Acid Excretion Rate Research Articles

Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia.

Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects. This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism. The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western Blotting. According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. In vivo, activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels. Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury.

Skeletal muscle mass and function are affected by pancreatic atrophy, pancreatic exocrine insufficiency and poor nutritional status in patients with chronic pancreatitis

Background/ObjectivePrevious studies have demonstrated that sarcopenia is frequently observed in patients with chronic pancreatitis (CP). However, most studies have defined sarcopenia solely based on skeletal muscle (SM) loss, and muscle weakness such as grip strength (GS) reduction has not been considered. We aimed to clarify whether SM loss and reduced GS have different associations with clinical characteristics and pancreatic imaging findings in patients with CP. MethodsOne hundred two patients with CP were enrolled. We defined SM loss by the SM index at the third lumbar vertebra on CT (<42 cm2/m2 for males and <38 cm2/m2 for females), and reduced GS by < 28 kg for males and <18 kg for females. ResultsFifty-seven (55.9 %) patients had SM loss, 21 (20.6 %) had reduced GS, and 17 (16.7 %) had both. Patients with SM loss had lower body mass index, weaker GS, higher Controlling Nutritional Status score, lower serum lipase level, and lower urinary para-aminobenzoic acid excretion rate, suggesting worse nutritional status and pancreatic exocrine insufficiency. On CT, main pancreatic duct dilatation and parenchymal atrophy were more frequent in patients with SM loss than in those without it. Patients with reduced GS were older and had worse nutritional status than those without it. ConclusionsSM loss was associated with pancreatic exocrine insufficiency, low nutritional status, and pancreatic imaging findings such as parenchymal atrophy and main pancreatic duct dilatation, whereas older age and low nutritional status led to additional reduced GS.

Sodium-Glucose Cotransporter 2 Inhibitors to Decrease the Uric Acid Concentration-A Novel Mechanism of Action.

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are glucose-lowering agents whose positive impact on cardiovascular risk has been described extensively. Not only do they influence lipid profile, blood pressure, atherosclerosis risk, hemoglobin level, and insulin resistance, but they also reduce cardiovascular events, all-cause mortality, and hospitalization rates. Some of these effects may be due to their impact on serum uric acid (SUA) concentration. Findings from nine meta-analyses showed that, indeed, SGLT2is significantly reduce SUA. The data on the drug- and dose-dependency of this effect were inconclusive. Several factors alternating the beneficial effects of SGLT2is on SUA, such as glycated hemoglobin concentration (HbA1c), presence of diabetes, and baseline SUA level, were described. Even though there is a consensus that the lowering of SUA by SGLT2is might be due to the increased urinary excretion rate of uric acid (UEUA) rather than its altered metabolism, the exact mechanism remains unknown. The influence of SGLT2is on SUA may not only be used in gout treatment but may also be of huge importance in explaining the observed pleiotropic effects of SGLT2is.

Emodin, a Natural Anthraquinone, Increases Uric Acid Excretion in Rats with Potassium Oxonate-Induced Hyperuricemia.

The treatment of hyperuricemia and gout is mostly based on lowering serum uric acid levels using drugs, such as allopurinol, or increasing urinary excretion of uric acid. However, some patients still experience adverse reactions to allopurinol and turn to Chinese medicine as an alternative. Therefore, it is crucial to design a preclinical study to obtain more convincing data on the treatment of hyperuricemia and gout with Chinese medicine. This study aimed to explore the therapeutic effect of emodin, a Chinese herbal extract, in a rat model of hyperuricemia and gout. In this study, we used 36 Sprague-Dawley rats, which were randomly divided into six groups for experimentation. Hyperuricemia was induced in rats by intraperitoneal injections of potassium oxonate. The efficacy of emodin in reducing serum uric acid levels was demonstrated by comparing the positive control group with groups treated with three different concentrations of emodin. The inflammatory profiles, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels, were unaffected by emodin treatment. In the experimental results, it was observed that the serum uric acid concentration in the vehicle control group was 1.80 ± 1.14, while the concentrations in the moderate and high concentration emodin groups were 1.18 ± 0.23 and 1.12 ± 0.57, resulting in no significant difference in uric acid concentration between these treatment groups and the control group, indicating that emodin has a therapeutic effect on hyperuricemia. The increase in the fractional excretion of uric acid (FEUA) demonstrated that emodin promoted urinary uric acid excretion without significantly affecting the inflammatory profile. Thus, emodin reduced the serum uric acid concentration to achieve effective treatment of hyperuricemia and gout by increasing urinary excretion. These results were supported by the measured serum uric acid and FEUA levels. Our data have potential implications for the treatment of gout and other types of hyperuricemia in clinical practice.

