Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study.

BACKGROUND: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. OBJECTIVE: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. METHODS: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. RESULTS: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. CONCLUSIONS: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Complementary Regulation of BfmRS Two-Component and AbaIR Quorum Sensing Systems to Express Virulence-Associated Genes in Acinetobacter baumannii.

Acinetobacter baumannii expresses various virulence factors to adapt to hostile environments and infect susceptible hosts. This study investigated the regulatory network of the BfmRS two-component and AbaIR quorum sensing (QS) systems in the expression of virulence-associated genes in A. baumannii ATCC 17978. The ΔbfmS mutant exhibited a significant decrease in surface motility, which presumably resulted from the low expression of pilT and A1S_0112-A1S_0119 gene cluster. The ΔbfmR mutant displayed a significant reduction in biofilm and pellicle formation due to the low expression of csu operon. The deletion of abaR did not affect the expression of bfmR or bfmS. However, the expression of abaR and abaI was upregulated in the ΔbfmR mutant. The ΔbfmR mutant also produced more autoinducers than did the wild-type strain, suggesting that BfmR negatively regulates the AbaIR QS system. The ΔbfmS mutant exhibited no autoinducer production in the bioassay system. The expression of the A1S_0112-A1S_0119 gene cluster was downregulated in the ΔabaR mutant, whereas the expression of csu operon was upregulated in this mutant with a high cell density. In conclusion, for the first time, we demonstrated that the BfmRS-AbaIR QS system axis regulated the expression of virulence-associated genes in A. baumannii. This study provides new insights into the complex network system involved in the regulation of virulence-associated genes underlying the pathogenicity of A. baumannii.

Complete Genome Resource of Serratia plymuthica C-1 that Causes Root Rot Disease in Korean Ginseng.

Serratia plymuthica C-1, a biocontrol agent, was isolated from soil collected from a mountain forest in Korea. Previous studies have shown that certain strains of S. plymuthica cause root rot disease in ginseng. To the best of our knowledge, this is the first report of the sequence of the circular chromosome of S. plymuthica C-1, which plays a dual role by causing root rot in ginseng and exhibiting biocontrol activity. The findings of this study will assist in analyzing the genes associated with the pathogenicity and biocontrol properties of S. plymuthica.

Mussel adhesion-employed water-immiscible fluid bioadhesive for urinary fistula sealing.

Urinary fistulas, abnormal openings of a urinary tract organ, are serious complications and conventional management strategies are not satisfactory. For more effective and non-invasive fistula repair, fluid tissue adhesives or sealants have been suggested. However, conventional products do not provide a suitable solution due to safety problems and poor underwater adhesion under physiological conditions. Herein, we proposed a unique water-immiscible mussel protein-based bioadhesive (WIMBA) exhibiting strong underwater adhesion which was employed by two adhesion strategies of marine organisms; 3,4-dihydroxy-l-phenylalanine (DOPA)-mediated strong adhesion and water-immiscible coacervation. The developed biocompatible WIMBA successfully sealed ex vivo urinary fistulas and provided good durability and high compliance. Thus, WIMBA could be used as a promising sealant for urinary fistula management with further expansion to diverse internal body applications.

Salvianolic acid B exerts vasoprotective effects through the modulation of heme oxygenase-1 and arginase activities.

