Mean Excretion Research Articles

Sodium and potassium excretion and its association with cardiovascular disorders in Mexican adults.

Worldwide, as well as in Mexico, the leading cause of death is cardiovascular disease (CVD). Hypertension is the main risk factor for CVD; about 50% of the adult population suffers from this condition. High sodium (Na) intake combined with low potassium (K) intake can trigger cardiovascular disorders such as high blood pressure (BP). The aim of this study was to estimate the mean excretion of Na and K in Mexican adults using a spot urine sample, and its association with cardiovascular disorders. Information on 2,778 adults, 20-59 years of age, who participated in ENSANUT-2016 was analyzed. Na and K were estimated using Tanaka formulae. Biomarkers such as glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol, and anthropometry were measured. Mean Na was 3,354 mg/day (95%CI: 3,278, 3,429), 1,440 mg/day of K (95%CI: 1,412, 1,469), and the Na-K ratio was 2.4. The excretion of Na was greater in adults with high BP (3,542 mg/day) compared to those with normal BP (3,296 mg/day). In adults with hypertension, excretion of K was 10% greater (1,534 mg/day) than in adults with normal BP (1,357 mg/day). In adults with moderate reduction of renal function, Na excretion was 22% less (2,772 mg/day) than in adults with normal kidney function (3,382 mg/day). The results of this study show that the cardiovascular health of Mexican adults is at risk, as they showed high Na excretion and low K excretion.

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program

BackgroundMucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of β-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII.MethodsThis disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022.ResultsAs of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and − 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died.ConclusionsTo date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

Estimation of 24-hour urinary sodium and potassium excretion among Chinese adults: a cross-sectional study from the China National Nutrition Survey

BackgroundHigh-sodium intake is one of the most important risk factors for hypertension and cardiovascular disease, yet reliable national estimates of sodium intake in Chinese adults have not been reported. ObjectivesWe estimated 24-h urinary sodium and potassium excretion and population daily sodium and potassium intake of Chinese adults for the first time at a national level. MethodsA nationally representative cross-sectional survey was conducted to collect 24-h urine specimens from Chinese adults aged ≥18 y as part of the China National Nutrition Survey 2015. Finally, 10,114 participants (4932 males and 5182 females) with complete 24-h urine specimens were included in the analysis. Estimates of mean urinary electrolyte excretion and demographic, socioeconomic, and health characteristics were used with weighted coefficients that accounted for sample selection probabilities, poststratification weighting, and nonresponse rates. ResultsThe estimation of overall weighted mean 24-h urinary sodium excretion was 4121 mg (95% confidence interval [CI]: 3993, 4250), 4155 mg (95% CI: 3993, 4317) in males and 4081 mg (95% CI: 3953, 4209) in females (P for sex difference = 0.36). Overall mean 24-h urinary potassium excretion was 1534 mg (95% CI: 1492, 1577), 1468 mg (95% CI: 1424, 1513) in males and 1614 mg (95% CI: 1569–1660) in females (P for sex difference <0.001). Mean 24-h urinary sodium excretion was significantly higher in rural adults (4350 mg; 95% CI: 4217, 4483) than in urban residents (3909 mg; 95% CI: 3739, 4080; P < 0.001), and in northern residents (4388 mg; 95% CI: 4237, 4539) than in southern residents (3998 mg; 95% CI: 3832, 4163; P = 0.002). ConclusionsThe first nationwide survey with 24-h urine collection confirmed that mean sodium intake in Chinese adults was more than twice the upper limit, whereas mean potassium intake was <60% of the lower limit, recommended by the World Health Organization. Urgent measures should be taken to reduce sodium intake and increase potassium intake in China.