MP10-03 INFLUENCE OF SGLT2 INHIBITORS ON 24-HOUR URINE PARAMETERS AMONG KIDNEY STONE PATIENTS IN THE MEDICARE POPULATION

You have accessJournal of UrologyCME1 Apr 2023MP10-03 INFLUENCE OF SGLT2 INHIBITORS ON 24-HOUR URINE PARAMETERS AMONG KIDNEY STONE PATIENTS IN THE MEDICARE POPULATION Joseph Crivelli, Ryan Hsi, Mary Oerline, John Asplin, Naim Maalouf, and John M Hollingsworth Joseph CrivelliJoseph Crivelli More articles by this author , Ryan HsiRyan Hsi More articles by this author , Mary OerlineMary Oerline More articles by this author , John AsplinJohn Asplin More articles by this author , Naim MaaloufNaim Maalouf More articles by this author , and John M HollingsworthJohn M Hollingsworth More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Sodium/glucose cotransporter 2 inhibitors (SGLT2is) are widely used for patients with type 2 diabetes. Recent epidemiologic studies have shown a reduction in stone events in diabetic patients treated with SGLT2is, but changes in urine chemistries that may account for this have not been identified. The purpose of this study was to evaluate the effect of SGLT2is on urine chemistry and supersaturation among patients with kidney stone disease. METHODS: From a Medicare-Litholink database (years 2010-2018), we identified patients who received two, 24-hour urine tests, of which the first was performed without SGLT2i use, and the second was collected during SGLT2i use. Patients were excluded if they started using alkali citrate, thiazide, or xanthine oxidase inhibitor between the two collections, and excluded if the creatinine excretions in the 2 collections differed by >30%. Bivariate comparisons using the t-test were compared between 24-hour urine variables with p<0.05 considered statistically significant. RESULTS: Among 30 patients identified, the cohort had mean±SD age 66.6±8.9 years, 80% were male, and all with Medicare Part A/B available information (n=24) had a baseline diagnosis of diabetes mellitus type 2. The SGLT2i used included canagliflozin (in 56.7%), dapagliflozin (20.0%), and empagliflozin (23.3%). The mean±SD time from the first to second collection was 18.5±17.4 months. Comparison of 24-hour parameters between the first collection (pre-SGLT2i) and the second collection (on SGLT2i) is shown in the Table 1. Notable findings include a trend to higher 24-hour urine volume by 0.38 L/day (p=0.065), and significantly lower urine pH (p=0.046), with non-significant changes in urine excretion rate of calcium, oxalate, citrate, uric acid, and phosphorus. This resulted in a significant reduction in urine supersaturation with respect to calcium phosphate (likely from combination of greater urine volume and slightly lower pH), but non-significant changes in SS calcium oxalate and uric acid. CONCLUSIONS: Chronic SGLT2i use is associated with a lower urine pH with non-significant changes in volume and the excretion of major stone-related electrolytes. Larger studies are needed to confirm these findings and explore the impact of SGLT2i on stone recurrence rate. Source of Funding: Supported by National Institutes of Health Grant 1R01DK121709 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e114 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joseph Crivelli More articles by this author Ryan Hsi More articles by this author Mary Oerline More articles by this author John Asplin More articles by this author Naim Maalouf More articles by this author John M Hollingsworth More articles by this author Expand All Advertisement PDF downloadLoading ...

