bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central role of mitochondrial injury in the pathogenesis of acute pancreatitis
Authors: Maléth J. , Rakonczay Z. , Venglovecz V. , Dolman N. J. , Hegyi P. 
Published: November 2012

AbstractAcute pancreatitis is an inflammatory disease with no specific treatment. One of the main reasons behind the lack of specific therapy is that the pathogenesis of acute pancreatitis is poorly understood. During the development of acute pancreatitis, the disease‐inducing factors can damage both cell types of the exocrine pancreas, namely the acinar and ductal cells. Because damage of either of the cell types can contribute to the inflammation, it is crucial to find common intracellular mechanisms that can be targeted by pharmacological therapies. Despite the many differences, recent studies revealed that the most common factors that induce pancreatitis cause mitochondrial damage with the consequent breakdown of bioenergetics, that is, ATP depletion in both cell types. In this review, we summarize our knowledge of mitochondrial function and damage within both pancreatic acinar and ductal cells. We also suggest that colloidal ATP delivery systems for pancreatic energy supply may be able to protect acinar and ductal cells from cellular damage in the early phase of the disease. An effective energy delivery system combined with the prevention of further mitochondrial damage may, for the first time, open up the possibility of pharmacological therapy for acute pancreatitis, leading to reduced disease severity and mortality.
The discovery of a new class of synaptic transmitters in smooth muscle 50 years ago and amelioration of coronary artery thrombosis
Authors: Bennett M. R. 
Published: November 2012

AbstractClopidogrel and ticagrelor, antagonists to P2Y12 receptor molecules on platelet membranes, significantly ameliorate acute myocardial infarction due to coronary artery thrombosis, the most common cause of death in the developed world. A personal account is given here of the foundational research that lead to the identification of P2Y receptors, carried out 50 years ago in the Melbourne University Zoology Department headed by Geoffrey Burnstock. In Christmas 1962, I made the serendipitous observation of large hyperpolarizing changes across the membranes of smooth muscle cells in the taenia coli of the intestine on stimulating its nerve supply. I then showed that these potentials relaxed the muscle and were not due to noradrenaline or acetylcholine, which were then the only substances known to be released from nerves. I called these non‐adrenergic, non‐cholinergic (NANC) terminals in the laboratory and showed that this NANC transmitter acted at receptor molecules on the muscle cells, promoting efflux of potassium ions, and so the observed potential changes. In 1968, Graeme Campbell showed that ATP relaxed the taenia coli muscle, and in 1969, David Satchell, using purine chromatography, showed that ATP was likely to be released from NANC terminals. The receptor molecules involved were shown to be exceptionally sensitive to 2‐methylthio‐ATP (Satchell and Macguire, 1975, J Pharmacol Exp Ther, 195, 540), and so belonged to the class P2Y receptors as designated by Abbracchio and Burnstock, with subclasses P2Y1–P2Y12. The discovery of the role of P2Y12 receptors in increasing thrombosis lead to the focused research that resulted in clopidogrel and ticagrelor.
Heat stress activates the Akt/mTOR signalling pathway in rat skeletal muscle
Authors: Yoshihara T. , Naito H. , Kakigi R. , Ichinoseki‐Sekine N. , Ogura Y. , Sugiura T. , Katamoto S. 
Published: November 2012

AbstractAimIt is well known that various stimuli, such as mechanical stress and nutrients, induce muscle hypertrophy thorough the Akt/mTOR signalling pathway, which is a key mediator of protein synthesis and hypertrophy in skeletal muscle. It was recently reported that heat stress also induces an increase in muscle weight and muscle protein content. In addition, heat stress enhances Akt/mTOR signalling after one bout of resistance exercise. However, it remains unclear whether increased temperature itself stimulates the Akt/mTOR signalling pathway.MethodsForty‐two male Wistar rats (279.5 ± 1.2 g) were divided into a control group (CON) or one of five thermal stress groups at 37, 38, 39, 40 or 41 °C (n = 7 each group). After overnight fasting, both legs were immersed in different temperatures of hot water for 30 min under sodium pentobarbital anaesthesia. The soleus and plantaris muscles were immediately removed from both legs after the thermal stress.ResultsThe phosphorylation of mTOR or 4E‐BP1 and heat shock protein (HSP) expression levels were similar among groups in both the soleus and plantaris muscles. However, Akt and p70S6K phosphorylation significantly increased at 41 °C in the soleus and plantaris muscles. Moreover, we observed a temperature‐dependent increase in Akt and p70S6K phosphorylation in both muscles.ConclusionOur data indicate that the altered temperature increased phosphorylation in a temperature‐dependent manner in rat skeletal muscle and may itself be a key stimulator of Akt/mTOR signalling.
Significant association of close homologue of L1 gene polymorphism rs2272522 with schizophrenia in Qatar
Authors: Shaltout Taher E. , Alali Khalid Abdulla , Bushra Sumbul , Alkaseri Aisha Mubarak , Jose Elizabeth Divya , Al‐Khainji Mozza , Saleh Randah , Salama Dahir Amany , Shaltout Hany , Al‐Abdullah Maged , Rizk Nasser M. 
Published: November 2012

