bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuation of endoplasmic reticulum stress and mitochondrial injury in kidney with ischemic postconditioning application and trimetazidine treatment
Authors: Mahfoudh-Boussaid Asma , Zaouali Mohamed Amine , Hauet Thierry , Hadj-Ayed Kaouther , Miled Abdel-Hédi , Ghoul-Mazgar Sonia , Saidane-Mosbahi Dalila , Rosello-Catafau Joan , Abdennebi Hassen Ben 
Published: August 2012

Abstract

Background
Endoplasmic reticulum (ER) and mitochondria have been implicated in the pathology of renal ischemia/reperfusion (I/R). In the present study, we investigated whether the use of ischemic postconditioning (IPostC) and trimetazidine (TMZ) separately or combined could reduce ER stress and mitochondria damage after renal ischemia.

Methods
Kidneys of Wistar rats were subjected to 60-min of warm ischemia followed by 120-min of reperfusion (I/R group, n = 6), or to 6 cycles of ischemia/reperfusion (10-s each cycle) just after 60-min of warm ischemia (IPostC group, n = 6), or to i.p. injection of TMZ (3 mg/kg) 30-min before ischemia (TMZ group, n = 6), or to the combination of both treatments (IPostC+TMZ group, n = 6). The results of these experimental groups were compared to those of a sham-operated group in which rat renal pedicles were only dissected. Sodium reabsorption rate, creatinine clearance lactate deshydrogenase (LDH) activity in plasma, and concentration of malonedialdehyde (MDA) in tissue were determined. In addition, Western blot analysis was performed to identify the amounts of cytochrome c, c-JunNH2-terminal kinase (JNK), voltage-dependent anion channel (VDAC), glycogen synthase kinase 3-beta (GSK3-β), and ER stress parameters.

Results
IPostC or/and TMZ significantly decreased cytolysis, oxidative stress and improved renal function in comparison to I/R group. IPostC but not TMZ significantly attenuated ER stress parameters versus I/R group. Indeed, it down-regulated the glucose-regulated protein 78 (GRP78), the activating transcription factor 4 (ATF4), the RNA activated protein kinase (PKR)-like ER kinas (PERK), the X box binding protein-1 (XBP-1) and the caspase12 protein levels. TMZ treatment significantly augmented GSK3-β phosphorylation and reduced levels of cytochrome c and VDAC phosphorylation in comparison to IPostC application. The combination of both treatments gave a synergetic effect. It significantly improved the survival rate, attenuated cytolysis, oxidative stress and improved renal function.

Conclusion
This study revealed that IPostC protects kidney from I/R injury by suppressing ER stress while the beneficial effects of TMZ are mediated by mitochondria protection. The combination of both treatments ameliorated functional recovery.
Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak
Authors: Corogeanu Diana , Willmes Ruben , Wolke Martina , Plum Georg , Utermöhlen Olaf , Krönke Martin 
Published: August 2012

Abstract

Background
The shiga toxin-producing E. coli (STEC) O104:H4 caused a major outbreak in Germany in spring 2011. STEC are usually susceptible to common antibiotics. However, antibiotic treatment of STEC-infected patients is not recommended because STEC may enhance production and release of shiga toxins (STX) in response to antibiotics, which eventually enhances the frequency and severity of clinical symptoms, including haemolytic uraemic syndrome (HUS) and fatalities.

Results
We characterized the response to antibiotics of STEC O104:H4 isolates from two HUS patients during the German STEC outbreak in spring 2011 in comparison to the common STEC O157:H7. Liquid cultures of STEC O157:H7 and O104:H4 were incubated with graded dilutions of the antibiotics ciprofloxacin, meropenem, fosfomycin, gentamicin, rifampicin, and chloramphenicol. At defined times of antibiotic treatment, transcriptional activation of the STX2 gene, contents of STX and STX-activity in the culture supernatants were quantified. Unlike the common serotype O157:H7, STEC O104:H4 does not release STX in response to therapeutic concentrations of ciprofloxacin, meropenem, fosfomycin, and chloramphenicol.