Carnitine affects Octanoate Oxidation to Carbon Dioxide and Dicarboxylic Acids in Colostrum-Deprived Piglets: In Vivo Analysis of Mechanisms Involved Based on CoA- and Carnitine-Ester Profiles

Newborn, colostrum-deprived piglets (n = 21) were used to study the effects of L-carnitine supplementation on the in vivo oxidation of [1-14C]octanoate to CO2 and dicarboxylic acids. Pigs were fitted with arterial and bladder catheters and were infused with octanoate (supplying 35–100% of piglets' energy expenditure) and with or without valproate for a period of 24 h. After achieving steady-state octanoate oxidation, carnitine was coinfused [50 µmol/kg0.75 prime plus 20 µmol/(h·kg0.75)], and deviations in the octanoate oxidation rate, dicarboxylic acid excretion rate, and carnitine metabolism were monitored. At the end of the 24-h infusion, samples of liver and muscle were analyzed for carnitine- and CoA-esters by HPLC. Carnitine stimulated octanoate oxidation by 7% (P < 0.05) and decreased dicarboxylic acid excretion by 45% (P < 0.05). Carnitine supplementation increased (P < 0.05) concentrations of carnitine and acetyl carnitine in hepatic tissue (three- and 55-fold, respectively) and plasma (seven- and 11-fold); whereas, muscle-carnitine concentration doubled upon carnitine supplementation, but acetyl carnitine concentration remained unaltered. Urinary excretion of acetyl and free carnitine also increased with carnitine supplementation, but accounted for <10% of carnitine infused. Hepatic total CoA and CoA esters increased with carnitine supplementation, whereas muscle acetyl-CoA decreased. Valproate had only marginal effects on octanoate metabolism. These data confirm the hypothesis that carnitine affects the in vivo oxidation of octanoate in colostrum-deprived piglets and suggest that the effects may be mediated by aiding the export of excess acetyl groups from muscle or by enhancing uptake of octanoate into liver mitochondria.

The association of urinary prostaglandins with uric acid in hyperuricemia patients

PurposeTo explore the association between uric acid and urinary prostaglandins in male patients with hyperuricemia.MethodsA total of 38 male patients with hyperuricemia in outpatients of Huadong Hospital from July 2018 to January 2020 were recruited. Serum uric acid (SUA), 24 h urinary uric acid excretion and other indicators were detected respectively. 10 ml urine was taken to determine prostaglandin prostaglandin D (PGD), prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), 6-keto-PGF1α, thromboxane A2 (TXA2) and thromboxane B2 (TXB2). Fraction of uric acid excretion (FEua) and uric acid clearance rate (Cua) were calculated. According to the mean value of FEua and Cua, patients were divided into two groups, respectively. The independent-samples t test and the Mann–Whitney U test were applied for normally and non-normally distributed data, respectively.ResultsAfter adjusting confounding factors (age, BMI, eGFR, TG, TC, HDL and LDL), SUA was negatively correlated with urinary PGE1(r = -0.615, P = 0.009) and PGE2(r = -0.824, P < 0.001). Compared with SUA1 group (SUA < 482.6 mg/dl), SUA2 (SUA ge 482.6 mg/dl) had lower urinary PGE1(P = 0.022) and PGE2(P = 0.019) levels. Cua was positively correlated with PGE2 (r = 0.436, P = 0.01). The correlation persisted after adjustment for age, BMI, eGFR, TG, TC, HDL and LDL by multiple linear regression analysis. In the Cua1 group (Cua < 4.869 mL /min/1.73 m2), PGE2 were lower than that in Cua2 (Cua ge 4.869 mL /min/1.73 m2) group (P = 0.011).ConclusionsIn male patients with hyperuricemia, SUA was negatively correlated with urinary PGE2, Cua was positively correlated with urinary PGE2. Urinary PGE2 were significantly different between different SUA and Cua groups.