Empirical measurements of ammonium excretion in kelp forest fishes: Effects of body size, taxonomy and trophic guild

Fishes and other consumers excrete metabolic waste products, including dissolved nutrients rich in nitrogen, which is an essential nutrient for primary production. Relatively little is known about the magnitude and variability of nutrients excreted by fishes in kelp forest ecosystems and whether consumer-derived nutrients are important for supporting kelp productivity. In this study, the supply of ammonium (NH4+) excreted by the dominant fishes (30 species representing ∼85% of total fish biomass) was investigated on nearshore rocky reefs in California. Using rapid field incubations, the amount of excreted dissolved ammonium was measured as a function of body size (n = 460 individuals) and predictive models were developed relating mass to excretion rates at the family-level. Mass-specific excretion rates ranged from 0.08 to 3.45 μmol·g−1·hr−1, and per capita ammonium excretion rates ranged from 5.9 to 2765 μmol·individual·hr−1. Ammonium excretion scaled with fish body mass to the ¾ power, as predicted by the metabolic theory of ecology; mass-specific excretion rates were higher in smaller fishes, but larger fishes contributed more ammonium per individual. When controlling for body size, ammonium excretion rates were greatest among surfperch (Embiotocidae), damselfish (Pomacentridae), and wrasses (Labridae), and the general trophic groups of planktivores and micro-carnivores. When body size differences were considered, the greatest mean excretion rates per individual were observed in larger-bodied species, such as California Sheephead (Semicossyphus pulcher) and Lingcod (Ophiodon elongatus). Empirical estimates of nutrient excretion by fishes, among the first measured in temperate kelp forests, were consistent with those in other aquatic systems. Ultimately, empirically derived excretion rates are the first step to quantifying the relative importance of consumers to nutrient cycling in kelp forest ecosystems.

Productivity parameters, antimicrobial consumption, and prevalence of enteric pathogens before and after intramuscular vaccination against Lawsonia intracellularis in naturally infected Danish weaner and finisher pig herds.

In Danish pig production, gastro-intestinal diseases account for most of the antimicrobials (AM) used in growing pigs. Diarrhoea is most frequently caused by Lawsonia intracellularis (LI), Brachyspira pilosicoli (BP), E coli fimbria type F4 (F4) and E. coli fimbria type F18 (F18). With a new LI vaccine available from 2019, it was relevant to investigate the effect of this vaccine in a Danish field study including both weaner and finisher sites. The aim was to evaluate the efficacy of Porcilis® Lawsonia Vet. in naturally LI-infected pig herds by comparing of productivity parameters, AM consumption and dynamics of enteric pathogens over two 6-months periods before and after LI vaccination. Further, faecal sock samples were collected from each site before and after vaccination and analysed by qPCR for excretion levels of LI, BP, F18 and F4. In total, 28 weaner and 41 finisher sites were included in the study. Vaccination reduced Feed Conversion Ratio by 0.12 Feed Unit/kg (p=0.029) and 0.08 Feed Unit/kg (p=0.005) in weaners and finishers, respectively. Increased Average Daily Weight Gain of 45.6 gr./day (p< 0.001) was found in the finishers. Mortality risk fell by 8.8% in weaners (RR = 0.912; p< 0.001). AM prescriptions for oral group treatments were reduced by 38.8% active compound/kg pig produced (p=0.005) or 33.3% Weighted Animal Daily Doses per 100 animals per day in finishers (p=0.004). LI prevalence was reduced in weaners and finishers (both p <0.001) and BP prevalence was reduced in finishers (p=0.043). Mean excretion levels of LI and BP decreased at weaner sites (-1.32 and -1.02log(10) copies/gr faeces, respectively; both p< 0.001) and at finisher sites (-1.04 and -1.16log(10) copies/gr faeces, respectively; both p< 0.001). Prevalence and excretion levels of F18 and F4 were unaffected by LI vaccination. In conclusion, vaccination against LI using Porcilis® Lawsonia Vet. improved productivity parameters, cut AM consumption, and reduced prevalence and excretion levels of LI and BP in naturally LI-infected pig herds.

