Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings

Time-dependent changes in membrane excitability during glucose-induced bursting activity in pancreatic β cells

In our companion paper, the physiological functions of pancreatic β cells were analyzed with a new β-cell model by time-based integration of a set of differential equations that describe individual reaction steps or functional components based on experimental studies. In this study, we calculate steady-state solutions of these differential equations to obtain the limit cycles (LCs) as well as the equilibrium points (EPs) to make all of the time derivatives equal to zero. The sequential transitions from quiescence to burst–interburst oscillations and then to continuous firing with an increasing glucose concentration were defined objectively by the EPs or LCs for the whole set of equations. We also demonstrated that membrane excitability changed between the extremes of a single action potential mode and a stable firing mode during one cycle of bursting rhythm. Membrane excitability was determined by the EPs or LCs of the membrane subsystem, with the slow variables fixed at each time point. Details of the mode changes were expressed as functions of slowly changing variables, such as intracellular [ATP], [Ca2+], and [Na+]. In conclusion, using our model, we could suggest quantitatively the mutual interactions among multiple membrane and cytosolic factors occurring in pancreatic β cells

Ionothermal Synthesis of a Novel 3D Cobalt Coordination Polymer with a Uniquely Reported Framework: [BMI] 2

The framework of [RMI]2[Co2(BTC)2(H2O)2] (RMI = 1-alkyl-3-methylimidazolium, alkyl; ethyl (EMI); propyl (PMI); butyl (BMI)), which has uniquely occurred in ionothermal reactions of metal salts and H3BTC (1,3,5-benzenetricarboxylic acid), an organic ligand, reappeared in this work. Ionothermal reaction of cobalt acetate and H3BTC with [BMI]Br ionic liquid as the reaction medium yielded the novel coordination polymer [BMI]2[Co2(BTC)2(H2O)2] (compound B2). Similar ionothermal reactions with different [EMI]Br and [PMI]Br as the reaction media have been previously reported to produce [EMI]2[Co3(BTC)2(OAc)2] (compound A1) and [PMI]2[Co2(BTC)2(H2O)2] (compound B1), respectively. In contrast with the trinuclear secondary building unit of A1, the framework structure of B1 and B2 consists of dinuclear secondary building units in common, but with subtle distinction posed by the different size of the incorporated cations. These structural differences amidst the frameworks showed interesting aspects, including guest and void volume, and were used to explain the chemical trend observed in the system. Moreover, the physicochemical properties of the newly synthesized compound have been briefly discussed

Strong ferromagnetism in Pt-coated ZnCoO: The role of interstitial hydrogen

We observed strong ferromagnetism in ZnCoO as a result of high concentration hydrogen absorption. Coating ZnCoO with Pt layer, and ensuing hydrogen treatment with a high isostatic pressure resulted in a highly increased carrier concentration of 10(21)/cm(3). This hydrogen treatment induced a strong ferromagnetism at low temperature that turned to superparamagnetism at about 140 K. We performed density functional method computations and found that the interstitial H dopants promote the ferromagnetic ordering between scattered Co dopants. On the other hand, interstitial hydrogen can decrease the magnetic exchange energy of Co-H-Co complexes, leading to a reduction in the blocking temperature.open7

Predictive and protective role of high-density lipoprotein cholesterol in acute myocardial infarction

