TIMP2 deficient mice develop accelerated osteoarthritis via promotion of angiogenesis upon destabilization of the medial meniscus

Vascular invasion into the normally avascular articular surface is a hallmark of advanced osteoarthritis (OA). In this study, we demonstrated that the expression of tissue inhibitor of metalloproteinases-2 (TIMP2), an anti-angiogenic factor, was present at high levels in normal articular chondrocytes, and was drastically decreased shortly after destabilization of the medial meniscus (DMM). We also investigated the anti-angiogenic properties of TIMP2 via knockout. We hypothesized that the loss of TIMP2 could accelerate osteoarthritis development via promotion of angiogenesis. Loss of TIMP2 led to increased periarticular vascular formation 1 month post DMM, compared to wild-type mice, and did so without altering the expression pattern of matrix metalloproteinases and vascular endothelial growth factors. The increased vascularization eventually resulted in a severe degeneration of the articular surface by 4 months post DMM. Our findings suggest that reduction of TIMP2 levels and increased angiogenesis are possible primary events in OA progression. Inhibiting or delaying angiogenesis by TIMP2 expression or other anti-angiogenic therapies could improve OA prevention and treatment.     

Correlation between body composition and risk factors for cardiovascular disease and metabolic syndrome

Body mass index (BMI) is an important diagnostic tool for determining obesity; however, while BMI reflects the influence of body height over body weight, it does not reveal body fat percentage (BF%). We explored whether BF% correlated with risk factors for cardiovascular disease and metabolic syndrome and whether metabolically obese, normal weight people were at risk for these diseases. A total of 2,867 healthy volunteers participated in this study. Blood pressure, height, weight, waist circumference, BMI, BF%, lipid profile, fasting glucose, uric acid, and lifestyle factors were collected from healthy subjects during their annual health examinations. In both males and females, BF% correlated positively with BMI and waist circumference. Participants were divided into three groups according to BF% and data were compared between groups. The results suggest that BF% correlates with risk factors for cardiovascular disease and metabolic syndrome for both men and women, and that BF% may be a useful predictor of risk, particularly in metabolically obese, normal weight individuals. ? 2012 International Union of Biochemistry and Molecular Biology, Inc.     

Probiotics-containing yogurts suppress Helicobacter pylori load and modify immune response and intestinal microbiota in the Helicobacter pylori-infected children

Background: The benefits of probiotics to the pediatric Helicobacter pylori infection remain uncertain. We tested whether the H. pylori‐infected children have an altered gut microflora, and whether probiotics‐containing yogurt can restore such change and improve their H. pylori‐related immune cascades. Methods: We prospectively included 38 children with H. pylori infection confirmed by a positive ¹³C‐urea breath test (UBT) and 38 age‐ and sex‐matched noninfected controls. All of them have provided the serum and stool samples before and after 4‐week ingestion of probiotics‐containing yogurt. The serum samples were tested for the TNF‐α, IL‐10, IL‐6, immunoglobulin (Ig) A, G, E, pepsinogens I and II levels. The stool samples were tested for the colony counts of Bifidobacterium spp. and Escherichia coli. The follow‐up UBT indirectly assessed the H. pylori loads after yogurt usage. Results: The H. pylori‐infected children had lower fecal Bifidobacterium spp. count (p = .009), Bifidobacterium spp./E. coli ratio (p = .04), serum IgA titer (p = .04), and pepsinogens I/II ratio (p < .001) than in controls. In the H. pylori‐infected children, 4‐week yogurt ingestion reduced the IL‐6 level (p < .01) and H. pylori loads (p = .046), but elevated the serum IgA and pepsinogen II levels (p < .001). Moreover, yogurt ingestion can improve the childhood fecal Bifidobacterium spp./E. coli ratio (p = .03). Conclusions: The H. pylori‐infected children have a lower Bifidobacterium microflora in gut. The probiotics‐containing yogurt can offer benefits to restore Bifidobacterium spp./E. coli ratio in children and suppress the H. pylori load with increment of serum IgA but with reduction in IL‐6 in H. pylori‐infected children.     