#2971 LONG-TERM EFFECTS OF THE NEW NORDIC RENAL DIET ON PHOSPHOROUS HOMEOSTASIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4

Abstract Background and Aims Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2]. Method A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23). Results Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P &amp;lt; 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria. Conclusion NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.

Evidence Linking Cadmium Exposure and β2-Microglobulin to Increased Risk of Hypertension in Diabetes Type 2.

The most common causes of chronic kidney disease, diabetes, and hypertension are significant public health issues worldwide. Exposure to the heavy metal pollutant, cadmium (Cd), which is particularly damaging to the kidney, has been associated with both risk factors. Increased levels of urinary β2-microglobulin (β2M) have been used to signify Cd-induced kidney damage and circulating levels have been linked to blood pressure control. In this study we investigated the pressor effects of Cd and β2M in 88 diabetics and 88 non-diabetic controls, matched by age, gender and locality. The overall mean serum β2M was 5.98 mg/L, while mean blood Cd and Cd excretion normalized to creatinine clearance (Ccr) as ECd/Ccr were 0.59 µg/L and 0.0084 µg/L of filtrate (0.95 µg/g creatinine), respectively. The prevalence odds ratio for hypertension rose by 79% per every ten-fold increase in blood Cd concentration. In all subjects, systolic blood pressure (SBP) showed positive associations with age (β = 0.247), serum β2M (β = 0.230), and ECd/Ccr (β = 0.167). In subgroup analysis, SBP showed a strong positive association with ECd/Ccr (β = 0.303) only in the diabetic group. The covariate-adjusted mean SBP in the diabetics of the highest ECd/Ccr tertile was 13.8 mmHg higher, compared to the lowest tertile (p = 0.027). An increase in SBP associated with Cd exposure was insignificant in non-diabetics. Thus, for the first time, we have demonstrated an independent effect of Cd and β2M on blood pressure, thereby implicating both Cd exposure and β2M in the development of hypertension, especially in diabetics.

24-hour sodium and potassium excretion in the Americas: a systematic review and meta-analysis.

To determine the 24-hour urinary sodium and potassium excretions in the Americas. A systematic review and meta-analysis were performed seeking for studies conducted between 1990 and 2021 in adults living in any sovereign state of the Americas in Medline, Embase, Scopus, SciELO, and Lilacs. The search was first run on October 26th, 2020 and was updated on December 15th, 2021. Of 3 941 abstracts reviewed, 74 studies were included from 14 countries, 72 studies reporting urinary sodium (27 387 adults), and 42 studies reporting urinary potassium (19 610 adults) carried out between 1990 and 2020. Data were pooled using a random-effects meta-analysis model. Mean excretion was 157.29 mmol/24h (95% CI, 151.42-163.16) for sodium and 57.69 mmol/24h (95% CI, 53.35-62.03) for potassium. When only women were considered, mean excretion was 135.81 mmol/24h (95% CI, 130.37-141.25) for sodium and 51.73 mmol/24h (95% CI, 48.77-54.70) for potassium. In men, mean excretion was 169.39 mmol/24h (95% CI, 162.14-176.64) for sodium and 62.67 mmol/24h (95% CI, 55.41-69.93) for potassium. Mean sodium excretion was 150.09 mmol/24h (95% CI, 137.87-162.30) in the 1990s and 159.79 mmol/24h (95% CI, 151.63-167.95) in the 2010s. Mean potassium excretion was 58.64 mmol/24h (95% CI, 52.73-64.55) in the 1990s and 56.33 mmol/24/h (95% CI, 48.65-64.00) in the 2010s. These findings suggest that sodium excretions are almost double the maximum level recommended by the World Health Organization and potassium excretions are 35% lower than the minimum requirement; therefore, major efforts to reduce sodium and to increase potassium intakes should be implemented.