AbstractIntroductionPrevious reports have found that polymorphisms in the close homologue of L1 (CHL1) gene located on chromosome 3p26 are associated with schizophrenia among different ethnic populations. The aim of this study was to examine the associations of single nucleotides polymorphisms (SNPs) of the CHL1 gene locus, including rs2055314 (C/T), rs2272522 (C/T) and rs331894 (A/G), with schizophrenia in the Qatari population.MethodsAn association case control study was carried out on 86 Qatari schizophrenic patients from the Psychiatry Hospital, Hammed Medical Corporation, Qatar and 88 Qatari unrelated, healthy, control subjects. Schizophrenia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM‐IV) criteria for schizophrenia by two independent psychiatrists. Genotyping of the SNPs rs2055314 (C/T), rs2272522 (C/T) and rs331894 (A/G) was conducted using the 5′ nuclease assay with the TaqMan MGB probe and an ABI 7500.ResultsIndividuals with the rs2272522 TT genotype had approximately 4.2 times greater risk of schizophrenia compared to individuals with the CC genotype (OR = 4.21; 95% CI: 1.12–15.53; P = 0.047). In addition, individuals carrying a T allele of the rs2272522 SNP had a significantly increased risk of schizophrenia (1.78 times) among the population (P = 0.028). SNPs rs2055314 and rs331894 had no significant association with schizophrenia. Pairwise linkage disequilibrium (LD) between the three polymorphisms was modest in the schizophrenic group.DiscussionThe rs2272522 polymorphism was found to exhibit a highly significant association with schizophrenia in the Qatari population. This finding supports the hypothesis that cell adhesion molecules may be involved in the etiology of this disease among Qatari patients.
Romiplostim dose–response in patients with myelodysplastic syndromes
Authors: Perez Ruixo Juan Jose , Doshi Sameer , Wang Yow‐Ming C. , Mould Diane R. 
Published: November 2012

AimTo characterize the romiplostim dose–response in subjects with low or intermediate‐1 risk myelodysplastic syndromes (MDS) receiving subcutaneous romiplostim.MethodsData from 44 MDS subjects receiving subcutaneous romiplostim (dose range 300–1500 μg week−1) were used to develop a pharmacodynamic model consisting of a romiplostim‐sensitive progenitor cell compartment linked to the peripheral blood compartment through four transit compartments representing the maturation in the bone marrow from megakaryocytes to platelets. A kinetics of drug effect model was used to quantify the stimulatory effect of romiplostim on the proliferation of sensitive progenitor cells and pharmacodynamics‐mediated disposition was modelled by assuming the kinetics of drug effect constant (kDE) to be proportional to the change in platelet count relative to baseline.ResultsThe estimated values (between subject variability) for baseline platelet count, mean transit time, and kDE were 24 × 109 l−1 (47%), 9.6 days (44%) and 0.28 days−1, respectively. MDS subjects had a shorter platelet lifespan (42 h) than healthy subjects (257 h). Romiplostim effect was described for responders (78%) and non‐responders (22%). The average weekly stimulatory effect of romiplostim on the production rate of sensitive progenitor cells at baseline was 269% per 100 μg week−1 for responders. Body weight, age, gender and race were not statistically related to romiplostim pharmacodynamic parameters. Visual predictive checks confirmed the model adequacy.ConclusionThe time course of platelet counts in MDS subjects receiving subcutaneous administration of escalating doses of romiplostim was characterized and showed a linear dose–response for romiplostim responders to increase the platelet counts.
Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives
Authors: Tighe Sarah K , Reading Sarah A , Rivkin Paul , Caffo Brian , Schweizer Barbara , Pearlson Godfrey , Potash James B , DePaulo J Raymond , Bassett Susan S 
Published: November 2012

