content after HX (17%) that was not restored by L-NAME. IL-1ß decreases in cardiac cells treated with conditioned medium from HX/L-NAME. CONCLUSION: In conclusion this study highlights the complex interplay of NO and inflammatory factors in hypoxia-induced renal and cardiac cell responses, with potential implications for cardiorenal syndrome.

Progress and Challenges of Understanding Cardiorenal Syndrome Type 3.

The pathologies of the kidney and heart have instigated a large number of researchers around the world to try to better understand what the exact connectors responsible for the emergence and establishment of these diseases are. The classification of these pathologies into different types of cardiorenal syndromes (CRSs) over the last 15 years has greatly contributed to understanding pathophysiological and diagnostic aspects, as well as treatment strategies. However, with the advent of new technologies classified as "Omics", a new range of knowledge and new possibilities have opened up in order to effectively understand the intermediaries between the kidney-heart axis. The universe of micro-RNAs (miRNAs), epigenetic factors, and components present in extracellular vesicles (EVs) have been protagonists in studying different types of CRSs. Thus, the new challenge that is imposed is to select and link the large amount of information generated from the use of large-scale analysis techniques. The present review seeks to present some of the future perspectives related to understanding CRSs, with an emphasis on CRS type 3.

Following Coffee Production from Cherries to Cup: Microbiological and Metabolomic Analysis of Wet Processing of Coffea arabica.

A cup of coffee is the final product of a complex chain of operations. Wet postharvest processing of coffee is one of these operations, which involves a fermentation that inevitably has to be performed on-farm. During wet coffee processing, the interplay between microbial activities and endogenous bean metabolism results in a specific flavor precursor profile of the green coffee beans. Yet, how specific microbial communities and the changing chemical compositions of the beans determine the flavor of a cup of coffee remains underappreciated. Through a multiphasic approach, the establishment of the microbial communities, as well as their prevalence during wet processing of Coffea arabica, was followed at an experimental farm in Ecuador. Also, the metabolites produced by the microorganisms and those of the coffee bean metabolism were monitored to determine their influence on the green coffee bean metabolite profile over time. The results indicated that lactic acid bacteria were prevalent well before the onset of fermentation and that the fermentation duration entailed shifts in their communities. The fermentation duration also affected the compositions of the beans, so that longer-fermented coffee had more notes that are preferred by consumers. As a consequence, researchers and coffee growers should be aware that the flavor of a cup of coffee is determined before as well as during on-farm processing and that under the right conditions, longer fermentation times can be favorable, although the opposite is often believed.IMPORTANCE Coffee needs to undergo a long chain of events to transform from coffee cherries to a beverage. The coffee postharvest processing is one of the key phases that convert the freshly harvested cherries into green coffee beans before roasting and brewing. Among multiple existing processing methods, the wet processing has been usually applied for Arabica coffee and produces decent quality of both green coffee beans and the cup of coffee. In the present case study, wet processing was followed by a multiphasic approach through both microbiological and metabolomic analyses. The impacts of each processing step, especially the fermentation duration, were studied in detail. Distinct changes in microbial ecosystems, processing waters, coffee beans, and sensory quality of the brews were found. Thus, through fine-tuning of the parameters in each step, the microbial diversity and endogenous bean metabolism can be altered during coffee postharvest processing and hence provide potential to improve coffee quality.

Prevalence and Associated Factors to Depression and Anxiety in Women with Premature Babies Hospitalized in a Neonatal Intensive-Care Unit in a Mexican Population.

PURPOSE: The aims of this study were to investigate the frequency of depression and anxiety in mothers of children hospitalized in a neonatal intensive care unit, and to determine the characteristics associated with depression and anxiety in a sample of Mexican mothers. METHOD: We studied 188 mothers who had premature babies in a neonatal intensive-care. Sociodemographic and clinical characteristics were collected through a face to face interview performed by professional staff. We assessed depression using the Beck Depression Inventory (BDI) and clinical anxiety using the Hamilton Anxiety Rating Scale (HAM-A). RESULTS: Clinical anxiety was reported in more than one-third of women (34.0%, n = 64) followed by depression (19.7%, n = 37), while twenty-six women reported both significant depression and anxiety (13.8%). Women with both clinical symptoms were younger, they were more frequently students and were living within extended families. Women who presented only symptoms of depression reported lower educational level (elementary school 29.7%, n = 11). CONCLUSION: Our results show a high incidence of anxiety, depression, and both emotional disorders in Mexican mothers of premature babies hospitalized in a neonatal intensive care unit. Demographic features such as occupation or age may impact the occurrence and severity of joint symptoms of depression and anxiety which should be monitored by the health team and referred to a mental health service.