Excretion of oxidated cortisol metabolites is markedly lower than previously assumed: An analysis of urinary cortoic acids in healthy children by GC–MS

Discovered about 50 years ago, the four C21 steroidal acids (α-)cortolic acid, β-cortolic acid, (α‑)cortolonic acid and β-cortolonic acid present the oxidative end products of cortisol metabolism. Undergoing renal elimination, these cortoic acids have been assumed to constitute up to 25 % of total urinary cortisol metabolites. However, their analysis has been difficult, only few data has been published in adults, and this class of steroids has become practically forgotten. Since data in children are lacking and nothing is known about their metabolism during human development, we aimed at establishing a more practical analytical method and determined their urinary concentrations in a high number of healthy subjects. In our method, 5-mL-aliquots of 24-hour urine samples were subjected to solid phase extraction (C18 cartridges), followed by strong anion exchange chromatography, and formation of 2-propylester-trimethylsilylether derivatives (2-PR/TMS). The cortoic acids were quantified by targeted gas chromatography–mass spectrometry (GC–MS) using a nonpolar GC column and selected ion monitoring (SIM). Baseline separation of all cortoic acids was achieved. Calibration graphs were linear (R2 > 0.98). Variations in precision and accuracy were less than 15 %, respectively. The detection limit was 100 pg (injected) with a signal-to-noise ratio of 3. 240 specimens from 24-hour urine collections from healthy children (120 boys, 120 girls, aged 3–18 years; DONALD study) were analyzed for cortoic acids and neutral cortisol metabolites to create first reference ranges. The profile of cortoic acids was dominated by α-cortolonic acid with excretion rates up to 70 µg/d. Absolute excretion rates of cortoic acids increased with age, their total excretion rates ranged between 11.0 and 127.3 µg/d (median 45.7 µg/d), but did not show any sexual dimorphism. Since cortoic acids make up only about 1 % of total urinary cortisol metabolites, determination of neutral urinary steroids reliably allows assessment of cortisol production. However, cortoic acids might present potential biomarkers of the body’s redox state.

Dietary Contributions to Metabolic Acidosis.

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production.

Selected ruminal variables and purine urinary excretion rate of steers subjected to feeding, fasting, and re-feeding conditions

The effects of feeding, fasting, and re-feeding on the ruminal profile of growing cattle were studied. Ruminal fluid and urine samples were obtained from 12 crossbred steers weighing approximately 300 kg during the following periods: 11 h of normal feeding (postprandial period), 48 consecutive hours of fasting, and followed by 48 h of re-feeding. Fasting promotes changes in the ruminal profile, such as an increase in ruminal pH, reduction in the number of rumen protozoa and bacteria, and decrease in the urinary excretion of allantoin; however, it does not change the urinary uric acid excretion rate. The overall mean ruminal pH was higher during fasting (7.53±0.27) in comparison to those at normal feeding (6.72±0.25) and re-feeding (6.62±0.31) (p⟨0.05). During re-feeding, the ruminal profile returned to normal, except for the protozoa count, which despite a slight increase only after 48 h of re-feeding, did not recover to baseline values.

NPC1L1 Deficiency Suppresses Ileal Fibroblast Growth Factor 15 Expression and Increases Bile Acid Pool Size in High-Fat-Diet-Fed Mice.

