Partial redirection of transgenic human growth hormone secretion from rat salivary glands

Regulated secretory pathway proteins, when delivered as transgenes to salivary glands, are secreted predominantly into saliva. This is not useful for those proteins whose therapeutic function is required systemically, for example, human growth hormone (hGH). One strategy to improve the efficiency of hGH secretion into the bloodstream involves manipulation of existing sorting signals. The C terminus of hGH is highly conserved and contains a domain similar to the regulated pathway sorting domain of pro-opiomelanocortin (POMC). We hypothesized that, similar to POMC, mutation of this domain would divert hGH secretion from the regulated to the constitutive pathway, which in salivary glands leads to the bloodstream. Several mutations were made in the C terminus of the hGH cDNA and tested in vitro. One biologically active mutant containing E174A and E186A substitutions, and with an included C-terminal extension, was studied in greater detail. Compared with wild-type hGH, we found that this mutant hGH accumulated in the Golgi/trans-Golgi network and showed increased basal secretion in AtT20 cells, a model endocrine cell line. Importantly, in vivo, the mutant hGH displayed a relative increase in the proportion of constitutive pathway secretion seen from rat salivary glands, with a significantly lower saliva-versus-serum secretion ratio (p=0.03). Although this mutant is unlikely to be therapeutically beneficial, these results suggest that the final destination of a transgenic secretory protein may be controlled by reengineering its sorting determinants.     

A randomised controlled trial comparing completeness of responses of three methods of collecting patient-reported outcome measures in men diagnosed with prostate cancer

Quality of Life Research - The purpose of the study was to compare completeness, timeliness and cost of patient-reported outcome measures (PROMs) collection using telephone, email and post in men...     

Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9

Nonalcoholic steatohepatitis (NASH) is the most common liver disease in industrialized countries. NASH is a progressive disease that can lead to cirrhosis, cancer, and death, and there are currently no approved therapies. The development of NASH in animal models requires intact TLR9, but how the TLR9 pathway is activated in NASH is not clear. Our objectives in this study were to identify NASH-associated ligands for TLR9, establish the cellular requirement for TLR9, and evaluate the role of obesity-induced changes in TLR9 pathway activation. We demonstrated that plasma from mice and patients with NASH contains high levels of mitochondrial DNA (mtDNA) and intact mitochondria and has the ability to activate TLR9. Most of the plasma mtDNA was contained in microparticles (MPs) of hepatocyte origin, and removal of these MPs from plasma resulted in a substantial decrease in TLR9 activation capacity. In mice, NASH development in response to a high-fat diet required TLR9 on lysozyme-expressing cells, and a clinically applicable TLR9 antagonist blocked the development of NASH when given prophylactically and therapeutically. These data demonstrate that activation of the TLR9 pathway provides a link between the key metabolic and inflammatory phenotypes in NASH.     

Glucocorticoids are not always deleterious for bone

A 23‐year‐old man with the rare sclerosing bone disorder van Buchem disease presented with progressively worsening headaches that eventually became persistent and associated with papilledema. Increased intracranial pressure was diagnosed, and the patient had a ventriculoperitoneal drain inserted as well as simultaneously receiving treatment with prednisone. Before starting treatment, there was biochemical evidence for increased bone turnover and for steady increases in bone mineral density (BMD) at the spine and total hip despite the patient having reached his peak height of 197 cm at the age of 19 years. Treatment with prednisone for 2 years resulted in biochemical and histologic suppression of bone formation as well as of bone resorption and arrest of further bone accumulation. Our data suggest that glucocorticoids (GCs) may represent an attractive alternative to the high‐risk surgical approaches used in the management of patients with progressive sclerosing bone disorders. Our findings also suggest that whereas sclerostin may not be required for the action of GCs on bone formation, it may well be important for the action of GCs on bone resorption. The exact mechanism by which sclerostin may be involved in the regulation of bone resorption is as yet to be explored. © 2010 American Society for Bone and Mineral Research.     

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Introduction and Hypothesis  

The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle.     