Renocardiac Effects of p-Cresyl Sulfate Administration in Acute Kidney Injury Induced by Unilateral Ischemia and Reperfusion Injury In Vivo.

The precise mechanisms underlying the cardiovascular complications due to acute kidney injury (AKI) and the retention of uremic toxins like p-cresyl sulfate (PCS) remain incompletely understood. The objective of this study was to evaluate the renocardiac effects of PCS administration in animals subjected to AKI induced by ischemia and reperfusion (IR) injury. C57BL6 mice were subjected to distinct protocols: (i) administration with PCS (20, 40, or 60 mg/L/day) for 15 days and (ii) AKI due to unilateral IR injury associated with PCS administration for 15 days. The 20 mg/L dose of PCS led to a decrease in renal mass, an increase in the gene expression of Cystatin C and kidney injury molecule 1 (KIM-1), and a decrease in the α-actin in the heart. During AKI, PCS increased the renal injury biomarkers compared to control; however, it did not exacerbate these markers. Furthermore, PCS did not enhance the cardiac hypertrophy observed after 15 days of IR. An increase, but not potentialized, in the cardiac levels of interleukin (IL)-1ß and IL-6 in the IR group treated with PCS, as well as in the injured kidney, was also noticed. In short, PCS administration did not intensify kidney injury, inflammation, and cardiac outcomes after AKI.

The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction.

Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with kidney dysfunction and the development of comorbidities in patients with CKD, being only partially eliminated by dialysis therapies. Importantly, drugs used in clinical treatments may affect the levels of uremic toxins, their tissue disposition, and even their elimination through the interaction of both with proteins such as albumin and cell membrane transporters. In this context, protein-bound uremic toxins (PBUTs) are highlighted for their high affinity for albumin, the most abundant serum protein with multiple binding sites and an ability to interact with drugs. Membrane transporters mediate the cellular influx and efflux of various uremic toxins, which may also compete with drugs as substrates, and both may alter transporter activity or expression. Therefore, this review explores the interaction mechanisms between uremic toxins and albumin, as well as membrane transporters, considering their potential relationship with drugs used in clinical practice.

The Gaucher earlier diagnosis consensus point-scoring system (GED-C PSS): Evaluation of a prototype in Finnish Gaucher disease patients and feasibility of screening retrospective electronic health record data for the recognition of potential undiagnosed patients in Finland.

BACKGROUND: Gaucher disease (GD) is a rare inherited multiorgan disorder, yet a diagnosis can be significantly delayed due to a broad spectrum of symptoms and lack of disease awareness. Recently, the prototype of a GD point-scoring system (PSS) was established by the Gaucher Earlier Diagnosis Consensus (GED-C) initiative, and more recently, validated in Gaucher patients in UK. In our study, the original GED-C PSS was tested in Finnish GD patients. Furthermore, the feasibility of point scoring large electronic health record (EHR) data set by data mining to identify potential undiagnosed GD cases was evaluated. METHODS: This biobank study was conducted in collaboration with two Finnish biobanks. Five previously diagnosed Finnish GD patients and ~ 170,000 adult biobank subjects were included in the study. The original PSS was locally adjusted due to data availability issues and applied to the Finnish EHR data representing special health care recordings. RESULTS: All GD patients had high levels of the biomarker lyso-Gb1 and deleterious GBA mutations. One patient was a compound heterozygote with a novel variant, potentially pathogenic mutation. Finnish EHR data allowed the retrospective assessment of 27-30 of the 32 original GED-C signs/co-variables. Total point scores of GD patients were high but variable, 6-18.5 points per patient (based on the available data on 28-29 signs/co-variables per patient). All GD patients had been recorded with anaemia while only three patients had a record of splenomegaly. 0.72% of biobank subjects were assigned at least 6 points but none of these potential "GD suspects" had a point score as high as 18.5. Splenomegaly had been recorded for 0.25% of biobank subjects and was associated with variable point score distribution and co-occurring ICD-10 diagnoses. DISCUSSION: This study provides an indicative GED-C PSS score range for confirmed GD patients, also representing potential mild cases, and demonstrates the feasibility of scoring Finnish EHR data by data mining in order to screen for undiagnosed GD patients. Further prioritisation of the "GD suspects" with more developed algorithms and data-mining approaches is needed. FUNDING: This study was funded by Shire (now part of Takeda).

Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System.

