The association of plasma C-reactive protein levels with anthropometric and lipid parameters in elderly Taiwanese

[[abstract]]C-reactive protein (CRP), a plasma inflammation marker, has been known to play a role in the development of cardiovascular diseases. This study aims to evaluate the association of CRP with anthropometric and plasma lipid parameters in elderly Taiwanese 65 years or older. Data from the Elderly Nutrition and Health Survey in Taiwan (1999-2000), a national probability sampling study conducted to gain an understanding of the dietary pattern, and nutritional and health status of elderly Taiwanese were analyzed. Results showed that in men, CRP was positively correlated with age and waist-to-hip ratio (WHR) (both p < 0.05) whereas in women, CRP was positively correlated with waist and WHR but negatively correlated with HDL-C (all p < 0.05). Linear regression analysis showed that log CRP was positively associated with WHR in both genders (p < 0.05) after adjusting for confounders. The correlation of CRP with WHR was stronger than that with both waist circumference and body mass index (BMI). Log CRP was inversely associated with HDL-C in women, but not men. The study suggests that among the anthropometric parameters examined, WHR is a stronger predictor for elevated CRP in elderly Taiwanese men and women. Whereas low HDL-C is a predictor among the plasma lipid parameters for elevated plasma CRP, at least in women. Gender differences exist in the association of CRP with anthropometric and lipid parameters

A novel hydroxyfuroic acid compound as an insulin receptor activator structure and activity relationship of a prenylindole moiety to insulin receptor activation

[[abstract]]Background: Diabetes Mellitus is a chronic disease and many patients of which require frequent subcutaneous insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far. Methods: A series of hydroxyfuroic acid compounds were synthesized and tested for their efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this study. Result and Conclusion: This study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potent as compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a moderate inhibitor to EGF receptor. Structure and activity relationship of the prenylindole moiety to insulin receptor activation is discussed

D-420720, A Novel Orally Active Sulfonamide Compound Dipeptidyl Peptidase IV Inhibitor: Structure and Activity Relationship of Arylsuffonamide to Dipeptidyl Peptidase IV Inhibition

[[abstract]]Diabetes mellitus is a chronic disease characteristic of poor glucose homeostasis that requires constant monitoring and adjustment of blood glucose levels by exogenous intervention. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are two incretin peptide hormones secreted from the intestine to synergize insulin's function at lowering blood glucose. The effects of GLP-1 or GIP administration are short-lived because they are rapidly inactivated by circulating dipeptidyl peptidase IV (DPP-IV). Therefore, DPP-IV inhibitors have been suggested to be a new class of molecule for treating hyperglycemic conditions in diabetic patients. The recent approval of Merck's Sitagliptin (a DPP-IV-specific inhibitor) indicates that DPP-IV inhibition is a good target for new therapeutic agent development. The present study was conducted to evaluate the efficacies of a series of dipeptidyl derivatives with a sulfonamide moiety as DPP-IV inhibitors. Among these compounds, D-420720 was a potent inhibitor (K-i = 39 nM), with a selectivity of 9160-fold over the DPP-II isozyme and elicits a hypoglycemic effect on oral glucose tolerance test with normal male ICR mice. Drug Dev Res 69:514-519,2008 (C) 2008 Wiley-Liss, Inc

COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer

Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer.An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted.The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas

Knocking down 10-formyltetrahydrofolate dehydrogenase increased oxidative stress and impeded zebrafish embryogenesis by obstructing morphogenetic movement

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Late capsular bag contraction and intraocular lens subluxation in retinitis pigmentosa: a case report

<p>Abstract</p> <p>Introduction</p> <p>Retinitis pigmentosa is clinically characterized by loss of predominantly rod photoreceptor function as well as loss of peripheral vision. The classic clinical triad is considered to be the presence of bone spicule pigmentation in the peripheral retina, arteriolar attenuation, and waxy disc pallor. Cataracts, most commonly of the posterior subcapsular type, are often found in all forms of retinitis pigmentosa. Ectopia lentis and lens dislocation are known risk factors for those with retinitis pigmentosa, presumably secondary to zonular fiber weakness and vitreous degeneration. The post-operative complication of lens dislocation following cataract extraction in patients with retinitis pigmentosa has also been documented.</p> <p>Case presentation</p> <p>We report a case of severe capsular bag contraction with intraocular lens subluxation following cataract extraction in a 58-year-old Hispanic woman with retinitis pigmentosa.</p> <p>Conclusion</p> <p>Patients with retinitis pigmentosa undergoing cataract surgery should be notified of this potentially late complication of surgery.</p

Influence of Sequence Changes and Environment on Intrinsically Disordered Proteins

Many large-scale studies on intrinsically disordered proteins are implicitly based on the structural models deposited in the Protein Data Bank. Yet, the static nature of deposited models supplies little insight into variation of protein structure and function under diverse cellular and environmental conditions. While the computational predictability of disordered regions provides practical evidence that disorder is an intrinsic property of proteins, the robustness of disordered regions to changes in sequence or environmental conditions has not been systematically studied. We analyzed intrinsically disordered regions in the same or similar proteins crystallized independently and studied their sensitivity to changes in protein sequence and parameters of crystallographic experiments. The observed changes in the existence, position, and length of disordered regions indicate that their appearance in X-ray structures dramatically depends on changes in amino acid sequence and peculiarities of the crystallographic experiment. Our study also raises general questions regarding protein evolution and the regulation of protein structure, dynamics, and function via variations in cellular and environmental conditions

Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

Assessing Internet addiction using the parsimonious Internet addiction components model - a preliminary study [forthcoming]

Internet usage has grown exponentially over the last decade. Research indicates that excessive Internet use can lead to symptoms associated with addiction. To date, assessment of potential Internet addiction has varied regarding populations studied and instruments used, making reliable prevalence estimations difficult. To overcome the present problems a preliminary study was conducted testing a parsimonious Internet addiction components model based on Griffiths’ addiction components (2005), including salience, mood modification, tolerance, withdrawal, conflict, and relapse. Two validated measures of Internet addiction were used (Compulsive Internet Use Scale [CIUS], Meerkerk et al., 2009, and Assessment for Internet and Computer Game Addiction Scale [AICA-S], Beutel et al., 2010) in two independent samples (ns = 3,105 and 2,257). The fit of the model was analysed using Confirmatory Factor Analysis. Results indicate that the Internet addiction components model fits the data in both samples well. The two sample/two instrument approach provides converging evidence concerning the degree to which the components model can organize the self-reported behavioural components of Internet addiction. Recommendations for future research include a more detailed assessment of tolerance as addiction component