The Lid Domain of Caenorhabditis elegans Hsc70 Influences ATP Turnover, Cofactor Binding and Protein Folding Activity

Hsc70 is a conserved ATP-dependent molecular chaperone, which utilizes the energy of ATP hydrolysis to alter the folding state of its client proteins. In contrast to the Hsc70 systems of bacteria, yeast and humans, the Hsc70 system of C. elegans (CeHsc70) has not been studied to date

In Silico Prediction and Analysis of Caenorhabditis EF-hand Containing Proteins

Calcium (Ca+2) is a ubiquitous messenger in eukaryotes including Caenorhabditis. Ca+2-mediated signalling processes are usually carried out through well characterized proteins like calmodulin (CaM) and other Ca+2 binding proteins (CaBP). These proteins interact with different targets and activate it by bringing conformational changes. Majority of the EF-hand proteins in Caenorhabditis contain Ca+2 binding motifs. Here, we have performed homology modelling of CaM-like proteins using the crystal structure of Drosophila melanogaster CaM as a template. Molecular docking was applied to explore the binding mechanism of CaM-like proteins and IQ1 motif which is a ∼25 residues and conform to the consensus sequence (I, L, V)QXXXRXXXX(R,K) to serve as a binding site for different EF hand proteins. We made an attempt to identify all the EF-hand (a helix-loop-helix structure characterized by a 12 residues loop sequence involved in metal coordination) containing proteins and their Ca+2 binding affinity in Caenorhabditis by analysing the complete genome sequence. Docking studies revealed that F165, F169, L29, E33, F44, L57, M61, M96, M97, M108, G65, V115, F93, N104, E144 of CaM-like protein is involved in the interaction with IQ1 motif. A maximum of 170 EF-hand proteins and 39 non-EF-hand proteins with Ca+2/metal binding motif were identified. Diverse proteins including enzyme, transcription, translation and large number of unknown proteins have one or more putative EF-hands. Phylogenetic analysis revealed seven major classes/groups that contain some families of proteins. Various domains that we identified in the EF-hand proteins (uncharacterized) would help in elucidating their functions. It is the first report of its kind where calcium binding loop sequences of EF-hand proteins were analyzed to decipher their calcium affinities. Variation in Ca+2-binding affinity of EF-hand CaBP could be further used to study the behaviour of these proteins. Our analyses postulated that Ca+2 is likely to be key player in Caenorhabditis cell signalling

The outcome of a long-term follow-up of pancreatic function after recovery from acute pancreatitis

Context: It is generally assumed that pancreatic function recovers completely after mild but not after severe acute pancreatitis. Objective :To evaluate both pancreatic function and quality of life in patients who had recovered from acute pancreatitis in a long-term follow-up study. Participants :Thirty-four patients (mean age: 56 years) who had recovered from biliary (n=26) or post ERCP (n=8) acute pancreatitis. The mean time after the event was 4.6 years. Main outcome measures :Pancreatic function was evaluated by fecal fat excretion, urinary 4-aminobenzoic acid (PABA) recovery, oral glucose tolerance test and pancreatic polypeptide (PP) secretion. In addition, the quality of life was measured by the gastrointestinal quality of life index (GIQLI). Results :Of the 34 patients, 22 (65%) had mild and 12 (35%) had severe acute pancreatitis. Exocrine insufficiency (fecal fat greater than 7 g/24h and/or urinary PABA recovery less than 50%) was present in 22 (65%) patients: in 10 (83%) after severe and in 12 (55%) after mild acute pancreatitis, respectively (P=0.140). Endocrine insufficiency was present in 12 patients (35%): 7 (32%) mild versus 5 (42%) severe acute pancreatitis; P=0.711. the quality of life was significantly impaired after acute pancreatitis, (P=0.024). No significant relationship was found between the severity of the pancreatitis and impairment of the quality of life (P=0.604). Conclusion :In a significant proportion of patients who had recovered from acute pancreatitis, exocrine and endocrine functional impairment was found. This finding is not confined only to patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered

Effect of fat digestion on superior mesenteric artery blood flow in humans

BACKGROUND AND AIM: Intraluminal nutrients stimulate superior mesenteric artery (SMA) blood flow. Of the macronutrients, especially fat affects the magnitude of the SMA blood flow response to a meal. Little is known however on the influence of fat hydrolysis on SMA flow. METHODS: We compared in eight healthy volunteers the SMA flow response (Doppler ultrasonography) to continuous intraduodenal fat perfusion (LCT, 240 kCal h(-1)) during conditions with normal hydrolysis (placebo, control), increased hydrolysis (pancreatic enzyme supplementation; 50 kU lipase) and impaired hydrolysis (orlistat 240 mg). RESULTS: Intraduodenal LCT significantly (P<0.01) increased SMA flow in all experiments over basal. The SMA flow response to fat during pancreatic enzyme supplementation (1.49 +/- 0.1 l min(-1)) was significantly (P<0.05) higher compared with placebo (1.11 +/- 0.16 l min(-1)). Lipase inhibition with orlistat did not significantly affect fat stimulated SMA flow compared with placebo: 0.89 +/- 0.08 l min(-1) versus 1.11 +/- 0.16 l min(-1). CONCLUSIONS: Administration of pancreatic enzymes significantly increases fat stimulated SMA flow. Fat digest products in the intestinal lumen contribute to the regulation of SMA blood flow