P wave dispersion and maximum p wave duration are independently associated with rapid renal function decline

The P wave parameters measured by 12-lead electrocardiogram (ECG) are commonly used as noninvasive tools to assess for left atrial enlargement. There are limited studies to evaluate whether P wave parameters are independently associated with decline in renal function. Accordingly, the aim of this study is to assess whether P wave parameters are independently associated with progression to renal end point of ≥25% decline in estimated glomerular filtration rate (eGFR). This longitudinal study included 166 patients. The renal end point was defined as ≥25% decline in eGFR. We measured two ECG P wave parameters corrected by heart rate, i.e. corrected P wave dispersion (PWdisperC) and corrected P wave maximum duration (PWdurMaxC). Heart function and structure were measured from echocardiography. Clinical data, P wave parameters, and echocardiographic measurements were compared and analyzed. Forty-three patients (25.9%) reached renal end point. Kaplan-Meier curves for renal end point-free survival showed PWdisperC > median (63.0 ms) (log-rank P = 0.004) and PWdurMaxC > median (117.9 ms) (log-rank P<0.001) were associated with progression to renal end point. Multivariate forward Cox-regression analysis identified increased PWdisperC (hazard ratio [HR], 1.024; P = 0.001) and PWdurMaxC (HR, 1.029; P = 0.001) were independently associated with progression to renal end point. Our results demonstrate that increased PWdisperC and PWdurMaxC were independently associated with progression to renal end point. Screening patients by means of PWdisperC and PWdurMaxC on 12 lead ECG may help identify a high risk group of rapid renal function decline.     

Scavenging effect of benzophenones on the oxidative stress of skeletal muscle cells.

Benzophenone is an ultraviolet (UV)-absorbing agent that has been used in industry and medicine for more than 30 years. Consumers of cosmetics and sunscreens containing UV-absorbers are exposed to benzophenones on a daily basis, owing to the widespread use of these compounds. However, the efficacy of these compounds as scavengers of oxidative stress is still not well established. In the present study, we investigate the antioxidative capacity of six sunscreen benzophenone compounds. A primary myoblast culture was mixed in vitro with 100 microM menadione. The cytotoxic effect by menadione-induced oxidative stress was monitored by the lucigenin- or luminol-amplified chemiluminescence, methylthiotetrazole (MTT) assay, and the antioxidative effects of various benzophenone compounds were evaluated. The results showed that the addition of menadione can induce oxidative stress on myoblasts by superoxide and hydrogen peroxide production, which can be eradicated by superoxide dismutase (SOD) and catalase, respectively, in a dose-dependent mode. The catalase has a protective effect on the cytotoxicity induced by menadione as measured by the MTT assay, while the SOD does not. The selected benzophenones also have a significant scavenging effect on the menadione-induced cell death on the myoblasts. The ortho-dihydroxyl structure and other hydroxy groups in the same ring have a stronger scavenging effect on the superoxide anion on myoblasts; thus, a stable penoxy radical may be formed. The mechanism of this effect remains to be clarified.     

Plasma status of selected minerals in hypertensive men with and without insulin resistance

The altered plasma statuses of selected minerals (Ca, Mg, Cu, Zn) have been noted in a cluster of insulin resistance syndromes, including hypertension and diabetes mellitus. The differences in plasma values of these minerals in hypertensive men with and without insulin resistance, as evaluated by an insulin suppression test, were investigated. The results showed that the plasma values of determined minerals at fasting, 2 h after an oral glucose challenge, and after the insulin suppression test did not markedly differ between hypertensive subjects with and without insulin resistance. However, hypertensive subjects had significantly lower plasma Ca values at fasting and 2h after an oral glucose load, and higher fasting plasma Zn values, than normotensive controls. Hypertensive subjects also had higher steady-state plasma glucose values, higher Zn and lower Mg and Cu values after the insulin suppression test, when compared with controls. The present study suggests that altered plasma status of selected minerals in hypertension cannot be totally ascribed to the coexhibition of insulin resistance.     

Temperature sensitive nitrogen fixation mutants of Azotobacter vinelandii

Summary Temperature-sensitive nitrogen fixation mutants of Azotobacter vinelandii were obtained by nitrosoguanidine mutagenesis and penicillin selection. The mutants were unable to grow on N₂ at 39° but grew normally at 30° on N₂ and at both temperatures in the presence of metabolizable nitrogen compounds. Growth experiments and assays of whole cells for nitrogenase activity separated the mutants into two classes: 1. mutants in which the nitrogenase activity present in cells grown at 30° was unaffected by a shift to 39°, and 2. mutants which lost their nitrogen fixation activity after such a temperature shift. Assays of cell-free extracts of the second class of mutants showed that in all cases tested the enzymatic activity of the nitrogenase complex itself was not affected by the mutation. These mutants might therefore contain some other temperature-sensitive proteins specifically involved in nitrogen fixation.