Continued expansion of indications for sodium-glucose cotransporter-2 inhibitors increases importance of evaluating cardiovascular and kidney efficacy and safety of empagliflozin in patients with ...type 2 diabetes compared to similar therapies.
The EMPRISE Europe and Asia study is a non-interventional cohort study using data from 2014–2019 in seven European (Denmark, Finland, Germany, Norway, Spain, Sweden, United Kingdom) and four Asian (Israel, Japan, South Korea, Taiwan) countries. Patients with type 2 diabetes initiating empagliflozin were 1:1 propensity score matched to patients initiating dipeptidyl peptidase-4 inhibitors. Primary endpoints included hospitalization for heart failure, all-cause mortality, myocardial infarction and stroke. Other cardiovascular, renal, and safety outcomes were examined.
Among 83,946 matched patient pairs, (0·7 years overall mean follow-up time), initiation of empagliflozin was associated with lower risk of hospitalization for heart failure compared to dipeptidyl peptidase-4 inhibitors (Hazard Ratio 0·70; 95% CI 0.60 to 0.83). Risks of all-cause mortality (0·55; 0·48 to 0·63), stroke (0·82; 0·71 to 0·96), and end-stage renal disease (0·43; 0·30 to 0·63) were lower and risk for myocardial infarction, bone fracture, severe hypoglycemia, and lower-limb amputation were similar between initiators of empagliflozin and dipeptidyl peptidase-4 inhibitors. Initiation of empagliflozin was associated with higher risk for diabetic ketoacidosis (1·97; 1·28 to 3·03) compared to dipeptidyl peptidase-4 inhibitors. Results were consistent across continents and regions.
Results from this EMPRISE Europe and Asia study complements previous clinical trials and real-world studies by providing further evidence of the beneficial cardiorenal effects and overall safety of empagliflozin compared to dipeptidyl peptidase-4 inhibitors.
Serum uric acid is associated with cardiovascular disease. However, the independent role of uric acid in the development of cardiovascular disease is uncertain. This study examined the ...cross-sectional association of serum uric acid level with microalbuminuria among 6771 subjects without diabetes or hypertension. Blood pressure was categorized as prehypertension (systolic blood pressure, 120 to 140 mm Hg or diastolic blood pressure, 80 to 90 mm Hg) and normotension (systolic blood pressure, <120 mm Hg and diastolic blood pressure, <80 mm Hg). Microalbuminuria was found in 4.0% of normotensive subjects (n=4819) and in 7.9% of prehypertensive subjects (n=1952). Prehypertensive subjects with microalbuminuria had higher uric acid level than those with normoalbuminuria (men, 387 68 mmol/L versus 371 69 mmol/L; P=0.017; women 286 56 mmol/L versus 262 54 mmol/L; P=0.006). However, the difference in serum uric acid level according to the presence or absence of microalbuminuria was not found in the normotensive group. Multiple logistic regression models showed that, in the prehypertensive group, after adjustment for other cardiovascular risk factors, the highest uric acid quartile entailed >2 times greater risk for microalbuminuria than the lowest quartile in both men (odds ratio, 2.12; 95% CI, 1.16 to 3.87) and women (odds ratio, 3.36; 95% CI, 1.17 to 9.69). In the normotensive group, serum uric acid quartile did not show the independent association with microalbuminuria. In conclusion, serum uric acid level was strongly associated with microalbuminuria in prehypertensive subjects.
XRD results showed that TiO2 thin film calcined at 300 C was amorphous, and transformed into the anatase phase at 400 C, and further into rutile phase at 1000 C. The phase transformation temperature ...was dependent upon the concentration of catalyst HCl. The crystallite size of TiO2 thin films was increased with increasing calcination temperature. The micro-particles in the films grew by intra-agglomerate densification below 1000 C, whereas they grew by inter-agglomerate densification above 1000 C. The transmittance of the films calcined at 1000 and 1100 C was reduced significantly in the wavelength range of about 300-700 nm due to the change of crystallite phase and composition in the films. The refractive index of TiO2 thin films was increased with increasing calcination temperature, and the film thickness and the porosity of TiO2 thin films were decreased. 23 refs.
Factors involved in inflammation are linked with those critical for bone remodeling. We examined the association between serum high sensitivity C-reactive protein (hsCRP) levels and bone mineral ...density (BMD) in healthy women. Serum concentrations of hsCRP and total alkaline phosphatase (ALP) were measured in premenopausal ( n =3,662) and postmenopausal ( n =1,031) women aged 30 years or older. BMD was measured at the femoral neck and lumbar spine using dual energy X-ray absorptiometry. According to the WHO definition, osteopenia was diagnosed at -2.5< T -score < -1.0 SD, and osteoporosis was diagnosed at T -score < or = -2.5 SD at any sites. Compared with normal subjects, log-transformed serum hsCRP levels were higher in osteopenic and osteoporotic subjects (all, P < 0.001) with linearity ( P for trend <0.001), after adjustment for age, BMI and menopausal status. Menopausal status did not have a significant interaction on the association ( P =0.457). In both premenopausal and postmenopausal women, serum total ALP levels were higher in the subjects with higher hsCRP quintiles than those with the lowest quintile (all, P for trend < 0.001). Multivariate-adjusted odds ratio (OR) for osteoporosis and osteopenia were 1.35 (95% CI, 1.08 to 1.68) in the highest hsCRP quintile of premenopausal women, and OR for osteoporosis was 1.54 (95% CI, 1.10 to 2.53) in the highest hsCRP quintile of postmenopausal women. These findings suggest that subclinical systemic inflammation may be associated with bone turnover rate and bone mass in healthy women.