Derivatives of 2-Methyl Tetrahydrofuran-n-Carboxylic Acids Inhibiting Novel HA3 Subtype of Influenza A Virus Hemagglutinin

The HA3 influenza (H3N2) influenza was originally found in 2011 and later appeared in January 2021. As per WHO report, H3N2 has the potential of causing a pandemic; therefore, an inhibitor for H3N2 should be designed. The hemagglutinin variants have typical 18 subtypes present in humans. Therefore, in the study, we generated the phylogenetic tree for understanding the similarity sequence between 18 subtypes and also the sequence of similarity was compared to H3N2. Thereafter, scaffold structures of FDA-approved Peramivir were generated, among which, four compounds were selected based on their drug-likeness and synthetic feasibility for performing docking and MD simulations. Theoretical evaluations, such as electronic, spectroscopic, binding energy, Root Mean Square Deviation (RMSD), Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET), were performed to validate the derived chemical structures and identify their potential of acting as drug compounds. In the present work, derivatives of 2-methyl tetrahydrofuran-[Formula: see text]-carboxylic acids show the inhibitory activity with H3N2 (PDB ID: 4WEA) with stable conformations.

MO435: The Prognostic Implication of 24-h Urine Urea Excretion With Renal Progression: Analysis of KNOW-CKD Study

Abstract BACKGROUND AND AIMS Urea excretion is the basic function of the nephron. However, its prognostic implication has been not extensively studied in a specific subpopulation of chronic kidney diseases (CKD). METHOD Total of 2232 patients in KNOW-CKD cohort were analyzed. Baseline characteristics were used as a prognosticator in the Cox regression model. For categorical comparison, tertiles of 24-h urea excretion were used as high, low and moderate excretion of urea. Linear modelling and nonlinear modelling based on restricted cubic splines were used to study the impact of 24-h urea excretion on renal survival. RESULTS Mean daily urea excretion was 8.2 ± 3.6 g/day. Mean daily urea excretion was 12.1 ± 3.1 g/day versus 4.8 ± 1.3 g/day in the high urea excretion group (HUG) and low urea excretion group (LUG) (P &amp;lt; 0.001). Mean eGFR of LUG was 47.0 ± 30.9 mL/min/1.73m2 and mean eGFR of HUG was 60.6 ± 29.9 mL/min/1.73m2 (P &amp;lt; 0.001). Serum albumin level was higher in HUG with 4.3 ± 0.4 g/dL versus 4.1 ± 0.5 g/dL of LUG (P &amp;lt; 0.001). Compared with HUG, LUG showed a hazard ratio of end-stage renal disease (ESRD) with 1.407 [95% confidence interval (CI) 1.115–1.774, P = 0.004] in the linear multiple regression model, which was adjusted by eGFR, age, gender, body mass index, type of CKD, proteinuria amount, systolic blood pressure, hemoglobin, blood urea nitrogen, serum albumin, serum cholesterol, serum uric acid, hsCRP, statin usage, renin-angiotensin-aldosterone system blocker usage. In the non-linear modeling, daily urea excretion showed a two-step change in log hazard ratio to ESRD. Threshold points of log hazard ratio among the whole study population were observed at 5 g/day and 15 g/day, respectively. The reduction of log hazard ratio in the HUG was more clear in the eGFR 30–60 mL/min/1.73m2 subpopulation (Figure 1C). Similarly, a reduction in log hazard ratio in the HUG was observed in glomerulonephritis, polycystic kidney disease subpopulations, but not in the diabetes mellitus nephropathy subpopulation (Figure 1D–F). CONCLUSION Daily urea urine excretion showed prognostic implications in the CKD stage 3 subgroups, glomerulonephritis subgroups and polycystic kidney disease subgroups. In the following researches, studies focusing on interventional targets in the context of daily urea excretion in those subgroups should be warranted.

