Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas

The objective of this study is to examine the efficacy and tolerability of miglitol with respect to improving glycemic control in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment. This was a randomized, double-blinded, placebo-controlled, multicenter study. A total of 105 patients were randomized to receive 24 weeks of treatment with miglitol (n = 52; titrated from 50 mg to 100 mg 3 times daily) or placebo (n = 53). Concomitant sulfonylurea treatment and diet remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline at 24 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and postprandial serum insulin (PSI). The miglitol treatment group showed significantly greater reductions in HbA1c and PPG levels compared with the placebo group. With respect to adverse events, abdominal discomfort, diarrhea, and hypoglycemia occurred with similar frequency in both groups. Results of this study indicate that miglitol significantly improves metabolic control in Chinese patients with type 2 diabetes mellitus. Miglitol is safe and well tolerated, with the exception of abdominal discomfort. Therefore, miglitol may be a useful adjuvant therapy for Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment

Differential relationships of family drinking with alcohol expectancy among urban school children

<p>Abstract</p> <p>Background</p> <p>Positive alcohol outcome expectancy has consistently been linked with problematic drinking, but there is little population-based evidence on its role on early stages of drinking in childhood. The present study seeks to understand the extent to which drinking of family members is differentially associated with the endorsement of alcohol expectancy in late childhood.</p> <p>Methods</p> <p>A representative sample of 4th and 6th graders (N = 2455) drawn from 28 public schools in an urban region of Taiwan completed a self-administered paper-and-pencil questionnaire. Each student provided information on alcohol expectancy, drinking experiences, and individual and family attributes. Complex survey analyses were performed to evaluate the relationship, with stratification by children's alcohol drinking history.</p> <p>Results</p> <p>An estimated 29% of the 4^thgraders and 43% of the 6^thgraders had initiated alcohol consumption (over 40% of them had drank on three or more occasions). Alcohol drinking-related differences appear in both the endorsement and the correlates of alcohol expectancy. Positive alcohol expectancy was strongly associated with family drinking, particularly the dimension of "enhanced social behaviors"; negative alcohol expectancy was inversely associated with drinking frequency. Among alcohol naïve children, significant connections appear between paternal drinking and three dimensions of positive alcohol expectancy (i.e., enhanced social behaviors:β_wt= 0.15, promoting relaxation or tension reduction:β_wt= 0.18, and global positive transformation:β_wt= 0.22).</p> <p>Conclusions</p> <p>Individual tailored strategies that address family influences on alcohol expectancy may be needed in prevention programs targeting drinking behaviors in children.</p

A Dimer of the Toll-Like Receptor 4 Cytoplasmic Domain Provides a Specific Scaffold for the Recruitment of Signalling Adaptor Proteins

The Toll-like receptor 4 (TLR4) is a class I transmembrane receptor expressed on the surface of immune system cells. TLR4 is activated by exposure to lipopolysaccharides derived from the outer membrane of Gram negative bacteria and forms part of the innate immune response in mammals. Like other class 1 receptors, TLR4 is activated by ligand induced dimerization, and recent studies suggest that this causes concerted conformational changes in the receptor leading to self association of the cytoplasmic Toll/Interleukin 1 receptor (TIR) signalling domain. This homodimerization event is proposed to provide a new scaffold that is able to bind downstream signalling adaptor proteins. TLR4 uses two different sets of adaptors; TRAM and TRIF, and Mal and MyD88. These adaptor pairs couple two distinct signalling pathways leading to the activation of interferon response factor 3 (IRF-3) and nuclear factor κB (NFκB) respectively. In this paper we have generated a structural model of the TLR4 TIR dimer and used molecular docking to probe for potential sites of interaction between the receptor homodimer and the adaptor molecules. Remarkably, both the Mal and TRAM adaptors are strongly predicted to bind at two symmetry-related sites at the homodimer interface. This model of TLR4 activation is supported by extensive functional studies involving site directed mutagenesis, inhibition by cell permeable peptides and stable protein phosphorylation of receptor and adaptor TIR domains. Our results also suggest a molecular mechanism for two recent findings, the caspase 1 dependence of Mal signalling and the protective effects conferred by the Mal polymorphism Ser180Leu

AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells

Upon activation, B cells divide, form a germinal center, and express the activation induced deaminase (AID), an enzyme that triggers somatic hypermutation of the variable regions of immunoglobulin (Ig) loci. Recent evidence indicates that at least 25% of expressed genes in germinal center B cells are mutated or deaminated by AID. One of the most deaminated genes, c-Myc, frequently appears as a translocation partner with the Ig heavy chain gene (Igh) in mouse plasmacytomas and human Burkitt's lymphomas. This indicates that the two genes or their double-strand break ends come into close proximity at a biologically relevant frequency. However, the proximity of c-Myc and Igh has never been measured in germinal center B cells, where many such translocations are thought to occur. We hypothesized that in germinal center B cells, not only is c-Myc near Igh, but other mutating non-Ig genes are deaminated by AID because they are near Ig genes, the primary targets of AID. We tested this “collateral damage” model using 3D-fluorescence in situ hybridization (3D-FISH) to measure the distance from non-Ig genes to Ig genes in germinal center B cells. We also made mice transgenic for human MYC and measured expression and mutation of the transgenes. We found that there is no correlation between proximity to Ig genes and levels of AID targeting or gene mutation, and that c-Myc was not closer to Igh than were other non-Ig genes. In addition, the human MYC transgenes did not accumulate mutations and were not deaminated by AID. We conclude that proximity to Ig loci is unlikely to be a major determinant of AID targeting or mutation of non-Ig genes, and that the MYC transgenes are either missing important regulatory elements that allow mutation or are unable to mutate because their new nuclear position is not conducive to AID deamination

