The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6

The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bizé, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh. OBJECTIVES: Late preconditioning reduces contractile dysfunction during myocardial stunning. Mechanisms involving adaptation of calcium handling during excitation-contraction coupling to late preconditioning remain to be established. Thus, we investigated whether the late preconditioned myocardium is associated with contractile adaptation and changes in the cardiac ryanodine receptor (RyR2) and its regulatory protein FKBP12.6. METHODS: Chronically instrumented conscious dogs (coronary occluder, ultrasonic crystals for sonomicrometry) underwent a 10-min coronary artery occlusion followed by reperfusion. They were studied 24 h later in the late preconditioned state (day 1). RESULTS: Maximal velocity of wall thickening at day 1 was increased as compared to corresponding baseline at day 0 (39+/-4 vs. 30+/-3 mm/s, p < 0.05) although systolic wall thickening was similar (2.8+/-0.2 vs. 2.9+/-0.2 mm), demonstrating a significant change in left ventricular inotropic state. Intracoronary infusion of ryanodine (0.5-6 microg) induced a dose-dependent decrease in wall thickening. In the late preconditioned state, this negative inotropic response was significantly reduced vs. control state, suggesting changes in sarcoplasmic reticulum (SR) Ca2+-release through RyR2. Immunoquantification of FKBP12.6 revealed a 2.8 fold ventricular increase after late preconditioning as compared to the control state. The amount of RyR2 and its phosphorylated state were similar and binding experiments did not reveal any alterations in B(max) or K(D) for RyR2. Calsequestrin, SERCA2a and phospholamban levels were not altered by late preconditioning. CONCLUSIONS: The late preconditioned myocardium is characterized by an adaptation of regional function associated with an increased expression of FKBP12.6. This demonstrates an adaptation of the SR Ca2+-release through RyR2 during late preconditioning.     

Discrepancies in Gleason scoring of prostate biopsies and radical prostatectomy specimens and the effects of multiple needle biopsies on scoring accuracy. A regional experience in Tamworth, Australia

BACKGROUND: The aim of this study was to review the discrepancies in Gleason scores (GS) of prostate biopsies and radical prostatectomy specimens and the effects of multiple-needle biopsies on scoring accuracy. METHODS: One hundred patients who had undergone consecutive radical prostatectomies (RP) between January 2004 and May 2006 were reviewed retrospectively. Patient information including age, prebiopsy prostate-specific antigen levels, biopsy GS, RP GS and pathology details were recorded and compared. RESULTS: The concordance rate of biopsy GS and RP GS was found to be at 43%, with 46% of biopsy specimens being undergraded. Eleven per cent of the specimens were overgraded. The accuracy was fairly similar when specimens were reported by the same or different pathologists, at 42 and 44%, respectively. The accuracy of biopsy GS improved with increasing number of biopsies taken. CONCLUSION: There are significant discrepancies in Gleason scoring of biopsy and RP specimens, with a concordance rate of 43% and undergrading rate of 46%. Increasing the number of biopsies helps improve scoring accuracy. Clinicians and patients need to be mindful when deciding cancer treatment options, in view of these discrepancies.     

Late reexposure after upper eyelid tarsoconjunctival flap for exposed porous orbital implant.

The records of four patients with exposed porous orbital implant treated with the upper eyelid tarsoconjunctival Hughes flap were reviewed. The tarsoconjunctival Hughes flap was fashioned for two patients with recurrent orbital porous implant exposure and two patients with primary orbital porous implant exposure (5 to 6 mm at largest dimension; mean, 5.6 mm). There were two hydroxyapatite and two high-density polyethylene implants. In all patients, reexposure (2 to 3 mm at largest dimension; mean, 2.5 mm) occurred 6 to 24 weeks (mean, 13 weeks) after the tarsoconjunctival Hughes flap procedure at the junction of the flap and the socket surface conjunctiva. Mean follow-up duration was 18.7 months (range, 7 to 27 months). Linear late reexposure is the main drawback of the upper eyelid tarsoconjunctival Hughes flap to cover an exposed orbital porous implant.     

Single-step transvaginal aspiration and drainage for suspected pelvic abscesses refractory to antibiotic therapy.

OBJECTIVE: For treatment of suspected pelvic abscesses, the use of the trocar technique avoids many of the technical challenges of the Seldinger method. The purpose of this study was to evaluate the effectiveness and safety of sonographically guided transvaginal aspiration or drainage with the trocar technique in suspected pelvic abscesses that were refractory to antibiotic treatment. METHODS: We retrospectively reviewed 22 patients with suspected pelvic abscesses refractory to antibiotic therapy who underwent single-step transvaginal pelvic aspiration or drainage between 1995 and 2000. RESULTS: Transvaginal aspiration or drainage was successful in 19 (86%) of the 22 patients. Of the 3 patients in whom aspiration or drainage failed, all ultimately went on to have surgery despite undergoing repeated drainage procedures. Drainage catheters were placed in 15 (68%) of the 22 patients and left in place an average of 3.7 days. Aspiration alone resulted in a 100% success rate, whereas drainage with catheter placement resulted in an 80% success rate. No complications, including bleeding, bowel perforation, and death, were reported in any of the procedures. CONCLUSIONS: Transvaginal ultrasonographically guided aspiration or catheter placement with the trocar technique is a safe and effective treatment for suspected pelvic abscesses refractory to antibiotic therapy.     

