Bile-pancreatic juice exclusion promotes Akt/NF-kB activation and chemokine production in ligation-induced acute pancreatitis

Using a unique surgical model (the donor rat model), we showed previously that duodenal replacement of bile-pancreatic juice, obtained fresh from a donor rat, ameliorates ligation-induced acute pancreatitis. We hypothesize that bile-pancreatic juice exclusion from gut exacerbates Akt/nuclear factor-kB (NF-kB) pathway activation and induces chemokine production in ligation-induced acute pancreatitis. We compared rats with bile-pancreatic duct ligation to those with duodenal bile-pancreatic juice replacement fresh from a donor rat beginning immediately before duct ligation. Sham control rats had ducts dissected but not ligated. Rats were killed 1 or 3 hours after operation (n=7/group). Akt activation (immunoblotting, immune-complex kinase assay, and ELISA), inhibitory protein I-kB (I-kB) activation (immunoblotting), and production of chemokines MCP-1 and RANTES (ELISA) were measured in pancreatic homogenates. NF-kB was quantitated in nuclear fractions using electrophoretic mobility shift assay. Duct ligation produced significant increases in pancreatic Akt, IkB, and NF-kB activation and production of MCP-1 and RANTES. Activation of the Akt/NF-kB pathway and increased MCP-1 and RANTES production in response to duct ligation were significantly reduced by bile-pancreatic juice replacement (ANOVA, P<0.05). Bile-pancreatic juice exclusion stimulates Akt/NF-kB pathway activation and increases chemokine production in ligation-induced acute pancreatitis. Presented at the annual meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 16, 2005 (poster).     

Spondyloarthritis in North Africa: an update

Clinical Rheumatology - Spondyloarthritis (SpA) has been less well studied than rheumatoid arthritis in North Africa, due to a belief that it is rare and benign in certain populations. The main...     

<Emphasis Type="Italic">PTEN</Emphasis>-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients

Purpose  

The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established.     

Diminished degradation of myelin basic protein by anti-sulfatide antibody and interferon-gamma in myelin from glia maturation factor-deficient mice

In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-alpha and IFN-gamma in inducing myelin basic protein (MBP) degradation in myelin isolated from control wild type (WT) and glia maturation factor (GMF)-deficient (GMF-KO) mice. GMF was not detected in isolated myelin from WT and GMF-KO mice although it is present in brains of WT mice. Our results show that calcium-dependent neutral protease activity caused significantly elevated degradation of 18.5 and/or 17.5kDa isoforms of MBP in WT myelin treated with RmAb or IFN-gamma. In contrast, MBP degradation in isolated myelin from GMF-KO mice remained unaffected following treatment with RmAb, IFN-gamma, or GM-CSF. Neither the 14kDa isoform of MBP nor proteolipid protein (PLP) showed an elevated degradation compared to controls. A virtual absence of GM-CSF, TNF-alpha and IFN-gamma in GMF-KO brain compared to WT was also evident when the animals were challenged with MOG 35-55. Additionally, the myelin from GMF-KO mice showed difference in distribution of myelin oligodendrocyte glycoprotein (MOG) and beta-tubulin in a sucrose density gradient myelin-axolemmal fractions compared to WT. Taken together, our data suggests a role for GMF in the biochemical organization of myelin and thereby its effect on MBP degradation induced by RmAb and IFN-gamma.     

