Body Fluid Retention Research Articles

Sodium-Glucose Cotransporter 2 Inhibitor Combined with Conventional Diuretics Ameliorate Body Fluid Retention without Excessive Plasma Volume Reduction.

We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.

Drug treatment with empagliflozin was beneficial in people with heart failure with preserved ejection fraction: plain language summary of the EMPEROR-Preserved study.

This summary describes a study of a new pill for treating chronic heart failure called empagliflozin (brand name Jardiance®). The study is called EMPEROR-Preserved and was published in the New England Journal of Medicine. Chronic heart failure is a condition where the heart does not pump blood around the body properly. Heart failure causes symptoms such as shortness of breath, tiredness and build-up of too much water in the body (fluid retention). These symptoms often need hospital treatment and increase the risk of early death. The EMPEROR-Preserved study looked at how empagliflozin works in people living with a type of heart failure called heart failure with preserved ejection fraction. In this type of heart failure, the lower left chamber (ventricle) of the heart is too stiff to fill with enough blood during each heartbeat. Almost 6000 people living with preserved ejection fraction heart failure were asked to take either a pill containing empagliflozin or a placebo, an identical pill lacking empagliflozin, daily. The choice of pill for each participant was randomly assigned. The study was double-blinded, meaning that neither the participants nor their doctors knew which pill the participants were taking. After an average of 26months of treatment, empagliflozin reduced the risk of participants needing hospital treatment for complications of heart failure by about 30%. Side effects were generally similar in participants who took empagliflozin and in those who took the placebo, except for genital infections like thrush, which happened in more people who took empagliflozin (2.2%) than in those who took the placebo (0.7%). A previous study called EMPEROR-Reduced found that empagliflozin had similar benefits in participants with heart failure with reduced ejection fraction. Therefore, the overall evidence shows that empagliflozin can help people with heart failure whether it is caused by reduced ejection fraction or preserved ejection fraction. Clinical Trial Registration: NCT03057951 (EMPEROR-Preserved study) (ClinicalTrials.gov).

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study.

This is a summary of the article describing the EMPEROR-Reduced study of empagliflozin, which was published in the New England Journal of Medicine. Empagliflozin (brand name Jardiance®) is a new drug therapy for the treatment of chronic heart failure. Chronic heart failure is a long-term condition where the heart cannot pump enough blood around the body, leading to symptoms such as shortness of breath, fatigue and build-up of too much water in the body (fluid retention). It also increases the risk for premature death. The EMPEROR-Reduced study looked at the effects of empagliflozin, a medication taken once daily, in people with reduced ejection fraction. This is a type of heart failure where insufficient blood is pushed out of the heart muscle as it contracts. The study was conducted because more evidence is needed on the effects of empagliflozin and similar drugs in people with heart failure, including those with reduced ejection fraction. The main aim of the EMPEROR-Reduced study was to see if empagliflozin reduces the risk of being taken to hospital for complications of heart failure or dying from heart disease. Over 3700 people with heart failure and reduced ejection fraction were randomly given either empagliflozin or placebo (an identical pill lacking medication) daily for about 16months. This was a double-blind study, which means that neither the participants nor the researchers knew which treatment participants were receiving. After an average of 16months of continuous treatment, fewer patients taking empagliflozin (13.2%) needed to be hospitalized for complications of heart failure than those taking placebo (18.3%). Also, fewer patients taking empagliflozin (1.6%) developed serious kidney problems than those taking placebo (3.1%). Side effects were generally similar in participants who received empagliflozin and those who received placebo, except for genital tract infections, which affected more participants who received empagliflozin (1.7%) than placebo (0.6%). This study suggests that people with chronic heart failure with reduced ejection fraction may benefit from treatment with empagliflozin, mainly by needing to go to hospital less often because of complications of heart failure. Clinical Trial Registration: NCT03057977 (EMPEROR-Reduced study) (ClinicalTrials.gov).