Salvia miltiorrhiza (Danshen), a traditional Chinese herbal medicine, is commonly used for the prevention and treatment of cardiovascular disorders including atherosclerosis. However, the mechanisms responsible for the vasoprotective effects of Danshen remain largely unknown. Salvianolic acid B (Sal B) represents one of the most bioactive compounds that can be extracted from the water-soluble fraction of Danshen. We investigated the effects of Danshen and Sal B on the inflammatory response in murine macrophages. Danshen and Sal B both induced the expression of heme oxygenase-1 (HO-1) and inhibited nitric oxide (NO) production and inducible NO synthase (iNOS) expression in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Inhibition of HO activity using Sn-protoporphyrin-IX (SnPP) abolished the inhibitory effect of Sal B on NO production and iNOS expression. Sal B increased macrophage arginase activity in a dose-dependent manner and diminished LPS-inducible tumor necrosis factor-α production. These effects were also reversed by SnPP. These data suggest that HO-1 expression plays an intermediary role in the anti-inflammatory effects of Sal B. In contrast to the observations in macrophages, Sal B dose-dependently inhibited arginase activity in murine liver, kidney, and vascular tissue. Furthermore, Sal B increased NO production in isolated mouse aortas through the inhibition of arginase activity and reduction of reactive oxygen species production. We conclude that Sal B improves vascular function by inhibiting inflammatory responses and promoting endothelium-dependent vasodilation. Taken together, we suggest that Sal B may represent a potent candidate therapeutic for the treatment of cardiovascular diseases associated with endothelial dysfunction.

Korean red ginseng (Panax ginseng) improves insulin sensitivity in high fat fed Sprague-Dawley rats.

Many studies have documented that ginseng has antidiabetic and antiobesity effects, but the mechanism of the effects has not been elucidated. The aim of this study was to determine the effect of Korean red ginseng (KRG, Panax ginseng) and investigate the mechanism of antidiabetic and antiobesity effects in obese insulin resistant animal models. Sprague-Dawley (SD) rats were divided into three groups: a control group (group I) fed a normal diet, another group (group II) fed only high fat diet (HFD) and a third group (group III) fed HFD with KRG (200 mg/kg, oral) for 18 weeks. The body weight, food intake, adipose tissues, liver, kidney, pancreas, adiponectin, and leptin were measured. Blood glucose, insulin tolerance test, and hyperinsulinemic euglycemic clamp test were investigated. A significant weight reduction, especially fat mass reduction, was observed in the KRG treated group. Increased insulin sensitivity was found in the KRG treated group. We observed increased insulin signalling, increased phosphorylation of IR, IRS-1, Akt, and membranous GLUT4 in muscle by Western blotting assay. In conclusion, KRG may have antidiabetic and antiobesity effects due to partly increased insulin sensitivity by increased adipokine and partly enhanced insulin signalling.

Studies on the safety of creatine supplementation.

Doubtful allegations of adverse effects of creatine supplementation have been released through the press media and through scientific publications. In the present review we have tried to separate the wheat from the chaff by looking for the experimental evidence of any such claims. Anecdotal reports from athletes have appeared on muscle cramp and gastrointestinal complaints during creatine supplementation, but the incidence of these is limited and not necessarily linked to creatine itself. Despite several unproved allegations, liver (enzymes, urea) and kidneys (glomerular filtration urea and albumin excretion rates) show no change in functionality in healthy subjects supplemented with creatine, even during several months, in both young and older populations. The potential effects (production of heterocyclic amines) of mutagenicity and carcinogenicity induced by creatine supplementation have been claimed by a French Sanitary Agency (AFSSA), which might put consumers at risk. Even if there is a slight increase (within the normal range) of urinary methylamine and formaldehyde excretion after a heavy load of creatine (20 g/day) this is without effect on kidney function. The search for the excretion of heterocyclic amines remains a future task to definitively exclude the unproved allegation made by some national agencies. We advise that high-dose (>3-5 g/day) creatine supplementation should not be used by individuals with pre-existing renal disease or those with a potential risk for renal dysfunction (diabetes, hypertension, reduced glomerular filtration rate). A pre-supplementation investigation of kidney function might be considered for reasons of safety, but in normal healthy subjects appears unnecessary.

Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats.