Non-culture diagnosis of Chlamydia trachomatis genital infection in sexually active women

Infections caused by Chlamydia trachomatis (CT) are one of the most prevalent of all sexually transmitted diseases (STD). This cross sectional study was carried out to diagnose genital CT infection on 108 (59 pregnant and 49 non-pregnant) women attending at Department of Gynaecology and Obstetrics, Mymensingh Medical College Hospital (MMCH) during the period from January 2009 to December 2009. This non- culture technique was based on detection of CT major outer membrane protein (MOMP) by Direct Fluorescence Antibody Test (DFAT) from endocervical swab. Chlamydial inclusion bodies (IB) were looked for using Iodine stain. CT antigens were detected in 45.3% (49/108) cases by DFAT; IBs were detected in 5.5% cases (06/108) by Iodine staining technique. Majority of CT positive cases (65%) were found in the younger age group (15 to 25 years). The CT infection was found 47.2 % (35/74) in symptomatic cases, 41.1% (14/34) in asymptomatic cases and 47.4% in pregnant group, 42.8% in non-pregnant group. Although high incidence of genital chlamydia infection is common both in pregnant, non-pregnant, symptomatic and asymptomatic women in Bangladesh an early and reliable diagnostic method for genital chlamydia infection in Bangladesh should be further explored.     

Breastfeeding and cognitive development of children: assessment at one year of age

Breastfeeding is the fundamental component of child survival strategy. It significantly influences neurological development of children. The study was conducted to assess whether exclusive and prolonged breastfeeding improves children's cognitive development, including low birth weight (LBW) babies, in a developing country setting like Bangladesh. This observational study was done on a cohort of newborn infants who were discharged from the special care baby unit of Dhaka Shishu Hospital during January 2006 to December 2008 with proper counseling about exclusive and prolonged breastfeeding. Their neuro-developmental follow-up was started at 4 weeks postnatal age and continued at 3-monthly intervals up to 1 year of age. At each visit, cognitive development was assessed using the Bayley Scales of Infant Development (BSID II). Cognitive development was compared between the babies of exclusive vs. non exclusive breastfeeding, normal weight vs. low birth weight and male vs. female babies. A total of 105 cases were successfully followed-up during this period. Out of these 47(44.8%) babies were exclusively breastfed up to 6 month of age and 58(55.2%) were in nonexclusive group. Overall Psychomotor Development Index (PDI) was slightly more (108.40 ± 23.06 vs. 103.23 ± 19.87) in the exclusive breast fed babies in comparison to nonexclusive breast fed babies, but was significantly more in babies having birth weight >2.5 kg in comparison to those having birth weight of <2.5 kg. Other parameters of cognitive development were more or less same in both normal and LBW groups. Mental and motor development was same in both boys and girls. In behavior ratings, cooperation was significantly high (5.89 ± 2.54 vs. 4.71 ± 3.13, p=0.05) and vocalization (5.89 ± 1.07 vs. 4.58 ± 1.16) was also high, though not significant, in girls than boys.     

Cardiovascular complications of chronic renal failure - an updated review

Chronic kidney disease (CKD) is a worldwide public health problem. Cardiovascular disease (CVD) is frequently associated with CKD, which is important because individuals with CKD are more likely to die from CVD than to develop kidney failure. CVD in CKD is treatable and potentially preventable and CKD appears to be a risk factor for CVD. In order of incidence and frequency systemic hypertension, left ventricular failure, congestive cardiac failure, ischemic heart disease, anaemic heart failure, rhythm disturbances, pericarditis with or without effusion, cardiac tamponade, uraemic cardiomyopathy are various cardiovascular complications encountered in patients with chronic renal failure. A patient may present with one or more complications of cardiovascular system. The survival rate and prognosis to a great extent depends on proper management of these complications. Use of regular dialysis and renal transplant has changed the death pattern in developed countries but it is still a major problem in developing country. The aim of this article is early detection of CKD and proper management of it thereby preventing the major cardiovascular complications.     

阿司匹林与结直肠癌存活率的关系

背景及目的：随机对照临床试验已经表明阿司匹林可降低结直肠癌的发生风险,动物实验还发现其可抑制肿瘤生长与转移,但阿司匹林与已确诊结直肠癌患者存活率的关系仍不可知.本研究探讨了在已确诊的结直肠癌患者中,阿司匹林与结直肠癌总体存活率的关系.     

聚乙二醇干扰素α（-2b或α-2a与利巴韦林联合治疗丙型肝炎疗效比较

背景及目的：随机对照临床试验已经表明阿司匹林可降低结直肠癌的发生风险,动物实验还发现其可抑制肿瘤生长与转移,但阿司匹林与已确诊结直肠癌患者存活率的关系仍不可知.本研究探讨了在已确诊的结直肠癌患者中,阿司匹林与结直肠癌总体存活率的关系.