Efficacy of lower than standard doses of pancreatic enzyme supplementation therapy during acid inhibition in patients with pancreatic exocrine insufficiency

GOAL: To compare, during strong acid inhibition with omeprazole, the effect of 2 different doses of an enteric-coated pancreatic enzyme preparation on fecal fat excretion and abdominal symptoms in patients with exocrine insufficiency due to chronic pancreatitis (CP). BACKGROUND: Treatment with pancreatic enzymes reduces fecal fat excretion in patients with CP but is rather unsuccessful due to irreversible lipase inactivation at pH below 4. STUDY: Sixteen patients with CP (3 women, 13 men; age 53+/-3 y) participated in this randomized double blind 2-way cross over study. Fecal fat excretion and fat intake were measured and abdominal symptoms (visual analog scales) were scored during a 2 weeks control period, during omeprazole 60 mg+pancreatic enzymes 10,000 Federation Internationale Pharmaceutique IU lipase tid (treatment A) for 2 weeks and during omeprazole 60 mg+pancreatic enzymes, 20,000 Federation Internationale Pharmaceutique IU lipase tid (treatment B) for 2 weeks. RESULTS: During acid inhibition with enzyme supplementation fecal fat excretion was significantly (P<0.01) reduced compared with control: 18+/-7 and 18+/-5 g/24 h versus 36+/-8 g/24 h for treatment A, B, and control, respectively. Abdominal symptom score and general well being improved significantly (P<0.05) during treatments A and B versus control. No differences in fat excretion or symptoms scores between treatments A and B were observed. CONCLUSIONS: During strong acid inhibition, lower than recommended oral doses of pancreatic enzymes are therapeutically effective with respect to fat absorption and symptom reduction

Measuring satiety with pictures compared to visual analogue scales. An exploratory study.

Visual analogue scales (VAS) are a standard tool used to measure subjective appetite. To explore a potentially more intuitive and precise alternative, we developed a method based on pictures and assessed its performance characteristics vs. VAS. The objective was to compare the capacity of the two methods to discriminate appetite ratings between interventions. Both methods were applied within a previously published trial in which 16 healthy adults received standardised meals followed by three different ileal infusions in a balanced crossover design. At regular intervals volunteers indicated how many units of individually pictured food portions (for 10 different items) they would like to eat, and also scored six VAS. Methods were compared over different timeframes and assessed for their sensitivity to intervention effects. Pictures were more sensitive than VAS in differentiating intervention effects; however, further refinement and validation would be needed for pictures to become a standardised and accepted alternative to VAS for this type of research

Tako-tsubo cardiomyopathy is age-dependent in men, but not in women

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Multimodality Imaging Assessment of Prosthetic Heart Valves

Echocardiography and fluoroscopy are the main techniques for prosthetic heart valve (PHV) evaluation, but because of specific limitations they may not identify the morphological substrate or the extent of PHV pathology. Cardiac computed tomography (CT) and magnetic resonance imaging (MRI) have emerged as new potential imaging modalities for valve prostheses. We present an overview of the possibilities and pitfalls of CT and MRI for PHV assessment based on a systematic literature review of all experimental and patient studies. For this, a comprehensive systematic search was performed in PubMed and Embase on March 24, 2015, containing CT/MRI and PHV synonyms. Our final selection yielded 82 articles on surgical valves. CT allowed adequate assessment of most modern PHVs and complemented echocardiography in detecting the obstruction cause (pannus or thrombus), bioprosthesis calcifications, and endocarditis extent (valve dehiscence and pseudoaneurysms). No clear advantage over echocardiography was found for the detection of vegetations or periprosthetic regurgitation. Whereas MRI metal artifacts may preclude direct prosthesis analysis, MRI provided information on PHV-related flow patterns and velocities. MRI demonstrated abnormal asymmetrical flow patterns in PHV obstruction and allowed prosthetic regurgitation assessment. Hence, CT shows great clinical relevance as a complementary imaging tool for the diagnostic work-up of patients with suspected PHV obstruction and endocarditis. MRI shows potential for functional PHV assessment although more studies are required to provide diagnostic reference values to allow discrimination of normal from pathological conditions