PS-BPB10-1: INVOLVEMENT OF RENAL TUBULAR NFAT5 IN THE REGULATION OF BLOOD PRESSURE AND BODY FLUID VOLUME

Objective: Nuclear factor of activated T-cells 5 (NFAT5) is an osmoresponsive transcription factor that activates osmoprotective genes to protect cells against hypertonicity. Renal tubular cell-specific NFAT5 knockout (KO) mice have been shown to exhibit polyuria, hypernatremia, low urinary sodium excretion, and increased expression of the epithelial sodium channel (ENaC) in the kidney. In the present study, regulation of blood pressure (BP) as well as that of body fluid volume were examined in the wild type (WT) mice and NFAT5 KO mice. Methods: The BP of KO mice and WT mice was measured using radiotelemetry method. The mice were fed with regular salt diet (RSD, 0.3% NaCl chow) or high salt diet (HSD, 8% NaCl chow) followed by the treatment with amiloride, an ENaC blocker. To assess body fluid volume, the plasma renin activity (PRA) and the plasma aldosterone concentration (PAC) were measured at the condition of RSD and HSD, together with plasma arginine vasopressin (AVP) and hematocrit (Ht) levels. Results: Compared to WT mice, the mean BP was significantly higher in KO mice both at the condition with RSD and that with HSD in dark period, but not in light period. Treatment with amiloride significantly decreased the mean BP in KO mice with HSD to the level of WT mice with HSD in dark period. PRA, PAC, and AVP levels were not significantly different between in WT and KO mice with RSD. HSD significantly decreased PRA and PAC and tended to increase the AVP level both in WT and KO mice. The Ht level was significantly lower in KO mice than in WT mice regardless of RSD or HSD (WT with RSD, 42.6 ± 0.5%; WT with HSD, 42.8 ± 0.6%; KO with RSD, 38.3 ± 0.4%; KO with HSD, 39.0 ± 0.4%, n = 4). Conclusions: The results suggest that the renal tubular cell-specific NFAT5 KO mice exhibit excess body fluid retention induced by sodium reabsorption through ENaC, leading to salt-sensitive hypertension. Such phenotypes seem to be independent of the systemic renin-angiotensin-aldosterone and AVP systems. Renal tubular NFAT5 could integrate urine concentration and sodium reabsorption in the kidney, thus preventing salt-dependent hypertension.

Metabolites of endophytic fungi isolated from leaves of Bauhinia variegata exhibit antioxidant activity and agonist activity on peroxisome proliferator-activated receptors α, β/δ and γ.

Diabetes mellitus is a metabolic disorder that affects millions of people worldwide and is linked to oxidative stress and inflammation. Thiazolidinediones (TZD) improve insulin sensitization and glucose homeostasis mediated by the activation of peroxisome proliferator-activated receptors γ (PPARγ) in patients with type 2 diabetes. However, their use is associated with severe adverse effects such as loss of bone mass, retention of body fluids, liver and heart problems, and increased risk of bladder cancer. Partial PPARγ agonists can promote the beneficial effects of thiazolidinediones with fewer adverse effects. Endophytic fungi colonize plant tissues and have a particularly active metabolism caused by the interaction with them, which leads to the production of natural products with significant biological effects that may be like that of the colonized plant. Here, we identify seven endophytic fungi isolated from Bauhinia variegata leaves that have antioxidant activities. Also, one of the extracts presented pan-agonist activity on PPAR, and another showed activity in PPARα and PPARβ/δ. A better understanding of this relationship could help to comprehend the mechanism of action of antioxidants in treating diabetes and its complications. Moreover, compounds with these capabilities to reduce oxidative stress and activate the receptor that promotes glucose homeostasis are promising candidates in treatment of diabetes.

The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus.

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin's osmotic diuresis mechanism, patients' serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=-0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e' tended to decrease (β1=-0.382, p=0.13, LRA). Compared to the baseline, E/e' was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e' group (E/e'≥10, n=34), E/e' decreased significantly (β1=-0.63, p<0.05, LRA). ΔE/e' was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e' in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function.

Corin: A Key Mediator in Sodium Homeostasis, Vascular Remodeling, and Heart Failure