Tighe SK, Reading SA, Rivkin P, Caffo B, Schweizer B, Pearlson G, Potash JB, DePaulo J Raymond, Bassett SS.  Total white matter hyperintensity volume in bipolar disorder patients and their healthy relatives.  Bipolar Disord 2012: 14: 888–893. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd.Objectives: White matter hyperintensities (WMH) are more common in subjects with bipolar disorder (BP) than in healthy subjects (HS). Few studies have examined the effect of the diagnostic type of bipolar illness on WMH burden, and none have approached this question through a direct measurement of the volume of affected white matter in relationship to familiality. In this pilot study, we utilized a volumetric measurement of WMH to investigate the relationship between the total volume of WMH and the familiality and type of BP.Methods: Forty‐five individuals with bipolar I disorder (BP‐I) with psychotic features, BP‐I without psychotic features, or bipolar II disorder (BP‐II), seven of their unaffected relatives, and 32 HS were recruited for participation. T‐2 weighted magnetic resonance imaging scans were obtained on all subjects, and the total volume of all WMH for each subject was measured in cubic centimeters. The significance of difference between groups was tested using ANOVA with post‐hoc adjustment for multiple comparisons. Further, we used logistic regression to test for trends between symptom load and total WMH volume.Results: The mean total volume of WMH in BP‐I patients with psychotic features was significantly higher (p < 0.05) than that of HS. Further, we observed a positive linear trend by familiality and type of affectedness when comparing mean total WMH volume of HS, unaffected family members, subjects with BP‐II, and BP‐I with and without a history of psychosis (p < 0.05).Conclusions: Based on a quantitative technique, WMH burden appears to be associated with familiality and type of BP. The significance of these findings remains to be fully elucidated.
Promoting fruit and vegetable consumption: The role of message framing and autonomy
Authors: Churchill Sue , Pavey Louisa 
Published: November 2012

ObjectivePrevious studies have shown that gain‐framed messages (vs. loss‐framed messages) are more effective when advocating ‘low‐risk’ prevention behaviours (e.g., diet, exercise, dental flossing) that minimize the risk of a health problem.The objective of the reported research was to explore whether autonomy moderated the effectiveness of gain‐framed vs. loss‐framed messages encouraging fruit and vegetable consumption.DesignA prospective design was used for this study.MethodAt time 1, participants (N = 177) completed a measure of autonomy and read either a gain‐framed message (describing the benefits of fruit and vegetable consumption) or a loss‐framed message (describing the disadvantages of not eating fruit and vegetables). At time 2, participants reported their fruit and vegetable consumption over the preceding 7 days.ResultsAutonomy moderated the effect of message framing. Gain‐framed messages only prompted fruit and vegetable consumption amongst those with high levels of autonomy.ConclusionThe study identifies a key role for autonomy in shaping recipients' responses to framed messages promoting fruit and vegetable consumption.Statement of contributionWhat is already known on this subject? Previous studies have shown that gain‐framed messages (vs. loss framed messages) are more effective when advocating low‐risk prevention behaviours (e.g., diet, exercise, dental flossing) that minimize the risk of a health problem.What does this study add? The current study is the first to demonstrate that the success of a gain‐framed message to promote fruit and vegetable consumption is dependent on recipients' level of autonomy.
Identification and profiling of CXCR3–CXCR4 chemokine receptor heteromer complexes
Authors: Watts AO , van Lipzig MMH , Jaeger WC , Seeber RM , van Zwam M , Vinet J , van der Lee MMC , Siderius M , Zaman GJR , Boddeke HWGM , Smit MJ , Pfleger KDG , Leurs R , Vischer HF 
Published: November 2012