Epigallocatechin gallate (EGCG), a major constituent of green tea, is a potent free radical scavenger. The purpose of this study was to verify whether EGCG reduces focal ischemia/reperfusion-induced ...brain injury in a rat model. Male Sprague–Dawley rats were anesthetized with chloral hydrate (400 mg/kg, i.p.) and subjected to a middle cerebral artery 2 h occlusion and then a 24-h reperfusion. The EGCG (25 mg and 50 mg/kg, i.p.) or vehicle was administered immediately after reperfusion. Twenty-four hours after reperfusion, infarction size, levels of oxidative stress markers (malondialdehyde and oxidized/total glutathione ratio) in the brain and neurological deficits were evaluated. The dose of 50 mg/kg of EGCG significantly reduced the infarction volume (9.9±3.2%) as compared to those (45.6±5.3%, 34.5±7.8%) of the control group and the EGCG 25 mg/kg treated group (p<0.01). The dose of 50 mg/kg of EGCG significantly reduced the neurological deficit total score (5.2±1.7) as compared to those (9.5±1.2, 8.5±2.5) of the control group and the EGCG 25 mg/kg treated group (p<0.05). The dose of 50 mg/kg of EGCG significantly attenuated the level of malondialdehyde and the level of oxidized/total glutathione ratio (281±66 nmol/g and 0.48±0.03) as compared to the those (415±46 nmol/g and 0.64±0.05, 381±51 nmol/g and 0.61±0.06) of the control group and the EGCG 25 mg/kg treated group (p<0.05). These results demonstrate the anti-oxidant effects of EGCG (50 mg/kg) in a rat model of transient focal ischemia, which is a likely explanation for EGCG's neuroprotective effects.
We investigated the formation of thermoresponsive gold nanoparticle/poly(N‐isopropylacrylamide) (AuNP/PNIPAAm) core/shell hybrid structures by surface‐initiated, atom transfer radical polymerization ...(SI‐ATRP) in aqueous media and the effect of cross‐linking on the thermoresponsiveness of the AuNP/PNIPAAm hybrids. The disulfide containing an ATRP initiator was attached onto AuNPs and the monomer, NIPAAm, was polymerized from the surface of AuNPs in the absence or presence of a cross‐linker, ethylene diacrylate, in aqueous media at room temperature. The resulting brush‐type and cross‐linked AuNP/PNIPAAm hybrids were characterized by Fourier‐transform infrared spectroscopy, transmission electron microscopy, and variable temperature dynamic light scattering.
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed ...by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries’ progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1‐year‐olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year‐to‐year decrease in new HCV‐ and HBV‐related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
Background
Alcohol use affecting the risk of type 2 diabetes mellitus (T2DM) is poorly identified as well as the role of brain‐derived neurotrophic factor (BDNF), ghrelin, and leptin in alcohol ...dependence with T2DM. We tested the hypothesis that alcohol abstinence affects diabetes‐related factors and BDNF, ghrelin, and leptin secretions in alcohol‐dependent patients with glucose intolerance.
Methods
A total of 64 male alcohol‐dependent patients were classified into normal glucose tolerance (NGT), pre‐diabetes mellitus (pre‐DM), and diabetes mellitus (DM) groups according to a 75‐g oral glucose tolerance test (OGTT). All participants got alcohol dependence rehabilitation treatment for 30 days, and then we compared changes in BDNF, ghrelin, and leptin between pre‐ and post‐alcohol abstinence.
Results
After alcohol abstinence, both pre‐DM and DM groups had significantly decreased levels of fasting glucose. All 3 groups exhibited elevated ghrelin levels and reduced leptin levels, but BDNF levels were significantly increased only in the pre‐DM group. The pre‐DM group had large increases in BDNF and ghrelin levels compared with those of the NGT group. Moreover, decreases in homeostasis model assessment of insulin resistance (HOMA‐IR), fasting glucose, and leptin levels in the DM group were larger than those in the NGT group.
Conclusions
Alcohol abstinence might influence diabetes‐related factors of alcohol‐dependent patients with glucose intolerance. Further, BDNF, ghrelin, and leptin differently affect this improvement, depending on the stage of DM. In the pre‐DM group, elevated BDNF and ghrelin levels are likely to influence insulin sensitivity, insulin resistance, and fasting glucose levels. Further, reduced leptin levels after abstinence might be related to improved glucose kinetics in patients with diabetes.
An extracellular tannase (tannin acyl hydrolase) was isolated from Paecilomyces variotii and purified from cell-free culture filtrate using ammonium sulfate precipitation followed by ion exchange and ...gel filtration chromatography. Fractional precipitation of the culture filtrate with ammonium sulfate yielded 78.7% with 13.6-folds purification, and diethylaminoethyl-cellulose column chromatography and gel filtration showed 19.4-folds and 30.5-folds purifications, respectively. Molecular mass of tannase was found 149.8 kDa through native polyacrylamide gel electrophoresis (PAGE) analysis. Sodium dodecyl sulphate-PAGE revealed that the purified tannase was a monomeric enzyme with a molecular mass of 45 kDa. Temperature of 30 to 50°C and pH of 5.0 to 7.0 were optimum for tannase activity and stability. Tannase immobilized on alginate beads could hydrolyze tannic acid even after extensive reuse and retained about 85% of the initial activity. Thin layer chromatography, high performance liquid chromatography, and ¹H-nuclear magnetic resonance spectral analysis confirmed that gallic acid was formed as a byproduct during hydrolysis of tannic acid.
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