Simple SummaryAtrial natriuretic peptide (ANP) is an important hormone that regulates many physiological and pathological processes, including electrolyte and body fluid balance, blood volume and pressure, cardiac channel activity and function, inflammatory response, lipid metabolism, and vascular remodeling. Corin is a transmembrane serine protease that activates ANP. Variants in the CORIN gene are associated with cardiovascular disease, including hypertension, cardiac hypertrophy, atrial fibrillation, heart failure, and preeclampsia. The current data indicate a key role of corin-mediated ANP production and signaling in the maintenance of cardiovascular homeostasis. In this review, we discuss the latest findings regarding the molecular and cellular mechanisms underlying the role of corin in sodium homeostasis, uterine spiral artery remodeling, and heart failure.Atrial natriuretic peptide (ANP) is a crucial element of the cardiac endocrine function that promotes natriuresis, diuresis, and vasodilation, thereby protecting normal blood pressure and cardiac function. Corin is a type II transmembrane serine protease that is highly expressed in the heart, where it converts the ANP precursor to mature ANP. Corin deficiency prevents ANP activation and causes hypertension and heart disease. In addition to the heart, corin is expressed in other tissues, including those of the kidney, skin, and uterus, where corin-mediated ANP production and signaling act locally to promote sodium excretion and vascular remodeling. These results indicate that corin and ANP function in many tissues via endocrine and autocrine mechanisms. In heart failure patients, impaired natriuretic peptide processing is a common pathological mechanism that contributes to sodium and body fluid retention. In this review, we discuss most recent findings regarding the role of corin in non-cardiac tissues, including the kidney and skin, in regulating sodium homeostasis and body fluid excretion. Moreover, we describe the molecular mechanisms underlying corin and ANP function in supporting orderly cellular events in uterine spiral artery remodeling. Finally, we assess the potential of corin-based approaches to enhance natriuretic peptide production and activity as a treatment of heart failure.

Comparison of Three Clinical Trials of Preoperative Predictors for Complicated Appendicitis.

We previously reported three items that preoperatively predicted complicated appendicitis (body temperature, C-reactive protein, and fluid retention around the appendix). In this study, we aimed to compare other predictors to confirm the usefulness of our predictors with those of previous reports on the items as predictors of complicated appendicitis preoperatively (criteria A which consist of 8 items, criteria B which consist of 7 items). We retrospectively evaluated 417 adult patients who underwent surgery for acute appendicitis between January 2013 and December 2019 and compared our items with criteria A and criteria B according to the results of the area under the receiver operating characteristic curve (AUC), homogeneity, discriminatory ability, and Akaike information criterion (AIC). The AUC for the sensitivity to diagnose complicated appendicitis according to according to our criteria, as well as criteria A, and criteria B was 0.823, 0.839, and 0.856, respectively. The discriminatory ability linear trend χ2 of our criteria and those of criteria A and B were 128.9, 121.1, and 142.5, respectively. The homogeneity likelihood ratios χ2 calculated using the Cox regression model, which indicate homogeneity, were 146.4, 143.6, and 172.8, respectively. The AIC of each criterion was 397.0, 345.8, and 369.0, respectively. Although the criteria B were the best, it was possible to predict complicated appendicitis preoperatively by all criteria. Above all, our criteria have only three items, therefore they have the advantage of making it possible to make decisions quickly with a certain degree of accuracy, regardless of the degree of experience.

Physical activity, sedentary behaviour and incidence of obstructive sleep apnoea in three prospective US cohorts.

Reduced physical activity and increased sedentary behaviour may independently contribute to the development of obstructive sleep apnoea (OSA) through increased adiposity, inflammation, insulin resistance and body fluid retention. However, epidemiological evidence remains sparse and is primarily limited to cross-sectional studies. We prospectively followed 50 332 women from the Nurses' Health Study (2002-2012), 68 265 women from the Nurses' Health Study II (1995-2013) and 19 320 men from the Health Professionals Follow-up Study (1996-2012). Recreational physical activity (quantified by metabolic equivalent of task (MET)-h per week) and sitting time spent watching TV and at work/away from home were assessed by questionnaires every 2-4 years. Physician-diagnosed OSA was identified by validated self-report. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals for OSA incidence associated with physical activity and sedentary behaviour. During 2 004 663 person-years of follow-up, we documented 8733 incident OSA cases. After adjusting for potential confounders, the pooled HR for OSA comparing participants with ≥36.0 versus <6.0 MET-h per week of physical activity was 0.46 (95% CI 0.43-0.50; ptrend<0.001). Compared with participants spending <4.0 h per week sitting watching TV, the multivariable-adjusted HR was 1.78 (95% CI 1.60-1.98) for participants spending ≥28.0 h per week (ptrend<0.001). The comparable HR was 1.49 (95% CI 1.38-1.62) for sitting hours at work/away from home (ptrend<0.001). With additional adjustment for several metabolic factors, including body mass index and waist circumference, the associations with physical activity and sitting hours at work/away from home were attenuated but remained significant (ptrend<0.001), whereas the association with sitting hours watching TV was no longer statistically significant (ptrend=0.18). Higher levels of physical activity and fewer sedentary hours were associated with lower OSA incidence. The potential mediating role of metabolic factors in the association between sedentary behaviour and OSA incidence may depend on the type of sedentary behaviour. Our results suggest that promoting an active lifestyle may reduce OSA incidence.