Conclusions
In future outbreaks, the response of the respective epidemiologic STEC strain to antibiotics should be rapidly characterized in order to identify antibiotics that do not enhance the release of STX. This will eventually allow clinical studies tackling the question whether antibiotic treatment impacts on the eradication of STEC, clinical course of disease, and frequency of carriers.
Peri-operative chemotherapy in the management of resectable colorectal cancer pulmonary metastases
Authors: Hawkes Eliza A , Ladas George , Cunningham David , Nicholson Andrew G , Wassilew Katharina , Barbachano Yolanda , Ratnayake Gihan , Rao Sheela , Chau Ian 
Published: August 2012

Abstract

Background
Surgery is often advocated in patients with resectable pulmonary metastases from colorectal cancer (CRC). Our study aims to evaluate peri-operative chemotherapy in patients with metastastic CRC undergoing pulmonary metastasectomy.

Methods
Patients treated for CRC who underwent pulmonary metastasectomy by a single surgeon were identified. Outcome measures included survival, peri-operative complications, radiological and histological evidence of chemotherapy-induced lung toxicities.

Results
Between 1997 and 2009, 51 eligible patients were identified undergoing a total of 72 pulmonary resections. Thirty-eight patients received peri-operative chemotherapy, of whom 9 received an additional biological agent. Five-year overall survival rate was 72% in the whole cohort - 74% and 68% in those who received peri-operative chemotherapy (CS) and those who underwent surgery alone (S) respectively. Five-year relapse free survival rate was 31% in the whole cohort - 38% and ≤18% in CS and S groups respectively. Only 8% had disease progression during neoadjuvant chemotherapy. There were no post-operative deaths. Surgical complications occurred in only 4% of patients who received pre-operative chemotherapy. There was neither radiological nor histological evidence of lung toxicity in resected surgical specimens.

Conclusions
Peri-operative chemotherapy can be safely delivered to CRC patients undergoing pulmonary metastasectomy. Survival in this selected group of patients was favourable.
Understanding how adherence goals promote adherence behaviours: a repeated measure observational study with HIV seropositive patients
Authors: Jones Gareth , Hawkins Kim , Mullin Rebecca , Nepusz Tamás , Naughton Declan P , Sheeran Paschal , Petróczi Andrea 
Published: August 2012

Abstract

Background
The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95%) of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80%) of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investigate a wide range of psychological and personality factors that may lead to adherence/non-adherence to medical treatment and exercise programmes.

Methods
HIV positive patients who are referred to the physiotherapist-led 10-week exercise programme as part of the standard care are continuously recruited. Data on social cognitive variables (attitude, intention, subjective norms, self-efficacy, and outcome beliefs) about the goal and specific behaviours, selected personality factors, perceived quality of life, physical activity, self-reported adherence and physical assessment are collected at baseline, at the end of the exercise programme and again 3 months later. The project incorporates objective measures of both exercise (attendance log and improvement in physical measures such as improved fitness level, weight loss, improved circumferential anthropometric measures) and medication adherence (verified by non-invasive hair analysis).

Discussion
The novelty of this project comes from two key aspects, complemented with objective information on exercise and medication adherence. The project assesses beliefs about both the underlying goal such as following prescribed treatment; and about the specific behaviours such as undertaking the exercise or taking the medication, using both implicit and explicit assessments of patients’ beliefs and attitudes. We predict that i) the way people think about the underlying goal of their treatments explains medication and exercise behaviours over and above the effects of the behaviour-specific thinking and ii) the relationship between adherence to exercise and to medical treatment is stronger among those with more favourable views about the goal. Results from this study should identify the key contributing factors to inform subsequent adherence research and afford a more streamlined assessment matrix. The project also aims to inform patient care practices.

UK Clinical Research Network registration number
UKCRN 7842.
Angiotensin-converting enzyme inhibition and food restriction in diabetic mice do not correct the increased sensitivity for ischemia-reperfusion injury
Authors: Van der Mieren Gerry , Nevelsteen Ines , Vanderper Annelies , Oosterlinck Wouter , Flameng Willem , Herijgers Paul 
Published: August 2012

Abstract

Background
The number of patients with diabetes or the metabolic syndrome reaches epidemic proportions. On top of their diabetic cardiomyopathy, these patients experience frequent and severe cardiac ischemia-reperfusion (IR) insults, which further aggravate their degree of heart failure. Food restriction and angiotensin-converting enzyme inhibition (ACE-I) are standard therapies in these patients but the effects on cardiac IR injury have never been investigated. In this study, we tested the hypothesis that 1° food restriction and 2° ACE-I reduce infarct size and preserve cardiac contractility after IR injury in mouse models of diabetes and the metabolic syndrome.