The kidneys and heart share functions with the common goal of maintaining homeostasis. When kidney injury occurs, many compounds, the so-called "uremic retention solutes" or "uremic toxins," accumulate in the circulation targeting other tissues. The accumulation of uremic toxins such as p-cresyl sulfate, indoxyl sulfate and inorganic phosphate leads to a loss of a substantial number of body functions. Although the concept of uremic toxins is dated to the 1960s, the molecular mechanisms capable of leading to renal and cardiovascular injuries are not yet known. Besides, the greatest toxic effects appear to be induced by compounds that are difficult to remove by dialysis. Considering the close relationship between renal and cardiovascular functions, an understanding of the mechanisms involved in the production, clearance and overall impact of uremic toxins is extremely relevant for the understanding of pathologies of the cardiovascular system. Thus, the present study has as main focus to present an extensive review on the impact of uremic toxins in the cardiovascular system, bringing the state of the art on the subject as well as clinical implications related to patient's therapy affected by chronic kidney disease, which represents high mortality of patients with cardiac comorbidities.

Association between reduced quality of life and depression in patients with type 2 diabetes mellitus: a cohort study in a Mexican population.

BACKGROUND: Diabetes mellitus is a chronic disease that requires attention and commitment on the part of patients; improving the quality of life of these patients reduces health costs, morbidity, and mortality. We focused on investigating the factors related with the quality of life and depression symptomatology in patients with type 2 diabetes. PARTICIPANTS AND METHODS: A total of 173 Mexican patients with type 2 diabetes were recruited. An interview face-to-face, a sociodemographic characteristics questionnaire, the Short Form 36 (SF-36), and the Clinical Epidemiological Studies of Depression were applied. The biochemical parameters measured were blood glucose, cholesterol, triacylglycerol levels, and glycated hemoglobin. RESULTS: In all SF-36 subscales, female patients had lower scores in comparison with male patients; individuals ≥65 years of age showed less physical function. We observed that married patients presented a better quality of life than people who were widowed or divorced (P<0.05). Those with high rates of lipids showed decreased scores all the subscales of SF-36. Finally, we observed that depression was the major factor that decreased quality of life in patients with diabetes. CONCLUSION: Our results suggest that untreated and unrecognized depression can decrease the quality of life in patients with diabetes mellitus type 2. Therefore, health care professionals need to consider these findings when treating patients with diabetes. Due to the limited number of patients included in the present study, more studies are needed, studying larger samples in order to provide conclusive results.

Efeito de três semanas de treinamento de flexibilidade no torque e potência muscular de membros inferiores / Three-week effect of stretching training on lower limb torque and muscle power

RESUMO A investigação das possíveis influências entre o treinamento de flexibilidade e o desempenho de força muscular pode contribuir para a compreensão do treinamento. O objetivo do presente estudo foi verificar o efeito de três semanas de treinamento de flexibilidade no torque e potência muscular. Dez adultos, divididos em Grupo Alongamento (GA, N=5) e Controle (GC, N=5) foram avaliados antes e após a intervenção. A intervenção foi realizada pelo GA e consistiu em um protocolo de alongamento estático passivo para os músculos posteriores da coxa, realizados em três por semana e durante três semanas. O torque e potência da extensão e flexão dos joelhos foram avaliados utilizando dinamômetro isocinético em três velocidades (60, 180 e 360º/s). A amplitude de movimento (ADM) foi avaliada pelo teste de sentar e alcançar. Houve incremento de ADM (pré: 23,0±5,6cm; pós: 30,1±6,58cm; p=0,033) do GA, mas não foram observadas diferenças entre e intra-grupos para as demais variáveis (p>0,05). Houveram correlações da ADM apenas para o torque da flexão (r=0,664; p=0,036) e potência da extensão (r=0,638; p=0,047) do joelho esquerdo a 60º/s. Conclui-se que três semanas de treinamento de flexibilidade com método estático passivo promoveu ganhos significativos de ADM, mas não possibilitou incrementos de torque e potência.

ABSTRACT Investigation about influences between stretching training and muscle strength performance can contribute to the understanding of training. The aim of the present study was to verify the effect of three weeks of stretching training on muscle torque and power. Ten adults, divided into Stretching Group (GA, N = 5) and Control Group (CG, N = 5) were evaluated pre and post intervention. The intervention was performed by GA and consisted of a passive static stretching protocol for the posterior thigh muscles, performed three times a week and during three weeks. The torque and power of the knee extension and flexion were evaluated using an isokinetic dynamometer at three speeds (60, 180 and 360º/s). Range of motion (ROM) was assessed using the sit and reach test. There was an increase in ROM (pre: 23.0 ± 5.6 cm; post: 30.1 ± 6.58 cm; p = 0.033) of GA, but there were no differences between and within groups for the other variables (p> 0.05). There were correlations of the ROM only for the flexion torque (r = 0.664; p = 0.036) and power of the extension (r = 0.638; p = 0.047) of the left knee at 60º/s. It was concluded that three weeks of static stretching training promoted significant gains in ROM, but did not allow increases in torque and power.