Counterpoint: Investigators should not control for menstrual cycle phase when performing studies of vascular control that include women.

Observed sex differences in the epidemiology of cardiovascular disease incidence and the efficacy of clinical intervention strategies, coupled with recent mandates from the National Institutes of Health (NIH), and its international counterparts to consider sex as a biological variable in all preclinical and clinical work (15), have led to increased enrollment of women in human physiology studies of vascular function with the goal of improving external validity and clinical applicability of the findings. However, standard practice in these studies is to test women during the early follicular phase (~days 1-5) of the menstrual cycle, during which estrogen and progesterone concentrations are lowest, and either exclude or limit testing of women who use hormonal contraceptives to the placebo phase. This approach seeks to control for, or limit, differences in circulating hormone concentrations between men and women and is based on the dogmatic theory that cyclic changes in estrogen and progesterone concentrations lead to greater variability in study outcomes and uninterpretable datasets. Contrary to this common approach, we propose that limiting testing of women to this single phase 1) decreases external validity of the findings, 2) obfuscates potential physiological differences contributable to differences in sex hormone concentrations between men and women, and 3) is, in many instances, contradicted by literature that demonstrates limited or no variability in vascular measurements across the menstrual cycle.

Antidiabetic Therapy in the Treatment of Nonalcoholic Steatohepatitis.

Liver-related diseases are the third-leading causes (9.3%) of mortality in type 2 diabetes (T2D) in Japan. T2D is closely associated with nonalcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. No pharmacotherapies are established for NASH patients with T2D. Though vitamin E is established as a first-line agent for NASH without T2D, its efficacy for NASH with T2D recently failed to be proven. The effects of pioglitazone on NASH histology with T2D have extensively been established, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH and NAFLD (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin has already entered the phase 3 trial (DEAN study). A key clinical need is to determine the kinds of antidiabetic drugs that are the most appropriate for the treatment of NASH to prevent the progression of hepatic fibrosis, resulting in HCC or liver-related mortality without increasing the risk of cardiovascular or renal events. Combination therapies, such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide/GLP-1, are under development. This review focused on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2D.

Hepatoprotective Effect of SGLT2 Inhibitor on Nonalcoholic Fatty Liver Disease

A fourth of the adult population is now suffering from nonalcoholic fatty liver disease (NAFLD) worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to liver-related mortality. NAFLD/NASH is closely associated with type 2 diabetes. Although pioglitazone is now recommended as the 1st line therapy for NASH with type 2 diabetes, pioglitazone has several safety concerns such as body weight gain, heart failure, fluid retention, and bone fracture in women. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have a variety of functions such as glycemic control, bodyweight reduction, and decreased body pressure. Accumulating evidence has shown that this agent has also cardioprotective and renoprotective effects in patients with or without type 2 diabetes. Recent studies that SGLT2 inhibitor can also reduce in transaminase activities or hepatic fat content in NAFLD. NAFLD patients with type 2 diabetes can be indicated for SGLT2 inhibitor, because they are obese, have insulin resistance, and at high risk of cardiovascular events. The phase 3 study of dapagliflozin for NAFLD (DEAN study) is now ongoing. It remains unknown whether this agent can ameliorate hepatic fibrosis in NASH, leading to improved over-all or liver-related survival. Since the leading cause of NAFLD mortality is cardiovascular events, SGLT2 inhibitors will become the 1st line treatment for NAFLD/NASH.

Impact of serum albumin levels on the body fluid response to tolvaptan in chronic kidney disease patients.