Methods
C57Bl6/J wild type (WT) mice, leptin deficient ob/ob (model for type II diabetes) and double knock-out (LDLR-/-;ob/ob, further called DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome) were used. The effects of 12 weeks food restriction or ACE-I on infarct size and load-independent left ventricular contractility after 30 min regional cardiac ischemia were investigated. Differences between groups were analyzed for statistical significance by Student’s t-test or factorial ANOVA followed by a Fisher’s LSD post hoc test.

Results
Infarct size was larger in ob/ob and DKO versus WT. Twelve weeks of ACE-I improved pre-ischemic left ventricular contractility in ob/ob and DKO. Twelve weeks of food restriction, with a weight reduction of 35-40%, or ACE-I did not reduce the effect of IR.

Conclusion
ACE-I and food restriction do not correct the increased sensitivity for cardiac IR-injury in mouse models of type II diabetes and the metabolic syndrome.
Regulation of Toll-like receptor 4-mediated immune responses through Pasteurella multocida toxin-induced G protein signalling
Authors: Hildebrand Dagmar , Sahr Aline , Wölfle Sabine J , Heeg Klaus , Kubatzky Katharina F 
Published: August 2012

AbstractBackgroundLipopolysaccharide (LPS)-triggered Toll-like receptor (TLR) 4-signalling belongs to the key innate defence mechanisms upon infection with Gram-negative bacteria and triggers the subsequent activation of adaptive immunity. There is an active crosstalk between TLR4-mediated and other signalling cascades to secure an effective immune response, but also to prevent excessive inflammation. Many pathogens induce signalling cascades via secreted factors that interfere with TLR signalling to modify and presumably escape the host response. In this context heterotrimeric G proteins and their coupled receptors have been recognized as major cellular targets. Toxigenic strains of Gram-negativePasteurella multocidaproduce a toxin (PMT) that constitutively activates the heterotrimeric G proteins Gαq, Gα13and Gαiindependently of G protein-coupled receptors through deamidation. PMT is known to induce signalling events involved in cell proliferation, cell survival and cytoskeleton rearrangement.ResultsHere we show that the activation of heterotrimeric G proteins through PMT suppresses LPS-stimulated IL-12p40 production and eventually impairs the T cell-activating ability of LPS-treated monocytes. This inhibition of TLR4-induced IL-12p40 expression is mediated by Gαi-triggered signalling as well as by Gβγ-dependent activation of PI3kinase and JNK.Taken together we propose the following model: LPS stimulates TLR4-mediated activation of the NFĸB-pathway and thereby the production of TNF-α, IL-6 and IL-12p40. PMT inhibits the production of IL-12p40 by Gαi-mediated inhibition of adenylate cyclase and cAMP accumulation and by Gβγ-mediated activation of PI3kinase and JNK activation.ConclusionsOn the basis of the experiments with PMT this study gives an example of a pathogen-induced interaction between G protein-mediated and TLR4-triggered signalling and illustrates how a bacterial toxin is able to interfere with the host’s immune response.
Nicotine patches and quitline counseling to help hospitalized smokers stay quit: study protocol for a randomized controlled trial
Authors: Cummins Sharon , Zhu Shu-Hong , Gamst Anthony , Kirby Carrie , Brandstein Kendra , Klonoff-Cohen Hillary , Chaplin Edward , Morris Timothy , Seymann Gregory , Lee Joshua 
Published: August 2012

Abstract

Background
Hospitalized smokers often quit smoking, voluntarily or involuntarily; most relapse soon after discharge. Extended follow-up counseling can help prevent relapse. However, it is difficult for hospitals to provide follow-up and smokers rarely leave the hospital with quitting aids (for example, nicotine patches). This study aims to test a practical model in which hospitals work with a state cessation quitline. Hospital staff briefly intervene with smokers at bedside and refer them to the quitline. Depending on assigned condition, smokers may receive nicotine patches at discharge or extended quitline telephone counseling post-discharge. This project establishes a practical model that lends itself to broader dissemination, while testing the effectiveness of the interventions in a rigorous randomized trial.

