bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide
Authors: De Geyter Deborah , Stoop Wendy , Zgavc Tine , Sarre Sophie , Michotte Yvette , De Keyser Jacques , Kooijman Ron
Published: August 2012

Background

For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals.

Methods

The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein.

Results and conclusions

The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria.
Does duration of untreated psychosis predict very long term outcome of schizophrenic disorders? results of a retrospective study
Authors: Primavera Diego , Bandecchi Chiara , Lepori Tiziana , Sanna Lucia , Nicotra Eraldo , Carpiniello Bernardo
Published: August 2012

Background

Studies performed to assess the relevance of duration of untreated psychosis (DUP) as a predictor of long-term outcome (i.e. follow-ups of ten years or more) are somewhat limited. The aim of this study was to evaluate the potential association between DUP and very long-term outcome (16-33 yrs) of schizophrenia by means of a retrospective design.

Methods

Retrospective data obtained from clinical records were collected regarding DUP and outcome variables (number of hospitalizations; number of attempted suicides; course of illness; GAF scores at last observation) for a cohort of 80 outpatients (52 Males, 28 Females, mean age 51.0+/-11.58 years) affected by schizophrenia according to DSMIVTR attending a university community mental health centre.

Results

Mean duration of follow up was 25.2 +/- 8.68 years; mean duration of untreated psychosis was 49.00 months (range 1-312 mo), with no significant difference according to gender. Patients with a shorter DUP (=/< 1 year) displayed more frequent “favourable” courses of illness (28.9% vs 8.6%) (p = 0.025), more frequent cases with limited (=/< 3) number of hospital admissions (85.7% vs 62.1%) (p = 0.047) and a better functioning (mean GAF score = 50.32+/-16.49 vs 40.26+/-9.60, p = 0.002); regression analyses confirmed that shorter DUP independently predicted a more positive outcome in terms of number of hospital admissions, course of illness, functioning (GAF scores).

Conclusion

A shorter DUP appears to act as a significant predictor of better outcome in schizophrenia even in the very long-term.
Cumulative keyboard strokes: a possible risk factor for carpal tunnel syndrome
Authors: Eleftheriou Andreas , Rachiotis George , Varitimidis Socratis E , Koutis Charilaos , Malizos Konstantinos N , Hadjichristodouloul Christos
Published: August 2012

Background

Contradictory reports have been published regarding the association of Carpal Tunnel Syndrome (CTS) and the use of computer keyboard. Previous studies did not take into account the cumulative exposure to keyboard strokes among computer workers. The aim of the present study was to investigate the association between cumulative keyboard use (keyboard strokes) and CTS.

Methods

Employees (461) from a Governmental data entry & processing unit agreed to participate (response rate: 84.1 %) in a cross-sectional study. Α questionnaire was distributed to the participants to obtain information on socio-demographics and risk factors for CTS. The participants were examined for signs and symptoms related to CTS and were asked if they had previous history or surgery for CTS. The cumulative amount of the keyboard strokes per worker per year was calculated by the use of payroll’s registry. Two case definitions for CTS were used. The first included subjects with personal history/surgery for CTS while the second included subjects that belonged to the first case definition plus those participants were identified through clinical examination.

Results

Multivariate analysis used for both case definitions, indicated that those employees with high cumulative exposure to keyboard strokes were at increased risk of CTS (case definition A: OR = 2.23;95 % CI = 1.09-4.52 and case definition B: OR = 2.41; 95%CI = 1.36-4.25). A dose response pattern between cumulative exposure to keyboard strokes and CTS has been revealed (p < 0.001).

Conclusions

The present study indicated a possible association between cumulative exposure to keyboard strokes and development of CTS. Cumulative exposure to key-board strokes would be taken into account as an exposure indicator regarding exposure assessment of computer workers. Further research is needed in order to test the results of the current study and assess causality between cumulative keyboard strokes and development of CT.
Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes
Authors: Korsak Kris , Dolatshad Nazanin F , Silva Ayona T , Saffrey M Jill
Published: August 2012

Background

Ageing is associated with gastrointestinal dysfunction, which can have a major impact on quality of life of the elderly. A number of changes in the innervation of the gut during ageing have been reported, including neuronal loss and degenerative changes. Evidence indicates that reactive oxygen species (ROS) are elevated in ageing enteric neurons, but that neurotrophic factors may reduce generation of neuronal ROS. Two such factors, glial cell line derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) have also been found to protect enteric neurons against oxidative stress induced cell death of enteric ganglion cells in vitro. We have investigated the possible roles of neurotrophic factors further, by examining their expression in the gut during ageing, and by analysing their effects on antioxidant enzyme production in cultures of enteric ganglion cells.