Tolvaptan exerts an aquaretic effect by blocking vasopressin V2 receptor. Although tolvaptan ameliorates body fluid retention even in patients with chronic kidney disease (CKD), predictors of body fluid reduction induced by tolvaptan remain unclear. We, therefore, examined the clinical parameters associated with the effect of tolvaptan on fluid volume in CKD patients. Twelve CKD patients (stage 3-5) with fluid retention were treated with tolvaptan in addition to conventional diuretic treatment. Patients were divided into low and high responders by the median change in total body water (TBW) for 1week measured by a bioimpedance analysis (BIA) device, and clinical parameters were compared between the groups. The body weight significantly decreased by 2.0 ± 2.3kg (p = 0.005), but the estimated glomerular filtration rate (eGFR) was not significantly changed (16.9 ± 11.9 vs. 17.4 ± 12.4mL/min/1.73m2, p = 0.139) after 1week. The BIA showed that the intracellular water (ICW) decreased by 6.0% ± 4.7% (p < 0.001), the extracellular water (ECW) decreased by 6.7% ± 5.4% (p = 0.001), and the TBW decreased by 6.3% ± 4.9% (median value - 6.02%, p < 0.001). The serum albumin level in the high responders was significantly lower than in the low responders (2.3 ± 0.5 vs. 3.3 ± 0.8g/dL, p = 0.013). Significant partial correlations adjusted for the eGFR were observed between the baseline serum albumin level and changes in the ICW (r = 0.440, p = 0.048), ECW (r = 0.593, p = 0.009) and TBW (r = 0.520, p = 0.020). Serum albumin levels predict the body fluid response to tolvaptan in CKD patients. Tolvaptan may be a promising therapeutic option for ameliorating body fluid retention, especially in patients with hypoalbuminemia.

Effect of tolvaptan on the prognosis of patients with hepatic ascites.

Despite accumulating evidence concerning the efficacy of tolvaptan in the treatment of body fluid retention or hyponatremia, the effect of tolvaptan on the prognosis of patients with hepatic ascites has not been fully investigated. A total of 628 patients with hepatic ascites who were treated with diuretics (furosemide, spironolactone, or tolvaptan) between 2007 and 2017 were enrolled and divided into two groups: those who received tolvaptan (original tolvaptan group, n = 278) and those who did not (original control group, n = 350). The cumulative survival rates between the groups were compared and the factors associated with survival in patients with hepatic ascites were identified using a Cox regression analysis. In addition, propensity score matching was applied in patients who started conventional diuretics for new-onset hepatic ascites after September 2013 (pre-matching tolvaptan group, n = 177; pre-matching control group, n = 63), and the cumulative survival rates were compared between the post-matching tolvaptan and control groups. The survival rate was significantly higher in the tolvaptan group than the control group (P = 0.005), and tolvaptan therapy was identified as an independent factor associated with survival (hazard ratio 0.721 for death relative to control, P < 0.001). The propensity score-matched comparison also showed a significantly higher survival rate in the tolvaptan group (n = 51) than in the control group (n = 51) (P = 0.009). This study suggests that tolvaptan might improve the prognosis of patients with hepatic ascites.

Seven-Day Salt Loading Impairs Microvascular Endothelium-Dependent Vasodilation without Changes in Blood Pressure, Body Composition and Fluid Status in Healthy Young Humans

Objectives: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium-dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure (BP), and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. Materials and Methods: Fifty-three young healthy individuals (28 women and 25 men) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day). Skin microvascular blood flow in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed by laser Doppler flowmetry, and BP, heart rate (HR), plasma renin activity (PRA), serum aldosterone, serum and 24 h-urine sodium, potassium, urea and creatinine levels, together with body composition and fluid status measurement with a 4-terminal portable impedance analyzer were measured before and after diet protocols. Results: BP, HR, body composition and fluid status were unchanged, and PRA and serum aldosterone level were significantly suppressed after HS diet. ACh-induced dilation (AChID) was significantly impaired, while SNP-induced dilation was not affected by HS diet. Impaired AChID and increased salt intake, as well as impaired AChID and suppressed renin-angiotensin system were significantly positively correlated. Changes in body composition and fluid status parameters were not associated with impaired AChID. Conclusion: 7-day HS diet impairs microvascular reactivity by affecting its endothelium-dependent vasodilation in young healthy individuals. Changes are independent of BP, body composition changes or fluid retention, but are the consequences of the unique effect of HS on endothelial function.

Simulation and experimental investigations into abrasive flow nanofinishing of surgical stainless steel tubes

ABSTRACTSurface roughness is one of the critical properties that affect the performance of biomedical devices and human implant's functions. Higher surface roughness leads to the comparatively higher probability of body fluid retention in the surface valleys. Surface roughness peaks can easily obstruct the flow of body fluid and drug. Abrasive flow finishing (AFF) is an advanced finishing process, which can produce nano-level surface finish in complex components. In this paper, experimental investigations, including parametric study on nanofinishing of surgical stainless steel 316L tubes using AFF process has been reported. Indigenous multiple polymers blended base medium was developed to perform the nanofinishing experiments. Based on the experimental results, statistical model has been presented. To understand the AFF process in depth, finite element approach has been implemented to determine the finishing forces generated during the AFF experiments. Initial surface roughness on the internal surface of the workpiece varies in the range of (0.67–0.50) µm. The best surface finish of 48 nm with a percent improvement (% ΔRa) of 92.20% has been achieved after processing the workpiece with AFF process. Simulated results are validated with the experimental results and the deviations are in the acceptable range.