The spectrum of psoriatic arthritis in a South African cohort

The aim of this study was to describe the clinical features of patients with psoriatic arthritis (PsA) in a South African cohort. This is a retrospective analysis of patients contributing to development of the international classification criteria for PsA, ClASsification criteria for Psoriatic ARthritis (CASPAR). Patients were all seen at the arthritis clinics at Groote Schuur Hospital, Cape Town. Demographic, clinical, laboratory and radiographic information was collected. This study describes the relevant findings relating to the clinical profile of the patients seen at our centre as well as the effect of family history and/or dactylitis in determining the severity of psoriatic arthritis. There were 45 patients with a male to female ratio of 1:1.25. The mean age of psoriasis onset was 38.34 years (SD 15.54), whilst that of arthritis onset was 43.86 years (SD 13.4). Polyarthritis was the commonest pattern and sacro-iliitis was uncommon. Dactylitis was present in 26%. The presence of family history or of dactylitis did not predict more severe disease. There was a significant correlation between tender and swollen joints. The mean Health Assessment Questionnaire (HAQ) score was 1.05. Eighty-three percent showed evidence of radiological changes, and distal interphalangeal (DIP) erosions were found in 54%. Arthritis mutilans was present in 31%. There were no black subjects in the cohort. The clinical patterns of PsA in our cohort are similar to those reported elsewhere. The paucity of blacks amongst this cohort requires further study. PsA-specific measures of disease activity need to be developed. PsA causes significant joint damage and disability.     

Is skeletonised internal mammary harvest better than pedicled internal mammary harvest for patients undergoing coronary artery bypass grafting?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether skeletonised internal mammary artery (IMA) is better than pedicle IMA in coronary artery bypass grafting? Altogether 106 papers were found using the reported search, of which 12 presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that skeletonisation increases the length of conduit by around 3 cm and may also increase flow and conduit diameter. Skeletonisation should be the technique of choice for diabetics in whom BIMA harvest is desired, but at the expense of an extra 15-20 min per operation, no convincing outcome benefits have been shown for single IMA harvest.     

Good outcome and valve function despite medtronic‐corevalve underexpansion

An 80‐year old nun with severe calcific aortic stenosis and a bicuspid aortic valve was referred for transcatheter aortic valve implantation. She was declined for conventional surgery on the basis of poor left ventricular function, frailty, and a logistic EuroSCORE of 29.66. A 29‐mm Medtronic‐Corevalve bioprosthesis was implanted by transfemoral route. The inflow portion of the stent frame was grossly underexpanded. However, aortic valve area at 1.3 cm² was more than satisfactory for a body surface area of 1.29 m² (indexed area 1.0 cm²/m², peak gradient 23, and mean 16 mmHg). There was an early sustained improvement in New York Heart Association (NYHA) status, and there was no change in valvular function at 2 year follow‐up. This case highlights that gross underexpansion of the Medtronic‐Corevalve stent frame is compatible with good bioprosthetic function and excellent symptomatic recovery. © 2010 Wiley‐Liss, Inc.     

Receded near point of convergence as a predictor of mild cognitive impairment in the general geriatric population: results from a population-based study

AIM: To investigate the relationship between near point of convergence (NPC) and mild cognitive impairment (MCI) in the general elderly population. METHODS: The present report is a part of the Tehran Geriatric Eye Study (TGES): a population-based cross-sectional study conducted on individuals 60 years of age and above living in Tehran, Iran using the multi-stage stratified random cluster sampling method. Cognitive status was assessed using the Persian version of the Mini-Mental State Examination (MMSE). All study participants underwent complete ocular examination including measurement of uncorrected and best-corrected visual acuity, objective and subjective refraction, cover testing, NPC measurement, and slit-lamp biomicroscopy. RESULTS: The data of 1190 individuals were analyzed for this report. The mean age of the participants analyzed was 66.82±5.42 (60-92y) and 728 (61.2%) of them were female. Patients with MCI had a significantly more receded NPC compared to subjects with normal cognitive status (10.89±3.58 vs 7.76±2.71 cm, P<0.001). In the multivariable logistic regression model and in the presence of confounding variables, a receded NPC was statistically significantly associated with an increased risk of MCI (odds ratio: 1.334, 95% confidence interval: 1.263 to 1.410, P<0.001). According to receiver operating characteristic (ROC) analysis, a cut point NPC> 8.5 cm (area under the curve: 0.764, P<0.001) could predict the presence of MCI with a sensitivity and specificity of 70.9% and 69.5%, respectively. CONCLUSION: A receded NPC can be clinically proposed as a predictor of MCI in older adults. It is recommended that elderly with a receded NPC>8.50 cm undergo detailed cognitive screening for a definite diagnosis of MCI. In this case, the necessary interventions can be carried out to slow down MCI progression to dementia.