Detection of lymphocyte subsets using three-color/single-laser flow cytometry and the fluorescent dye Peridinin chlorophyll-a protein

The fluorescent dye, Peridinin chlorophyll A protein (PerCP) derived from dinoflagellate organisms (Glenodinium sp.) can be excited by a 488 nm laser and emits light with a large Stokes shift and no major spectral overlap with commonly used chromophores such as fluorescein isothiocyanate (FITC) and R-phycoerythrin (PE). PerCP was conjugated directly to various mouse monoclonal antibodies (mAb) specific for human leukocyte markers or to avidin for use with biotinylated-mAb, and used to perform three color single-laser flow cytometry. The efficacy of this method was demonstrated by analyzing the heterogeneity of thymus T lineage subsets and B lymphocyte subsets in blood. CD4–CD8–, CD4+CD8+ and CD4+CD8– or CD4–CD8+ subsets differ in their expression of cell-cell interaction markers including CD18, CD28, CD44 and Leu 8, and activation/subset markers CD45RO, CD45RA and CD26. Some CD5+ peripheral blood B cells, unlike CD5– B cells, expressed CD45RO or high levels of CD54 (ICAM-1) suggesting the CD5+ B cell population contains activated lymphocytes. The availability of such an accessible method for three color analysis will make it possible to do routine three color monitoring of immunologic diseases such as AIDS, and autoimmune or periodontal diseases.     

Validation of a short questionnaire in English and French for use in patients with persistent upper gastrointestinal symptoms despite proton pump inhibitor therapy: the PASS (Proton pump inhibitor Acid Suppression Symptom) test.

BACKGROUND: The management of persistent symptoms during acid suppression therapy in patients with gastroesophageal reflux disease or dyspepsia might be improved if patient-physician communication regarding the presence and character of these persistent symptoms were facilitated. AIM: To validate a short, simple questionnaire (the Proton pump inhibitor [PPI] Acid Suppression Symptom [PASS] test), in English and French, to identify patients with persistent acid-related symptoms during PPI therapy and document their response to a change in therapy. METHODS: Patients with persistent acid-related symptoms on PPI therapy were interviewed to produce a draft, five-item questionnaire; content validity was evaluated by focus groups comprising English- and French-speaking patients. Psychometric validity was subsequently evaluated in a multicentre, family practice-based study of English- and French-speaking patients with persistent acid-related upper gastrointestinal symptoms despite PPI therapy. The PASS test, Global Overall Symptom scale, Gastrointestinal Symptom Rating Scale (GSRS), Quality of Life in Reflux and Dyspepsia questionnaire and Reflux Disease Questionnaire were completed at baseline and repeated after one week while patients continued their original PPI therapy. All patients then received esomeprazole 40 mg once daily for four weeks, after which all questionnaires and an evaluation of overall treatment effect were completed. RESULTS: Content validity was established in 20 English- and 16 French-speaking patients. Psychometric validation in 158 English- and 113 French-speaking patients revealed good-to-excellent test-retest reliability coefficients: 0.76 for English; 0.68 for French. For construct validity, the PASS test showed moderate-to-high correlation with the GSRS scale (0.51 for English; 0.43 for French). After four weeks of therapy, the PASS test score fell to zero in 30% of English- and 33% of French-speaking patients, while the Global Overall Symptom score fell to one (no symptoms) in 32% of patients (English- and French-speaking); the PASS test demonstrated good responsiveness in comparison with the GSRS, Reflux Disease Questionnaire and Quality of Life in Reflux and Dyspepsia questionnaire. CONCLUSION: The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.     

Emerging HIV epidemics in muslim countries: Assessment of different cultural responses to harm reduction and implications for HIV control

Harm reduction, including needle exchange and opioid substitution therapy, has been demonstrated to reduce high-risk behavior and HIV infection among injection drug users. An increasing number of countries in the Middle East, North Africa, and Asia, including those with Muslim majorities, have experienced or are at risk for HIV epidemics initiated by burgeoning injection drug use. Although use of intoxicants is expressly forbidden within Islam, the local culture impacts the interpretation of Islamic law and influences the response to drug misuse, whether punitive or therapeutic. Harm reduction programming has received varying acceptance within this global region, which may be reflected by national trends in HIV prevalence. The purpose of this paper is to examine cultural and religious response to injecting drug use and associated HIV prevalence trends in Malaysia and Iran, with possible application of lessons learned to an emerging situation in Afghanistan.     

Selective oxidative stress in cell nuclei by nuclear-targeted D-amino acid oxidase

The effects of nuclear-localized oxidative stress on both nuclear antioxidant systems, and the processes that they regulate, are not clearly understood. Here, we targeted a hydrogen peroxide (H(2)O(2))-producing enzyme, D-amino acid oxidase (DAAO), to the nucleus (NLS-DAAO) and used this to generate H(2)O(2) in the nuclei of cells. On addition of N-acetyl-D-alanine (NADA), a substrate of DAAO, to NLS-DAAO-transfected HeLa cells, a twofold increase in ROS production relative to untreated, transfected control was observed. Staining of cellular thiols confirmed that NLS-DAAO-induced ROS selectively modified the nuclear thiol pool, whereas the cytoplasmic pool remained unchanged. Furthermore, NLS-DAAO/NADA-induced ROS caused significant oxidation of the nuclear GSH pool, as measured by nuclear protein S-glutathionylation (Pr-SSG), but under the same conditions, nuclear Trx1 redox state was not altered significantly. NF-kappaB reporter activity was diminished by NLS-DAAO/NADA-stimulated nuclear oxidation. We conclude that nuclear GSH is more susceptible to localized oxidation than is nuclear Trx1. Furthermore, the attenuation of NF-kappaB reporter activity in the absence of nuclear Trx1 oxidation suggests that critical nuclear redox proteins are subject to control by S-glutathionylation during oxidative stress in the nucleus.     

Molecular verification of transplacental transmission of Theileria lestoquardi in goat

Parasitology Research - Ovine and caprine malignant theileriosis (OCMT), a critical condition in small ruminant production, causes lethal infections. In September 2016, a total number of 400 goats...