Novel antidiabetic medications for non-alcoholic fatty liver disease with type 2 diabetes mellitus.

Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM. Although metformin is established as the first-line therapy for T2DM, given its relative safety and beneficial effects on glycosylated hemoglobin, weight, and cardiovascular mortality, this agent is not recommended as specific therapy for NASH/NAFLD due to lack of clinical evidence. The effects of pioglitazone on NASH histology with T2DM have been extensively proved, but several concerns exist, such as body weight gain, fluid retention, cancer incidence, and bone fracture. In recent years, novel antidiabetic medications have been approved for T2DM, such as glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and sodium/glucose cotransporter 2 inhibitors. A key clinical question for hepatologists is what kinds of antidiabetic medications are the most appropriate for the treatment of NAFLD accompanied by T2DM, to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increased risk of cardiovascular events. This review focuses on novel antidiabetic agents and future perspectives on the treatment of NAFLD/NASH with T2DM.

B-type natriuretic peptide is a determinant of the nocturnal increase in blood pressure independently of arterial hypertrophy and hypoxia.

Loss of the nocturnal blood pressure (BP) drop is a risk factor for cardiovascular outcomes. However, clinical parameters that predispose to changes in nocturnal BP are currently uncertain. Given the possible involvement of salt sensitivity in nocturnal BP levels, we investigated a hypothesized association between plasma B-type natriuretic peptide (BNP) levels - a marker of body fluid retention - and nocturnal BP in a general population. Study participants were 1020 general individuals. Participants were divided into four groups (riser, nondipper, dipper, and extreme dipper) by their percentage changes in nocturnal SBP measured using an ambulatory BP monitor. Plasma BNP levels were positively associated with circadian BP change (β = 0.162, P < 0.001) independently of carotid hypertrophy (β = 0.133, P < 0.001), and awake heart rate (β = -0.102, P = 0.001) and SBP (β = -0.246, P < 0.001). Risers showed 1.6 times higher BNP levels than dippers, whereas oxygen desaturation during sleep was frequently observed in nondippers. Results of multinomial logistic regression analysis indicated that BNP level was a significant determinant for the riser pattern [odds ratio (OR) 1.27 (BNP 10 pg/ml), P < 0.001], whereas oxygen desaturation was specifically associated with the nondipping pattern (OR 1.04, P = 0.001). When participants were subdivided by BNP level, risers were more frequent in the high BNP subgroup (19.5%) than in the low BNP subgroup (6.7%) (OR 3.39, P < 0.001). A slight increase in plasma BNP level was independently associated with rising nocturnal BP. Our results may help to understand the pathophysiology of circadian BP variation, and be a clue to identify individuals who require careful BP monitoring.

Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review.

The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin.

Camera on Vessel: A Camera-Based System to Measure Change in Water Volume in a Drinking Glass.

A major problem related to chronic health is patients’ “compliance” with new lifestyle changes, medical prescriptions, recommendations, or restrictions. Heart-failure and hemodialysis patients are usually placed on fluid restrictions due to their hemodynamic status. A holistic approach to managing fluid imbalance will incorporate the monitoring of salt-water intake, body-fluid retention, and fluid excretion in order to provide effective intervention at an early stage. Such an approach creates a need to develop a smart device that can monitor the drinking activities of the patient. This paper employs an empirical approach to infer the real water level in a conically shapped glass and the volume difference due to changes in water level. The method uses a low-resolution miniaturized camera to obtain images using an Arduino microcontroller. The images are processed in MATLAB. Conventional segmentation techniques (such as a Sobel filter to obtain a binary image) are applied to extract the level gradient, and an ellipsoidal fitting helps to estimate the size of the cup. The fitting (using least-squares criterion) between derived measurements in pixel and the real measurements shows a low covariance between the estimated measurement and the mean. The correlation between the estimated results to ground truth produced a variation of 3% from the mean.