Background and PurposeThe C‐X‐C chemokine receptors 3 (CXCR3) and C‐X‐C chemokine receptors 4 (CXCR4) are involved in various autoimmune diseases and cancers. Small antagonists have previously been shown to cross‐inhibit chemokine binding to CXCR4, CC chemokine receptors 2 (CCR2) and 5 (CCR5) heteromers. We investigated whether CXCR3 and CXCR4 can form heteromeric complexes and the binding characteristics of chemokines and small ligand compounds to these chemokine receptor heteromers.Experimental ApproachCXCR3–CXCR4 heteromers were identified in HEK293T cells using co‐immunoprecipitation, time‐resolved fluorescence resonance energy transfer, saturation BRET and the GPCR‐heteromer identification technology (HIT) approach. Equilibrium competition binding and dissociation experiments were performed to detect negative binding cooperativity.Key ResultsWe provide evidence that chemokine receptors CXCR3 and CXCR4 form heteromeric complexes in HEK293T cells. Chemokine binding was mutually exclusive on membranes co‐expressing CXCR3 and CXCR4 as revealed by equilibrium competition binding and dissociation experiments. The small CXCR3 agonist VUF10661 impaired binding of CXCL12 to CXCR4, whereas small antagonists were unable to cross‐inhibit chemokine binding to the other chemokine receptor. In contrast, negative binding cooperativity between CXCR3 and CXCR4 chemokines was not observed in intact cells. However, using the GPCR‐HIT approach, we have evidence for specific β‐arrestin2 recruitment to CXCR3‐CXCR4 heteromers in response to agonist stimulation.Conclusions and ImplicationsThis study indicates that heteromeric CXCR3–CXCR4 complexes may act as functional units in living cells, which potentially open up novel therapeutic opportunities.
Meconium microbiota types dominated by lactic acid or enteric bacteria are differentially associated with maternal eczema and respiratory problems in infants
Authors: Gosalbes M. J. , Llop S. , Vallès Y. , Moya A. , Ballester F. , Francino M. P. 
Published: November 2012

SummaryBackgroundCulture‐dependent methods have shown that meconium, the newborn's first intestinal discharge, is not sterile, but the diversity of bacteria present in this material needs to be further characterized by means of more sensitive molecular techniques.ObjectiveOur aims were to characterize molecularly the meconium microbiota in term infants, to assess whether it contributes to the future microbiota of the infants’ gastrointestinal tract, and to evaluate how it relates to lifestyle variables and atopy‐related conditions.MethodsWe applied high‐throughput pyrosequencing of the 16S rRNA gene to study the meconium microbiota in twenty term newborns from a Spanish birth cohort. For comparison, we characterized the microbiota in fecal samples from seven pregnant women days before delivery and in two series of infant samples spanning the first seven months of life. We also compared our data with vaginal and skin microbiota characterized in independent studies. Different types of meconium microbiota were defined based on taxonomic composition and abundance and their associations with different factors were statistically evaluated.ResultsThe meconium microbiota differs from those in adult feces, vagina and skin, but resembles that of fecal samples from young infants. Meconium samples clustered into two types with different bacterial diversity, richness and composition. One of the types was less diverse, dominated by enteric bacteria and associated with a history of atopic eczema in the mother (P = 0.038), whereas the second type was dominated by lactic acid bacteria and associated with respiratory problems in the infant (P = 0.040).Conclusions & Clinical RelevanceOur findings suggest that the meconium microbiota has an intrauterine origin and participates in gut colonization. Although based on a small population sample, our association analyses also suggest that the type of bacteria detected in meconium is influenced by maternal factors and may have consequences for childhood health.
CXCR3 axis in patients with primary biliary cirrhosis: a possible novel mechanism of the effect of ursodeoxycholic acid
Authors: Manousou P , Kolios G , Drygiannakis I , Koulentaki M , Pyrovolaki K , Voumvouraki A , Notas G , Bourikas L , Papadaki H A , Kouroumalis E 
Published: November 2012