Niemann–Pick C1-like 1 (NPC1L1) mediates intestinal uptake of dietary and biliary cholesterol and is the target of ezetimibe, a cholesterol absorption inhibitor used to treat hypercholesterolemia. Genetic deletion of NPC1L1 or ezetimibe treatment protects mice from high-fat diet (HFD)-induced obesity; however, the molecular mechanisms responsible for this therapeutic benefit remain unknown. A major metabolic fate of cholesterol is its conversion to bile acids. We found that NPC1L1 knockout (L1-KO) mice fed an HFD had increased energy expenditure, bile acid pool size, and fecal bile acid excretion rates. The elevated bile acid pool in the HFD-fed L1-KO mice was enriched with tauro-β-muricholic acid. These changes in the L1-KO mice were associated with reduced ileal mRNA expression of fibroblast growth factor 15 (FGF15) and increased hepatic mRNA expression of cholesterol 7α-hydroxylase (Cyp7A1) and mitochondrial sterol 27-hydroxylase (Cyp27A1). In addition, mRNA expression of the membrane bile acid receptor Takeda G protein-coupled receptor 5 (TGR5) and type 2 iodothyronine deiodinase (Dio2) were elevated in brown adipose tissue of L1-KO mice, which is known to promote energy expenditure. Thus, altered bile acid homeostasis and signaling may play a role in protecting L1-KO mice against HFD-induced obesity.

Association Between Blood Pressure and Branched-Chain/Aromatic Amino Acid Excretion Rate in 24-Hour Urine Samples from Elderly Hypertension Patients.

BackgroundRecently, the association between lifestyle-related diseases and free amino acids in the blood plasma—especially branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs)—has been highlighted. However, few studies have been carried out on 24-hour urine samples. Therefore, we aimed to explore the relationships between 24-hour urinary BCAAs and AAAs excretion rate and blood pressure (BP) in elderly patients with hypertension.Methods and ResultsEach of the 322 elderly patients with hypertension completed an in-person questionnaire interview, underwent a physical examination, and provided a 24-hour urine specimen. We measured their BCAAs and AAAs excretion rate, and used multiple linear regression analysis with variable selection to construct models describing the relationships between their BCAAs and AAAs excretion rate and BP. After adjusted for age, gender, height, and weight, valine was inversely associated with both systolic blood pressure (SBP) (β: −0.232, 95% CI: −0.16, −0.006) and diastolic blood pressure (DBP) (β: −0.144, 95% CI: −0.089, −0.005). These findings were invariant even following adjustment for urine volume and drugs history, and Ile was positively associated with DBP (β: 0.170, 95% CI: 0.001, 0.066).ConclusionThe data revealed that the excretion rate of 24-hour urinary BCAAs was closely related to BP in elderly hypertension patients, and these findings will provide new insights into the association between BACC metabolism and BP.

High urinary excretion rate of glucose attenuates serum uric acid level in type 2 diabetes with normal renal function

Aims/IntroductionThe relationship between urinary excretion rate of glucose (UEGL) and uric acid (UA) metabolism in adults with type 2 diabetes (T2D) remains unclear to date. This study aimed to investigate the relationships of UEGL with serum UA (SUA), urinary excretion rate of uric acid (UEUA), and renal clearance of uric acid (CLUA) in adults with T2D. We hypothesised that high UEGL increases UA excretion, which in turn leads to lower SUA.Materials and methodsThis was a cross-sectional study of 635 inpatients with T2D recruited between 2018 and 2019. The relationships of UEGL with UEUA, CLUA, and hyperuricaemia were assessed using analysis of covariance and multivariate regression analysis.ResultsPatients in the higher quartile of UEGL tended to have lower SUA levels than those in the lower quartile. In contrast, patients in the higher quartile of UEGL tended to have higher CLUA (p for trend < 0.0001), and a similar trend was observed for UEUA. In adjusted multivariable linear regression model, UEGL was negatively correlated with SUA (β = − 0.023, 95% CI − 0.034 to − 0.013, p < 0.0001). However, positive correlations of UEGL with UEUA (β = 0.046, 95% CI 0.018–0.074, p = 0.001) and CLUA (β = 0.063, 95% CI 0.042–0.085, p < 0.0001) were found. Furthermore, consistent significant inverse associations were observed between quartiles of UEGL and hyperuricaemia in the adjusted multivariate logistic regression model.ConclusionsA high UEGL level was positively correlated with UEUA and CLUA. Moreover, it was inversely associated with SUA level, and a consistently increased UEGL level reduced the risk of hyperuricaemia in patients with T2D.