The role of caloric intake in the association of high salt intake with high blood pressure

Since current recommendations call for a substantial reduction in overall sodium consumption, we tested whether or not these recommendations are implemented in common large subpopulations such as those with abnormal weight or hypertension in the current high sodium, high-calorie nutritional environment. In a national representative cross-sectional survey of the community-dwelling subjects aged 25–65 years conducted in Israel between 2015 and 2017, 582 randomly selected subjects completed health and dietary questionnaires, underwent blood pressure and anthropometric measurements and collected 24-h urine specimens, to assess dietary sodium intake. Overall mean 24-h sodium excretion was 3834 mg, more than double the recommended upper intake for adults < 1500 mg/day. Sodium excretion was directly related to caloric intake and blood pressure and linked to the presence of hypertension and overweight/obesity. The highest sodium excretion was seen in overweight/obese hypertensive subjects. This recent national survey shows a high consumption of sodium in the Israeli population and a dose–response association between caloric intake and urinary sodium excretion, independent of BMI and hypertension. Nevertheless, overweight/obese subjects with hypertension consume (excrete) more sodium than other BMI/ blood pressure-related phenotypes and may thus comprise a target subpopulation for future efforts to reduce sodium intake.

Evaluation of the potential of total proanthocyanidin content in feces as an intake biomarker

Due to the health benefits associated with proanthocyanidins (PAs), it is useful to identify dietary PA biomarkers that can be determined by simple methods. Since increased levels of circulating PA metabolites are associated with increased fecal PA content, this study explores the spectrophotometric measurement of fecal PA content and its use as a biomarker of PA intake. To this end, fecal PA content was measured using an adaptation of Porter’s spectrophotometric method in samples from a preclinical study and an observational study. In the former, excretion of 250–400 mg PA polymer equivalents/100 g feces was observed during supplementation and the day after, together with a significant association (p < 0.05) between PA intake and the excretion of both intact PAs and some PA metabolites, i.e., (+)-catechin, (−)-epicatechin and syringic acid. No relationship between intake and excretion was found in the observational study, either for the entire group (mean excretion of 240 ± 226 mg PA polymer equivalents/100 g feces) or after stratification into tertiles of consumption. In conclusion, the spectrophotometric determination of total PA content in feces proved to be a valid compliance marker in a preclinical study, but it was not associated with PA intake in free-living subjects. The potential of total PA excretion in observational studies, determined in fecal samples collected the day before dietary recall or in several fecal samples from the same subject, remains to be elucidated, as does a complete validation of the method proposed here.

Determination of the route of excretion of robenacoxib (Onsior™) in cats and dogs: A pilot study.

The objective of the studies was to determine the route of excretion, faecal or urinary, of the nonsteroidal anti-inflammatory drug (NSAID) robenacoxib (Onsior™) in cats and dogs. The studies employed a two-part crossover design in 4 beagle dogs (2 female and 2 male, age 36-41months and body weight 9.0-10.3kg) and a parallel group comparison of two groups each of 3 domestic short-hair cats (2 female and 4 castrated male, age 35-73months and body weight 3.0-5.7kg). Animals were administered single doses of 1 (dog) or 2 (cat) mg/kg of [14 C]-robenacoxib by intravenous (IV) and oral routes. Venous blood samples were taken and analysed for robenacoxib concentration. Faeces and urine were collected for 4 (cats) or 7 (dogs) days and analysed for radioactivity. Robenacoxib was eliminated rapidly from blood (≤ 8hr). In dogs, expressed as the percentage of the administered dose and adjusted so that faecal plus urine recovery was 100%, the mean (SD) excretion in faeces and urine was, respectively, 64.6% (4.30) and 35.4% (4.3) after IV and 66.7% (6.9) and 33.3% (6.9) after oral administration. The respective values in cats, in faeces and urine, were 72.5% (4.6) and 27.5% (4.6) after IV and 78.5% (2.6) and 21.5% (2.6) after oral administration. In conclusion, excretion of systemically available robenacoxib in cats and dogs was mixed via both faeces and urine, but predominately faecal (~64.6% in dogs and ~72.5% in cats) and assumed to be via biliary excretion.