Background: It is unclear whether high-density lipoprotein cholesterol (HDL-C) level predicts cardiovascular events and has a protective effect in patients with acute myocardial infarction (AMI) undergo- ing percutaneous coronary intervention (PCI) and statin treatment. Methods: A total of 15,290 AMI patients receiving statins were selected from the Korean Myocardial Infarction Registry. Baseline HDL-C level was used to identify patients with low (group A), normal (group B), and high (group C) HDL-C levels according to the Adult Treatment Panel III criteria. Clinical outcomes were compared in propensity-adjusted and matched cohorts. The primary endpoint was a composite of cardiovascular death and recurrent myocardial infarction.  Results: At the median follow-up of 11.5 months, the primary endpoint occurred in 2.7% (112/4098), 1.4% (54/3910), and 1.2% (8/661) of patients in groups A, B, and C, respectively. In the propensity- -adjusted cohort, low HDL-C level increased the risk of primary endpoint (hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.274–2.417, p = 0.001), whereas high HDL-C level did not reduce this risk (HR 0.562, 95% CI 0.275–1.146, p = 0.113). In the propensity-matched cohort, low HDL-C level increased the risk of primary endpoint (HR 1.716, 95% CI 1.210–2.434, p = 0.002), whereas high HDL-C level reduced this risk (HR 0.449, 95% CI 0.214–0.946, p = 0.035).  Conclusions: In AMI patients treated with PCI and statins, low HDL-C level increases the risk of cardiovascular death and recurrent myocardial infarction, whereas high HDL-C level likely reduces the risk of cardiovascular events, especially for ST-elevation myocardial infarction.

The Use of Complementary and Alternative Medicine in a General Population in South Korea: Results from a National Survey in 2006

The purpose of this survey was to obtain information on the prevalence, costs, and patterns of use of complementary and alternative medicine (CAM) in a general population in the Republic of Korea. In 2006, we conducted nationwide and population-weighted personal interviews with 6,021 adults ranging from 30 to 69 yr of age; the final sample consisted of 3,000 people with a 49.8% response rate. In addition to their general socio-demographics, the respondents were asked about their use of CAM during the previous 12-month period, costs, sources of information, and reasons for use. The prevalence of use overall was 74.8%, while biologically based CAM therapies were the most likely type of use (65.4%). The median annual out-of-pocket expenditures for CAM therapies was about US$203. The primary reason for using CAM was for disease prevention and health promotion (78.8%). The main source of advice about CAM therapies use was most likely to be from family and friends (66.9%). Our study suggests that CAM use has been and continues to be very popular in South Korea. Conventional western medical doctors and governments should obtain more evidence and become more interested in CAM therapies

PPARγ Agonist and Angiotensin II Receptor Antagonist Ameliorate Renal Tubulointerstitial Fibrosis

The peroxisome proliferator activated receptor (PPAR)γ agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARγ agonist and interaction with angiotensin receptor antagonist in the unilateral ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT), pioglitazone treatment, L158809 treatment, and L158809+ pioglitazone treatment. On day 14, CONT mice showed severe fibrosis and all treated mice showed decreased fibrosis. The immunohistochmistry of PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT. PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of TGF-β1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the pioglitazone inhibited tubulointerstitial fibrosis, however, the synergism between pioglitazone and L158809 is not clear. Considering decreased expression of PAI-1 and TGF-β/Smad2 in the treated groups, PAI-1 and TGF-β are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARγ agonist might be used in the treatment of renal fibrotic disease

The heme oxygenase-1 genotype is a risk factor to renal impairment of IgA nephropathy at diagnosis, which is a strong predictor of mortality

The induction of heme oxygenase-1 (HO-1) ameliorates oxidative stress and inflammatory process, which play important roles in IgA nephropathy. We hypothesized length polymorphism in the promoter region of the HO-1 gene, which is related to the level of gene transcription, is associated with disease severity of IgA nephropathy. The subjects comprised 916 patients with IgA nephropathy and gene data. Renal impairment was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) at diagnosis. The short (S: 28) (GT) repeats in the HO-1 gene was determined. The frequencies of S/S, S/M, M/M, S/L, L/M, and L/L genotypes were 7.2%, 6.9%, 3.1%, 30.8%, 22.7%, and 29.4%, respectively. The baseline characteristics were not different. In the S/S genotypic group, the renal impairment rate was 18.2%, which was lower than 32.2% in the group with M/M, L/M, or L/L genotype. The odds ratio of renal impairment in S/S genotype, compared to that in M/M, L/M, or L/L genotype, was 0.216 (95% confidence interval, 0.060-0.774, p=0.019). The HO-1 gene promoter length polymorphism was related to the renal impairment of IgA nephropathy at diagnosis, which is an important risk factor for mortality in IgA nephropathy patients