Methods/design
This randomized clinical trial (N = 1,640) tests the effect of two interventions on long-term quit rates of hospitalized smokers in a 2 x 2 factorial design. The interventions are (1) nicotine patches (eight-week, step down program) dispensed at discharge and (2) proactive telephone counseling provided by the state quitline after discharge. Subjects are randomly assigned into: usual care, nicotine patches, telephone counseling, or both patches and counseling. It is hypothesized that patches and counseling have independent effects and their combined effect is greater than either alone. The primary outcome measure is thirty-day abstinence at six months; a secondary outcome is biochemically validated smoking status. Cost-effectiveness analysis is conducted to compare each intervention condition (patch alone, counseling alone, and combined interventions) against the usual care condition. Further, this study examines whether smokers’ medical diagnosis is a moderator of treatment effect. Generalized linear (binomial) mixed models will be used to study the effect of treatment on abstinence rates. Clustering is accounted for with hospital-specific random effects.

Discussion
If this model is effective, quitlines across the U.S. could work with interested hospitals to set up similar systems. Hospital accreditation standards related to tobacco cessation performance measures require follow-up after discharge and provide additional incentive for hospitals to work with quitlines. The ubiquity of quitlines, combined with the consistency of quitline counseling delivery as centralized state operations, make this partnership attractive.

Trial registration
Smoking cessation in hospitalized smokers NCT01289275. Date of registration February 1, 2011; date of first patient August 3, 2011.
Early prediction of histopathological response of rectal tumors after one week of preoperative radiochemotherapy using 18 F-FDG PET-CT imaging. A prospective clinical study
Authors: Goldberg Natalia , Kundel Yulia , Purim Ofer , Bernstine Hanna , Gordon Noa , Morgenstern Sara , Idelevich Efraim , Wasserberg Nir , Sulkes Aaron , Groshar David , Brenner Baruch 
Published: August 2012

Abstract

Background
Preoperative radiochemotherapy (RCT) is standard in locally advanced rectal cancer (LARC). Initial data suggest that the tumor’s metabolic response, i.e. reduction of its 18 F-FDG uptake compared with the baseline, observed after two weeks of RCT, may correlate with histopathological response. This prospective study evaluated the ability of a very early metabolic response, seen after only one week of RCT, to predict the histopathological response to treatment.

Methods
Twenty patients with LARC who received standard RCT regimen followed by radical surgery participated in this study. Maximum standardized uptake value (SUV-MAX), measured by PET-CT imaging at baseline and on day 8 of RCT, and the changes in FDG uptake (ΔSUV-MAX), were compared with the histopathological response at surgery. Response was classified by tumor regression grade (TRG) and by achievement of pathological complete response (pCR).

Results
Absolute SUV-MAX values at both time points did not correlate with histopathological response. However, patients with pCR had a larger drop in SUV-MAX after one week of RCT (median: -35.31% vs −18.42%, p = 0.046). In contrast, TRG did not correlate with ΔSUV-MAX. The changes in FGD-uptake predicted accurately the achievement of pCR: only patients with a decrease of more than 32% in SUV-MAX had pCR while none of those whose tumors did not show any decrease in SUV-MAX had pCR.

Conclusions
A decrease in ΔSUV-MAX after only one week of RCT for LARC may be able to predict the achievement of pCR in the post-RCT surgical specimen. Validation in a larger independent cohort is planned.
A coarse-grained model for synergistic action of multiple enzymes on cellulose
Authors: Asztalos Andrea , Daniels Marcus , Sethi Anurag , Shen Tongye , Langan Paul , Redondo Antonio , Gnanakaran Sandrasegaram 
Published: August 2012