UP-REGULATION OF SGLT-5 AS A CAUSE OF FRUCTOSE-INDUCED VOLUME-DEPENDENT HYPERTENSION

Objective: Excessive intake of fructose causes a variety of adverse conditions including obesity, hepatic steatosis, insulin resistance, uric acid overproduction and hypertension which is the most common and significant pathological setting. Cause of the hypertension is not known at present. This study aimed to elucidate the underlying mechanism of fructose-induced hypertension by rat model. Design and method: Male SD rats (7 weeks old) were fed by food containing 60% glucose (GLU) and 60% fructose (FRU) for 3, 6 and 12 weeks. Histological, immunohistological and molecular biological analysis, and gene chip study were applied. No difference of calorie and salt intake of individual animal was daily checked by the measured weight of remaining food. Results: Mean blood pressure and fractional sodium excretion (FENa) of FRU were both significantly higher (BP 12w-GLU: 94.8 ± 3.4 vs 12w-FRU: 103.7 ± 1.2 mmHg; FENa 12w-GLU: 0.084 ± 0.011 vs 12w-FRU: 0.059 ± 0.08%), suggesting that fructose caused ECF volume-dependent hypertension. Glomerular expansion in FRU (glomerular surface area in 12w-GLU: 7495 ± 181 vs 12w-FRU: 9831 ± 164 square micrometer) was agreed with the increase in the ECF volume. The expression of GLUT-5, fructose entry pathway, and ketohexokinase, phosphatase of fructose, in the proximal tubule were both up-regulated by fructose. As a candidate of fructose-induced salt reabsorption pathway, NHE3 was focused first because it is principal salt reabsorption pathway of proximal tubule. However, gene expression analysis, immunohistochemistry and immunoblotting of whole and phosphorylated NHE3 indicated negative results. To explore salt transporting molecules responding to fructose, gene chip analysis was conducted, and Slc5a10, corresponding to SGLT-5, showed significant up-regulation. The result was confirmed by RT-PCR (12w-GLU: 75.0 ± 5.8% vs 12w-FLU: 230.1 ± 16.0%) and in-situ hybrydization. Conclusions: Excess intake of fructose caused volume-dependent hypertension due to increased salt reabsorption through fructose-induced up-regulation of SGLT-5.

Unbalanced intakes of sodium and potassium among Tunisian adults: A cross-sectional study.

The prevention and management of hypertension are untimely associated with a lowering of sodium intake. The present study aimed to evaluate the sodium and potassium intake levels of Tunisian population through measurement of 24‐hr urinary sodium excretions. A randomly, multistage, cross‐sectional study was conducted in an urban region (Bizerte) in Tunisia during 2015. The target population involved adults aged from 25 to 64 years. Sodium, potassium, and creatinine concentrations were determined in each urine sample using indirect potentiometric method. From the 420 selected participants, only 194 gave urine samples complying completeness criteria. A multivariate regression model was used to assess the variables related to sodium and potassium excretion. The daily mean excretion of sodium and potassium was 138.3 ± 46.5 mmol/d (corresponding to 8.1 ± 2.7 g/d of salt intake) and 61.0 ± 22.7 mmol/d, respectively. More than 87.1% of the participants (89.8% for men vs. 84.9% for women; p = .31) exceeded the WHO recommendation of 5 g/d. The upper limit of 10 g salt intake per day was still exceeded by 26.3%. After adjusted analysis, sex (for women, coef = −1.6; (95% CI: −2.4, −0.7)), level of instruction (≥30 kg/m2, coef = +1.1; (95% IC: 0.4–2.0)), and body mass index (≥30 kg/m2, coef = +1.1; (95% CI: 0.1, 2.0)) were associated with the sodium excretion. High sodium intake and inadequate potassium intake were found among participants. This consumption profile complies with the diet westernization context occurring in Tunisia. The initiated strategy focused on the downward of sodium in bread (the main source of salt intake) seems to be promising.