生物骨傳導性骨水泥促進前交叉韌帶重建術腱骨癒合的研究進展(英文)

近10年來, 應用軟組織移植物行前交叉韌帶重建術越來越普遍。手術的遠期療效主要取決於肌腱移植物能否在骨隧道內達到堅強的腱- 骨癒合。但是, 目前面臨的問題是肌腱移植物在骨隧道內獲得腱- 骨癒合所需要的時間相當長。研究發現, 在腱- 骨界面局部應用生物骨傳導性的骨水泥能有效地促進肌腱移植物的骨癒合。這類骨水泥主要是磷酸鈣。本文就生物骨傳導性骨水泥促進前交叉韌帶重建術腱- 骨癒合的研究進展作一綜述。The utility of soft tissue autograft (hamstring autograft) for ACL reconstruction has grown in popularity in the past 10 years. The long-term clinical outcome is depended on the osteointegration of the tendon graft within the bone tunnel(tendon-bone healing).However, one of the most concerned limitations of soft tissue grafts in ACL reconstruction is that it needs an extremely long time to develop a secure tendon-bone healing. It is reported that local application of osteoconductive bone cements seems to be a promising strategy to enhance tendon-bone healing in ACL reconstruction animal models. Such osteoconductive bone cements are mainly calcium phosphate-based cements. The present paper reviewed the relative papers and tried to elucidate the progress in this research area.link_to_OA_fulltex

Sulfasalazine inhibits inflammation and fibrogenesis in pancreas via NF-&kappa;B signaling pathway in rats with oxidative stress-induced pancreatic injury

Ya-Ru Wang,1,* Fei-Long Tian,2,* Ming-Xian Yan,1 Jin-Hua Fan,1 Li-Yun Wang,1 Rong-Guang Kuang,1 Yan-Qing Li3 1Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, 2Shandong University School of Medicine, 3Department of Gastroenterology, Qilu Hospital, Shandong University, Ji&rsquo;nan, Shandong Province, People&rsquo;s Republic of China *These authors contributed equally to this work Background: Pathogenesis and effective therapeutics of chronic pancreatic inflammation and fibrosis remain uncertain.Purpose: To investigate the effects of sulfasalazine (SF) on pancreatic inflammation and fibrogenesis.Methods: Chronic pancreatic injury in rats was induced by diethyldithiocarbamate (DDC) and interfered by SF through intraperitoneal injection. The rats were divided into five groups: group&nbsp;N, normal control group, rats were treated with dilated water only; group DS1, rats received SF (10 mg/kg) 2 hours before DDC treatment; group DS2, rats were treated with DDC and then SF (100 mg/kg, twice a week); group DS3, rats were treated with DDC, then SF (100 mg/kg, thrice a week); and group DDC, rats were treated with DDC only. Pancreatic inflammation and fibrosis were determined by hematoxylin and eosin staining and Sirius red staining. The genes and proteins related to NF-&kappa;B pathway and fibrogenesis including NF-&kappa;B/p65, TNF-&alpha;, ICAM-1, &alpha;-SMA, and Con 1 were detected by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blotting.Results: Rats in the DDC and DS1 groups showed the highest histological scores after DDC treatment, but the scores of DS2 and DS3 groups decreased significantly when compared with the DDC group. Sirius red staining showed collagen formation clearly in DDC and DS1 rats rather than in DS2 and DS3 rats. NF-&kappa;B/p65, ICAM-1, and &alpha;-SMA were strongly expressed in DDC and DS1 rats, while DS2 and DS3 rats showed mild to moderate expression by immunohistochemistry. Reverse tran&shy;scription polymerase chain reaction showed increased levels of NF-&kappa;B/p65, ICAM-1, TNF-&alpha;, &alpha;-SMA, and Con 1 mRNA in DDC and DS1 rats in comparison to normal controls. The mRNA levels of these molecules in DS2 and DS3 rats were significantly lower than those in DS1 and DDC rats. Western blotting demonstrated that the NF-&kappa;B/p65, ICAM-1, and &alpha;-SMA expressions in pancreatic tissues of the rats of the DDC group were more clear than those of the normal control, DS2, and DS3 rats.Conclusion: SF inhibits pancreatic inflammation and fibrogenesis via NF-&kappa;B signaling pathway. Keywords: sulfasalazine, pancreatic injury, inflammation, fibrogenesis, NF-&kappa;

EFFECTS OF ANISODINE ON MEMORY

&lt;正&gt; Anisodine(AT_3)is a new alkaloid isolatedfrom Scopolia tangutica,Anisodus tanguticus,a plant of Solauaeeae family,collected fromMt.Tanggute.AT_3 has anticholinergic property.The influences of AT_3 on memory behavior,hip-pocampal electrical activity and acetylcholinecontent in animals were studied.The evalua-tion of memory deficits was based on the fol-lowing:(1)percentage of conditioned passiveavoidance reaction(CAR),(2)mean responsetime,(3)mean ability to perform correctly 5successive times in 10 trials,(4)mean numberof trials to correctly perform 9 out of 10 trials.It was found that AT_3 influences unconsolidatedmemory(three day training period)more thanconsolided memory(six day training period).It was also observed that the nmemonia effectsof AT_3 was associated with ECoG changes andcholinergic reduction in hippocampus.The majorfindings arising from studies of hippocampalelectrical activity in orienting experiments isthat hippocampal electrical response decreasedafter AT_3 injection.These findings suggestedthat the chronic administration of AT_3 raises thepossibility of impairing the ability of patients,particularly elderly ones,to learn new materialand to store,or acquire new information intolong-term memory