Abstract

Background
Degradation of cellulose to glucose requires the cooperative action of three classes of enzymes, collectively known as cellulases. Endoglucanases randomly bind to cellulose surfaces and generate new chain ends by hydrolyzing β-1,4-D-glycosidic bonds. Exoglucanases bind to free chain ends and hydrolyze glycosidic bonds in a processive manner releasing cellobiose units. Then, β-glucosidases hydrolyze soluble cellobiose to glucose. Optimal synergistic action of these enzymes is essential for efficient digestion of cellulose. Experiments show that as hydrolysis proceeds and the cellulose substrate becomes more heterogeneous, the overall degradation slows down. As catalysis occurs on the surface of crystalline cellulose, several factors affect the overall hydrolysis. Therefore, spatial models of cellulose degradation must capture effects such as enzyme crowding and surface heterogeneity, which have been shown to lead to a reduction in hydrolysis rates.

Results
We present a coarse-grained stochastic model for capturing the key events associated with the enzymatic degradation of cellulose at the mesoscopic level. This functional model accounts for the mobility and action of a single cellulase enzyme as well as the synergy of multiple endo- and exo-cellulases on a cellulose surface. The quantitative description of cellulose degradation is calculated on a spatial model by including free and bound states of both endo- and exo-cellulases with explicit reactive surface terms (e.g., hydrogen bond breaking, covalent bond cleavages) and corresponding reaction rates. The dynamical evolution of the system is simulated by including physical interactions between cellulases and cellulose.

Conclusions
Our coarse-grained model reproduces the qualitative behavior of endoglucanases and exoglucanases by accounting for the spatial heterogeneity of the cellulose surface as well as other spatial factors such as enzyme crowding. Importantly, it captures the endo-exo synergism of cellulase enzyme cocktails. This model constitutes a critical step towards testing hypotheses and understanding approaches for maximizing synergy and substrate properties with a goal of cost effective enzymatic hydrolysis.
Diabetic angiopathy and angiogenic defects
Authors: Xu Ling , Kanasaki Keizo , Kitada Munehiro , Koya Daisuke 
Published: August 2012

Abstract
Diabetes is one of the most serious health problems in the world. A major complication of diabetes is blood vessel disease, termed angiopathy, which is characterized by abnormal angiogenesis. In this review, we focus on angiogenesis abnormalities in diabetic complications and discuss its benefits and drawbacks as a therapeutic target for diabetic vascular complications. Additionally, we discuss glucose metabolism defects that are associated with abnormal angiogenesis in atypical diabetic complications such as cancer.
The effects of MicroRNA transfections on global patterns of gene expression in ovarian cancer cells are functionally coordinated
Authors: Shahab Shubin W , Matyunina Lilya V , Hill Christopher G , Wang Lijuan , Mezencev Roman , Walker L DeEtte , McDonald John F 
Published: August 2012

Abstract

Background
MicroRNAs (miRNAs) are a class of small RNAs that have been linked to a number of diseases including cancer. The potential application of miRNAs in the diagnostics and therapeutics of ovarian and other cancers is an area of intense interest. A current challenge is the inability to accurately predict the functional consequences of exogenous modulations in the levels of potentially therapeutic miRNAs.

Methods
In an initial effort to systematically address this issue, we conducted miRNA transfection experiments using two miRNAs (miR-7, miR-128). We monitored the consequent changes in global patterns of gene expression by microarray and quantitative (real-time) polymerase chain reaction. Network analysis of the expression data was used to predict the consequence of each transfection on cellular function and these predictions were experimentally tested.

Results
While ~20% of the changes in expression patterns of hundreds to thousands of genes could be attributed to direct miRNA-mRNA interactions, the majority of the changes are indirect, involving the downstream consequences of miRNA-mediated changes in regulatory gene expression. The changes in gene expression induced by individual miRNAs are functionally coordinated but distinct between the two miRNAs. MiR-7 transfection into ovarian cancer cells induces changes in cell adhesion and other developmental networks previously associated with epithelial-mesenchymal transitions (EMT) and other processes linked with metastasis. In contrast, miR-128 transfection induces changes in cell cycle control and other processes commonly linked with cellular replication.

Conclusions
The functionally coordinated patterns of gene expression displayed by different families of miRNAs have the potential to provide clinicians with a strategy to treat cancers from a systems rather than a single gene perspective.