Ginseng has been reported to ameliorate hyperglycemia in experimental and clinical studies; however, its mechanism of action remains unclear. In this study, we investigated the metabolic effects and putative molecular mechanisms of Korean red ginseng (KRG, Panax ginseng) in animal models for type 2 diabetes mellitus (T2DM) and peripheral insulin-responsive cell lines. Korean red ginseng was administered orally at a dose of 200 mg/(kg d) to Otsuka Long-Evans Tokushima fatty rats for 40 weeks. Initially, chronic administration of KRG reduced weight gain and visceral fat mass in the early period without altering food intake. The KRG-treated Otsuka Long-Evans Tokushima fatty rats showed improved insulin sensitivity and significantly preserved glucose tolerance compared with untreated control animals up to 50 weeks of age, implying that KRG attenuated the development of overt diabetes. KRG promoted fatty acid oxidation by the activation of adenosine monophosphate-activated protein kinase (AMPK) and phosphorylation of acetyl-coenzyme A carboxylase in skeletal muscle and cultured C2C12 muscle cells. Increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, nuclear respiratory factor-1, cytochrome c, cytochrome c oxidase-4, and glucose transporter 4 by KRG treatment indicates that activated AMPK also enhanced mitochondrial biogenesis and glucose utilization in skeletal muscle. Although these findings suggest that KRG is likely to have beneficial effects on the amelioration of insulin resistance and the prevention of T2DM through the activation of AMPK, further clinical studies are required to evaluate the use of KRG as a supplementary agent for T2DM.

The effect of 4 weeks beta-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres.

Seven male students were supplemented with beta-alanine (beta-ALG) for 4 weeks (6.4 g day(-1)) and seven with a matching placebo (PLG). Subjects undertook 4 weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10 x 10 maximal 90 degrees extension and flexion contractions at 180 degrees /s using a Kin-Com isokinetic dynamometer, with 1 min rest between bouts. Muscle biopsies were taken from the vastus lateralis immediately before and at the end of the supplementation period. Following freeze drying muscle fibres were dissected and characterised by their MHC profile, as type I, IIa, IIx, or as hybrids of these. Carnosine was measured by HPLC. There was a significant increase in carnosine in both T and UT legs of the beta-ALG (9.63 +/- 3.92 mmol kg(-1) dry muscle and 6.55 +/- 2.36 mmol kg(-1) dry muscle respectively). There was a significant increase in the carnosine content of all fibre phentotypes, with no significant difference between types. There were no significant differences in the changes in muscle or in fibres between the T and UT legs. In contrast there was no significant change in the carnosine content in either the T or UT legs with placebo. The results indicate that 4 weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with beta-alanine supplementation, this was not further influenced by training. These findings suggest that beta-alanine availability is the main factor regulating muscle carnosine synthesis.

The effects of 10 weeks of resistance training combined with beta-alanine supplementation on whole body strength, force production, muscular endurance and body composition.

Carnosine (Carn) occurs in high concentrations in skeletal muscle is a potent physico-chemical buffer of H+ over the physiological range. Recent research has demonstrated that 6.4 g x day(-1) of beta-alanine (beta-ala) can significantly increase skeletal muscle Carn concentrations (M-[Carn]) whilst the resultant change in buffering capacity has been shown to be paralleled by significant improvements in anaerobic and aerobic measures of exercise performance. Muscle carnosine increase has also been linked to increased work done during resistance training. Prior research has suggested that strength training may also increase M-[Carn] although this is disputed by other studies. The aim of this investigation is to assess the effect of 10 weeks resistance training on M-[Carn], and, secondly, to investigate if increased M-[Carn] brought about through beta-ala supplementation had a positive effect on training responses. Twenty-six Vietnamese sports science students completed the study. The subjects completed a 10-week resistance-training program whilst consuming 6.4 g x day(-1) of beta-ala (beta-ALG) or a matched dose of a placebo (PLG). Subjects were assessed prior to and after training for whole body strength, isokinetic force production, muscular endurance, body composition. beta-Alanine supplemented subjects increased M-[Carn] by 12.81 +/- 7.97 mmol x kg(-1) dry muscle whilst there was no change in PLG subjects. There was no significant effect of beta-ala supplementation on any of the exercise parameters measured, mass or % body fat. In conclusion, 10 weeks of resistance training alone did not change M-[Carn].