Changes in intestinal flora in preeclampsia rats and effects of probiotics on their inflammation and blood pressure.

The aim of this study was to investigate the changes in intestinal flora in preeclampsia rats and the effects of probiotics on their inflammation and blood pressure. A total of 40 Specific Pathogen Free (SPF) Wistar rats were randomly selected in this study. Abdominal operation was performed to reduce uterine blood perfusion, so as to establish the model of preeclampsia in rats. All rats were randomly divided into two groups, namely, observation group (treated with probiotics, n=20) and control group (not treated with probiotics, n=20). Subsequently, the changes in serum endotoxin level during intervention, the 24-h urinary 99mTc-diethylene triamine pentaacetic acid (DTPA) excretion rate, and intestinal flora colonization ability after intervention were compared between the two groups. The distribution of intestinal flora after intervention was recorded in the two groups. Meanwhile, vascular endothelial function and blood pressure following intervention were compared between the two groups as well. In addition, the changing trend of inflammatory cytokines during intervention in the two groups, and the correlation of colonization ability of intestinal flora with changes in systolic blood pressure and high-sensitivity C-reactive protein (hs-CRP) level in patients were analyzed. At 3 days and 1 week after intervention, serum endotoxin level in the observation group was significantly lower than that in the control group at the same period (p<0.05). Following intervention, observation group exhibited remarkably higher excretion rate of 24-h urinary 99mTc-DTPA (p<0.05), stronger colonization ability of intestinal flora (p<0.05), higher levels of Bifidobacteria and Lactobacillus in intestinal flora (p<0.05), lower level of endothelin-1 (ET-1) (p<0.05) and higher level of nitric oxide (NO) (p<0.05) than the control group. In addition, the systolic blood pressure and diastolic blood pressure in the observation group were basically normal, which were both notably lower than those in the control group (p<0.05). At 3 days and 1 week after intervention, the levels of serum inflammatory cytokine hs-CRP in the observation group was markedly lower than that in the control group (p<0.05) at the same period. Furthermore, the colonization ability of intestinal flora was negatively associated with the changes in systolic blood pressure and hs-CRP level in patients (p<0.05). Treating preeclampsia rats with probiotics can effectively reduce the level of serum endotoxin, improve the body's capacity to eliminate metabolites and the colonization ability of intestinal flora, maintain the stability of intestinal flora, enhance vascular endothelial function, and reduce blood pressure and the body's inflammatory responses.

Effect of Herbal Formulation “Cystone®” on Urolithiasis

Context: The study aimed to systematically review the clinical data on the efficacy of Cystone® as an herbal treatment for urolithiasis. Methods: Full text randomized clinical trials comparing Cystone® with placebo or citrate in patients with urolithiasis for urinary stone prevention or treatment were evaluated. Three databases, including PubMed, Scopus, and Cochrane Library, were searched from January 2000 to December 2017. The main outcomes were the reductions in calculi number/size and urinary excretion rate of calcium, oxalate, and urate. The secondary outcome was the adverse effects of Cystone®. Documents were screened by two reviewers for eligibility. The Jadad score was used for quality assessment. The data were analyzed using the comprehensive meta-analysis version 2.2.064 software. Results: Of 532 relevant studies, five were finally included. Cystone® was effective in the decrement of stone size in comparison with placebo (95% CI: 0.63, 9.13). There was a significant difference in the excretion rate of uric acid but not calcium compared to the placebo. Cystone® had no significant side effects. Conclusions: Cystone® is more effective than a placebo in the treatment of urinary tract stones. It significantly induces stone size decrement and clearance compared to placebo. The low quality of reports is a major limitation in the applicability of these results.