Reduction of oxidative stress on DNA and RNA in obese patients after Roux-en-Y gastric bypass surgery-An observational cohort study of changes in urinary markers.

Increased oxidative stress in obesity and diabetes is associated with morbidity and mortality risks. Levels of oxidative damage to DNA and RNA can be estimated through measurement of 8-oxo-7,8-dihydro-2´-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) in urine. Both markers have been associated with type 2 diabetes, where especially 8-oxoGuo is prognostic for mortality risk. We hypothesized that Roux-en-Y gastric bypass (RYGB) surgery that has considerable effects on bodyweight, hyperglycemia and mortality, might be working through mechanisms that reduce oxidative stress, thereby reducing levels of the urinary markers. We used liquid chromatography coupled with tandem mass spectrometry to analyze the content of 8-oxodG and 8-oxoGuo in urinary samples from 356 obese patients treated with the RYGB-procedure. Mean age (SD) was 44.2 (9.6) years, BMI was 42.1 (5.6) kg/m2. Ninety-six (27%) of the patients had type 2 diabetes. Excretion levels of each marker before and after surgery were compared as estimates of the total 24-hour excretion, using a model based on glomerular filtration rate (calculated from cystatin C, age, height and weight), plasma- and urinary creatinine. The excretion of 8-oxodG increased in the first months after RYGB. For 8-oxoGuo, a gradual decrease was seen. Two years after RYGB and a mean weight loss of 35 kg, decreased hyperglycemia and insulin resistance, excretion levels of both markers were reduced by approximately 12% (P < 0.001). For both markers, mean excretion levels were about 30% lower in the female subgroup (P < 0.0001). Also, in this subgroup, excretion of 8-oxodG was significantly lower in patients with than without diabetes. We conclude, that oxidative damage to nucleic acids, reflected in the excretion of 8-oxodG and 8-oxoGuo, had decreased significantly two years after RYGB-indicating that reduced oxidative stress could be contributing to the many long-term benefits of RYGB-surgery in obesity and type 2 diabetes.

Gut passage time and viability of seeds consumed by Australian marsupials

Many Australian mammals consume seeds, but their role in seed dispersal has not been well explored. Here, we investigated the mean retention time and the postconsumption germination capacity of Australian seeds (Acacia acuminata, Dodonaea viscosa and Gastrolobium calycinum) likely to be consumed by quenda (Isoodon fusciventer) and woylies (Bettongia penicillata ogilbyi). Mean excretion times were 14h for quenda and 24h for woylies, but some seeds were retained in their digestive passages for up to 39.5 and 55.5h, respectively. Viable seeds of all plant species were retrieved from both species’ scats and only G. calycinum seeds ingested by quenda had a significantly higher germination percentage (62%) than control seeds (34%). Our results show that viable seeds are deposited in the scats of quenda and woylies, indicating that these species may play a role in seed dispersal.

MTXPK.org: A Clinical Decision Support Tool Evaluating High-Dose Methotrexate Pharmacokinetics to Inform Post-Infusion Care and Use of Glucarpidase.

Methotrexate (MTX), an antifolate, is administered at high doses to treat malignancies in children and adults. However, there is considerable interpatient variability in clearance of high‐dose (HD) MTX. Patients with delayed clearance are at an increased risk for severe nephrotoxicity and life‐threatening systemic MTX exposure. Glucarpidase is a rescue agent for severe MTX toxicity that reduces plasma MTX levels via hydrolysis of MTX into inactive metabolites, but is only indicated when MTX concentrations are > 2 SDs above the mean excretion curve specific for the given dose together with a significant creatinine increase (> 50%). Appropriate administration of glucarpidase is challenging due to the ambiguity in the labeled indication. A recent consensus guideline was published with an algorithm to provide clarity in when to administer glucarpidase, yet clinical interpretation of laboratory results that do not directly correspond to the algorithm prove to be a limitation of its use. The goal of our study was to develop a clinical decision support tool to optimize the administration of glucarpidase for patients receiving HD MTX. Here, we describe the development of a novel 3‐compartment MTX population pharmacokinetic (PK) model using 31,672 MTX plasma concentrations from 772 pediatric patients receiving HD MTX for the treatment of acute lymphoblastic leukemia and its integration into the online clinical decision support tool, MTXPK.org. This web‐based tool has the functionality to utilize individualized demographics, serum creatinine, and real‐time drug concentrations to predict the elimination profile and facilitate model‐informed administration of glucarpidase.