SummaryThe CXC chemokines, monokine induced by interferon (IFN)-gamma (MIG) (CXCL9), IFN-gamma-induced protein 10 (IP-10) (CXCL10) and IFN-inducible T cell alpha chemoattractant (I-TAC) (CXCL11), are known to attract CXCR3- (CXCR3A and CXCR3B) T lymphocytes. We investigated MIG, IP-10 and I-TAC mRNAs expression by semi-quantitative multiplex reverse transcription–polymerase chain reaction (RT–PCR) in liver biopsies obtained from patients with a first diagnosis of primary biliary cirrhosis [(PBC) = 20] compared to patients with normal liver biopsy [normal controls (NCs) = 20]. Chemokine production was assessed by enzyme-linked immunosorbent assay (ELISA) in serum. Measurements were repeated 6 months after ursodeoxycholic acid (UDCA) treatment in PBC patients. CXCR3A and CXCR3B mRNAs expression was examined in immunomagnetically sorted CD3+ peripheral blood lymphocytes (PBL) pre- and post-treatment by RT–PCR. Flow cytometry was used to evaluate the expression of CXCR3+ PBLs of NCs and PBC patients. A marked mRNA expression of MIG and IP-10 was found in PBC patients. I-TAC mRNA was not detected. In serum of PBC patients there was a significant increase of MIG and IP-10 compared to NCs. Interestingly, there was a significant reduction of these proteins in patients' serum after UDCA treatment. I-TAC was not statistically different between groups. CXCR3A mRNA expression was found in PBLs from PBC patients as well as in NCs. CXCR3B mRNA was expressed in four of 20 (19%) NCs and 20 of 20 PBC patients. Flow cytometry revealed a significantly lower CXCR3 expression in NCs (13·5%) than in PBC (37·2%), which was reduced (28·1%, P &lt; 0·01) after UDCA administration. These data suggest a possible role for CXCR3-binding chemokines and their receptor in the aetiopathogenetic recruitment of lymphocytes in PBC and a new mechanism of action for UDCA.
Effect of Low Direct Current on Anaerobic Multispecies Biofilm Adhering to a Titanium Implant Surface
Authors: Sahrmann Philipp , Zehnder Matthias , Mohn Dirk , Meier André , Imfeld Thomas , Thurnheer Thomas 
Published: November 2012

AbstractPurposePeri‐implantitis is caused by biofilm adhering to the implant. It has been shown that bactericidal electrolysis products are generated when a low direct current is applied to a titanium implant used as the anode. The hypothesis of this study was that low‐current electrolysis would eradicate viable bacteria in a simulated subgingival multispecies biofilm adhering to a titanium implant surface.Material and MethodsBiofilms consisting of eight anaerobic species were grown on pellicle‐coated titanium discs with sand‐blasted, acid‐etched, large‐grit (SLA; Straumann, Basel, Switzerland) surface. After 40.5 hours of growth, discs were treated with 10 mA for 10 minutes in an electrolytical setup with physiological saline and gelatin.ResultsLow direct current at discs used as the cathode caused a reduction of three to four orders of magnitude in viable counts, while no viable bacteria were recovered from anode discs (Mann–Whitney U‐test, p < .01). Confocal laser scanning microscopy in combination with a live/dead stain showed biofilm detachment at the cathode and reduced viability at the anode.ConclusionElectrochemical treatment of diseased implants appears to be promising and well worth investigating further.
Deviations between Placed and Planned Implant Positions: An Accuracy Pilot Study of Skeletally Supported Stereolithographic Surgical Templates
Authors: Stübinger Stefan , Buitrago‐Tellez Carlos , Cantelmi Gianni 
Published: November 2012

AbstractPurposeThe aim of the present study was to evaluate deviations between virtually planned and placed implants by the use of skeletally supported stereolithographic templates.Materials and MethodsTen consecutive patients were selected for virtual three‐dimensional implant planning using the FacilitateTM software (Astra Tech AB, Mölndal, Sweden). Computer tomography images were obtained in the pre‐ and postoperative phase. Four deviation parameters (i.e. global, angular, depth, and lateral deviation) were defined and calculated between the planned and the placed implants, using the coordinates of their respective apical and coronal points.ResultsDeviations at the coronal positions appeared to be smaller (95% confidence interval: 0.15–1.0) as compared with apical positions (95% confidence interval: 0.14–1.1). But only the difference with regard to lateral measurements appeared to be statistically significant (p = .03). Except for depth (p = .01), no significant association between mesial or more distal locations could be detected concerning global (p = .07), lateral (p = .87), and angular (p = .56) values in mixed model analyses. Overall, there was a slight tendency for higher values for more distal locations.ConclusionAs slight deviations between planned and placed implants especially may occur even with skeletal‐supported templates, the clinician should be aware not to overestimate advocated surgical safety by using static navigation tools.