Reduced serum CTRP12 levels in type 2 diabetes are associated with renal dysfunction.

Serum C1q/TNF-related protein-12 (CTRP12) is one of the newly studied families of adipokines, which is believed to be associated with type 2 diabetes. However, the relationship between serum CTRP12 levels and diabetic nephropathy remains unclear. This study aimed to investigate the relationship between serum CTRP12 levels and renal function in patients with type 2 diabetes. A total of 115 type 2 diabetic patients and 54 healthy subjects were enrolled in this study. 52 patients with type 2 diabetes were in the diabetes group (T2DM). The 63 patients with renal dysfunction were diabetic nephropathy group (T2DM-DN) and were divided into microalbuminuria subgroup (31 cases) and macroalbuminuria subgroup (32 cases) according to the 24-h urine protein excretion rate. The concentrations of serum CTRP12 were determined by enzyme-linked immunosorbent assay. Serum CTRP12 level in T2DM and T2DM-DN groups was significantly lower compared with the control group, while CTRP12 level in T2DM-DN group was significantly lower than that in T2DM group, and was associated with the severity of renal insufficiency. After adjusting for gender and age, serum CTRP12 level was negatively correlated with the duration of diabetes, blood urea nitrogen (BUN), uric acid (UA) and 24-h urinary albumin excretion rate (UAE) in T2DM patients. Logistic regression analysis showed that serum CTRP12 level was significantly associated with renal dysfunction in type 2 diabetes mellitus. And the duration of diabetes, total cholesterol (CHOL) and neutrophils/lymphocytes (NLR) are independent risk factors for renal dysfunction in type 2 diabetes mellitus. Serum CTRP12 may be involved in the occurrence and development of diabetic nephropathy. Trial registration number and date of registration ChiCTR2000030794, March 14, 2020.

Association of Dietary Acid Load with the Prevalence of Metabolic Syndrome among Participants in Baseline Survey of the Japan Multi-Institutional Collaborative Cohort Study

The association between dietary acid load and metabolic syndrome (MetS) has not been fully investigated. A cross-sectional study was performed on 14,042 men and 14,105 women (aged 35–69 years) who participated in a baseline survey of the Japan Multi-Institutional Collaborative Cohort study. Dietary acid load was assessed using the net-endogenous-acid-production (NEAP) score that is closely correlated with the rate of renal net acid excretion. MetS was diagnosed according to the Joint Interim Statement Criteria of 2009 using body-mass index instead of waist circumference. After adjusting for potential confounders, higher NEAP scores were associated with a significantly increased odds ratio (OR) of MetS, obesity, high blood pressure, and high fasting blood glucose. These associations remained significant after further adjustment for carbohydrate intake or two nutrient-pattern scores significantly associated with MetS. After adjustment for fiber, iron, potassium, and vitamin pattern scores, the OR of MetS for the highest quartile of NEAP scores, relative to the lowest quartile, was 1.25 (95% confidence interval 1.12–1.39). There was no significant interaction between sex, age, or body-mass index and NEAP. Higher dietary acid load was associated with a higher prevalence of MetS and several of its components, independently of carbohydrate intake or nutrient patterns.