Maternal Glucocorticoid Metabolism Across Pregnancy: A Potential Mechanism Underlying Fetal Glucocorticoid Exposure

Across pregnancy, maternal serum cortisol levels increase up to 3-fold. It is not known whether maternal peripheral cortisol metabolism and clearance change across pregnancy or influence fetal cortisol exposure and development. The primary study objective was to compare maternal urinary glucocorticoid metabolites, as markers of cortisol metabolism and clearance, between the second and third trimester of pregnancy. Secondary objectives were to test associations of total maternal urinary glucocorticoid excretion, with maternal serum cortisol levels and offspring birth weight z score. A total of 151 women with singleton pregnancies, recruited from prenatal clinic at the Pittsburgh site of the Measurement of Maternal Stress (MOMS) study, had 24-hour urine collections during both the second and third trimesters. Between the second and third trimester, total urinary glucocorticoid excretion increased (ratio of geometric means [RGM] 1.37, 95% CI 1.22-1.52, P < .001), and there was an increase in calculated 5β-reductase compared to 5α-reductase activity (RGM 3.41, 95% CI 3.04-3.83, P < .001). During the third trimester total urinary glucocorticoid excretion and serum cortisol were negatively correlated (r = -0.179, P = .029). Mean total urinary glucocorticoid excretion across both trimesters and offspring birth weight z score were positively associated (β = 0.314, P = .001). The estimated activity of maternal enzymes responsible for cortisol metabolism change between the second and third trimester of pregnancy. Additionally, maternal peripheral metabolism and clearance of cortisol may serve as a novel mechanism affecting fetal cortisol exposure and growth.

Pharmacokinetics of Bismuth following Oral Administration of Wei Bi Mei in Healthy Chinese Volunteers.

Background Bismuth-containing quadruple therapy achieves higher eradication rate of Helicobacter pylori. High level of bismuth in blood may result in damage of many organs. Wei Bi Mei is a new bismuth-containing drug combining chemicals and Chinese medicine portions. The present research is to study the pharmacokinetics of bismuth to evaluate the safety and rational use of Wei Bi Mei granules. Material and Methods. Seven healthy Chinese adult subjects were enrolled in this research, which included a single-dose study and a multiple-dose study. Wei Bi Mei granules were administered orally to the subjects at corresponding time. Blood and urine were collected. All samples were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Results For single-dose Wei Bi Mei granules administration, the mean time to peak concentration (tmax) of bismuth was 2.29 ± 0.76 h, and the mean peak concentration (Cmax) of bismuth was 0.85 ± 0.55 ng/mL. For multiple-dose Wei Bi Mei granules administration, the Cmax was 2.25 ± 1.18 ng/mL at day two, and the volume of distribution (Vd) was (22.97 ± 9.82) × 103 L. The urinary excretion of bismuth was the fastest during the first two days, with a mean excretion rate of 3.84 ± 1.23 ng/h. The bismuth concentration in urine was significantly reduced at day 16. Conclusion Bismuth has a washout period of approximately two months. The concentration of bismuth in blood was far less than the “safe level.” Thus, Wei Bi Mei is a highly safe therapeutic medicine, with a good clinical application value. Wei Bi Mei should be recommended more widely for use in bismuth-containing quadruple therapy for the treatment of Helicobacter pylori infection.