SCREENING AND ASSESSMENT OF CARDIAC AUTONOMIC NEUROPATHY IN LONG STANDING TYPE 2 DIABETIC WOMEN

Patients with long-standing diabetes mellitus undergoing surgical interventions are under considerable risk, hence posing a surgical challenge, as they may have cardiovascular and/or cardiac autonomic neuropathy (CAN). CAN is serious, often overlooked and underdiagnosed, with possible arrhythmias and silent ischemia that may be life threatening. The aim of this study was to screen for one of the underdiagnosed high-risk problems by assessment of CAN in long-standing type 2 diabetic women undergoing stressful situations. Cross-sectional study. Hundred type 2 diabetic women scheduled for major surgery were assessed by autonomic function tests. CAN was assessed by analyzing heart rate variations during three standard tests (deep breathing, lying to standing, and the valsalva maneuver). Sympathetic functions were assessed by checking orthostatic hypotension. The CAN score of each patient was analyzed. Continuous 24 h ECG monitoring was performed to evaluate arrhythmia, corrected QT (QTc), and QT dispersion (QTd). Transthoracic Doppler echocardiography, with a focus on left ventricular hypertrophy, diastolic, and systolic dysfunctions, was carried out. Patients were classified as having mild (with only one abnormal test) or severe CAN when two or more abnormal function tests were present. Exclusion criteria included any systemic illness that could affect the results of the study or the autonomic functions, smoking, hypertension, and patients with evident ischemia. CAN was detected in 70% of the patients studied, and 70% of them had a severe case of CAN. Postural hypotension was detected in 34% of the patients studied. QTc prolongation and QTd were frequent. ECG and Doppler echocardiography changes of left ventricular hypertrophy were more prevalent among patients with CAN. Diabetics with CAN were significantly older, had a longer duration of diabetes mellitus, and higher HbA1-c, higher pulse pressure, triglyceride, uric acid, and urinary albumin excretion rate. They also had a significantly increased left ventricular mass index and diastolic dysfunction. Middle-aged women with long-standing diabetes are vulnerable to CAN with postural hypotension and prolonged QTc intervals, QTd, and increased left ventricular mass index. Identification of CAN is crucial to prevent the hazards of cardiovascular insults during stressful situations, and cases with severe CAN may require coronary artery disease screening preoperatively.

Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis

Disruption of hepatic small heterodimer partner induces dissociation of steatosis and inflammation in experimental nonalcoholic steatohepatitis

Urinary excretion rate and bioavailability of chlorogenic acid, caffeic acid, p-coumaric acid, and ferulic acid in non-fasted rats maintained under physiological conditions

Hydroxycinnamic acids (HAs) are one of the major classes of phenolic compounds and epidemiological studies have suggested that they have beneficial health effects. This study aimed to determine the urinary excretion rate of chlorogenic acid, caffeic acid, p-coumaric acid, and ferulic acid in non-fasted rats and to estimate their bioavailability under physiological conditions. Previous studies have primarily used fasted animals, which exhibit severe changes in various physiological processes. Furthermore, the food matrix can affect HA bioavailability. Thus, our studies using non-fasted rats under physiological conditions may allow for a more accurate determination of both the HA urinary excretion rate and the bioavailability of HAs. HAs were successively gavaged to rats at a dose of 40 mg/kg body weight (BW) with a wash-out period of one week. The rats were fed the AIN-93M diet throughout the experiment. The urine was collected at time intervals of 0–6 h, 6–24 h, and 24–48 h after HA administration. Ingested HAs, except chlorogenic acid, were primarily excreted in the urine within 0–6 h as free forms or conjugated (glucuronidated and/or sulfated) forms. The majority of the ingested chlorogenic acid was detected in the urine at 6–24 h or 24–48 h as caffeic acid, p-coumaric acid, ferulic acid, and their conjugates. The total urinary excretion rate (% of the dose) at 48 h was ferulic acid (73.2%) > caffeic acid (61.6%) >p-coumaric acid (54.1%) >> chlorogenic acid (4.9%). The percentages of the conjugates in the urine differed amongst the rats gavaged with the individual HAs (74% for chlorogenic acid, 83% for caffeic acid, 68% for p-coumaric acid, and 96% for ferulic acid), which may be explained by their distinct bioactivities. These data reveal that caffeic acid, p-coumaric acid, and ferulic acid are much more bioavailable than chlorogenic acid, even though they are excreted more rapidly than chlorogenic acid. Our findings may provide additional insight into the health benefits of HAs and how they function in the body.