Results

Analysis of the expression of GDNF and its receptors c-Ret and GFR α − 1 in rat gut by RT-PCR showed that expression continues throughout life and into ageing, in both ad libitum(AL) and calorically-restricted (CR) animals. Levels of expression of GDNF and GFR α − 1 were elevated in 24 month AL animals compared to 24 month CR animals, and to 24 CR and 6 month control animals respectively. The related factor Neurturin and its receptor GFR α − 2 were also expressed throughout life, the levels of the GFR – α-2(b) isoform were reduced in 24 m AL animals. Immunolabelling showed that c-Ret and GFR α − 1 proteins were expressed by myenteric neurons in ageing animals. GDNF, but not NT-3, was found to increase expression of Cu/Zn superoxide dismutase and catalase by cultured enteric ganglion cells.

Conclusions

The neurotrophic factors GDNF and neurturin and their receptors continue to be expressed in the ageing gut. Changes in the levels of expression of GDNF , GFR α-1 and GFR α-2(b) isoform occurred in 24 m AL animals. GDNF, but not NT-3, increased the levels of antioxidant enzymes in cultured enteric ganglion cells, indicating a possible mechanism for the reported protective effect of GDNF against menadione-induced neuronal apoptosis in the ageing gut. Together these data suggest that GDNF family members may play a protective role in the gut throughout life, and support the suggestion that dysregulation of neurotrophic factor support could contribute to neuronal ageing in the gut.
Non-isothermal kinetics of thermal degradation of chitosan
Authors: Georgieva Velyana , Zvezdova Dilyana , Vlaev Lyubomir
Published: August 2012

Background

Chitosan is the second most abundant nitrogen containing biopolymer in nature, obtained from the shells of crustaceans, particularly crabs, shrimp and lobsters, which are waste products of seafood processing industries. It has great potential application in the areas of biotechnology, biomedicine, food industries, and cosmetics. Chitosan is also capable of adsorbing a number of metal ions as its amino groups can serve as chelation sites. Grafted functional groups such as hydroxyl, carboxyl, sulfate, phosphate, and amino groups on the chitosan have been reported to be responsible for metal binding and sorption of dyes and pigments. The knowledge of their thermal stability and pyrolysis may help to better understand and plan their industrial processing.

Results

Thermogravimetric studies of chitosan in air atmosphere were carried out at six rates of linear increasing of the temperature. The kinetics and mechanism of the thermal decomposition reaction were evaluated from the TG data using recommended from ICTAC kinetics committee iso-conversional calculation procedure of Kissinger-Akahira-Sunose, as well as 27 mechanism functions. The comparison of the obtained results showed that they strongly depend on the selection of proper mechanism function for the process. Therefore, it is very important to determine the most probable mechanism function. In this respect the iso-conversional calculation procedure turned out to be the most appropriate.

Conclusion

Chitosan have excellent properties such as hydrophilicity, biocompatibility, biodegradability, antibacterial, non-toxicity, adsorption application. The thermal degradation of chitosan occurs in two stages. The most probable mechanism function for both stages is determined and it was best described by kinetic equations of n
-th order (F
n mechanism). For the first stage, it was established that n is equal to 3.0 and for the second stage – to 1.0 respectively. The values of the apparent activation energy E, pre-exponential factor A in Arrhenius equation, as well as the changes of entropy ΔS
≠, enthalpy ΔH
≠ and free Gibbs energy ΔG
≠ for the formation of the activated complex from the reagent are calculated.
Giant cystic meconium peritonitis presenting in a neonate with classic radiographic eggshell calcifications and treated with an elective surgical approach: a case report
Authors: Barthel Erik R , Speer Allison L , Levin Daniel E , Naik-Mathuria Bindi J , Grikscheit Tracy C
Published: August 2012

Introduction

Giant cystic meconium peritonitis is relatively rare. Patients often present with nonspecific physical findings such as distension and emesis. Plain abdominal films remain invaluable for identifying the characteristic calcifications seen with a meconium pseudocyst, and large eggshell calcifications are pathognomonic for the giant cystic subtype.

Case presentation

We present classic plain X-ray findings and an intraoperative image of a premature low birth weight two-day-old Hispanic male baby treated for giant cystic meconium peritonitis with a staged procedure involving peritoneal drainage, ostomy creation and closure.

Conclusion

Pediatric surgeons have a range of potential therapeutic approaches for giant cystic meconium peritonitis. A delay of definitive surgical management in the setting of massive abdominal soiling is a safe and acceptable strategy if adequate temporizing drainage is performed in the early perinatal period.
Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies
Authors: Xuan Li , Huang Fen , Fan Zhiping , Zhou Hongsheng , Zhang Xian , Yu Guopan , Zhang Yu , Liu Can , Sun Jing , Liu Qifa
Published: August 2012

Background

Intensified conditioning regimens (increasing the intensity of standard myeloablative conditioning) for hematological malignancies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) could reduce the relapse rate of the underlying disease, but it might simultaneously increase the transplant-related mortality including the mortality of infections. To explore whether intensified conditioning affected Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, 185 patients undergoing allo-HSCT were enrolled.

Methods

A total of 104 cases received standard and 81 intensified conditioning. Cyclosporine A (CsA) withdrawal and/or donor lymphocyte infusion (DLI) were conducted in high-risk patients. The EBV-DNA and CMV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR) and immune reconstitution of recipients were analyzed by flow cytometry.

Results

The 3-year cumulative incidence of EBV viremia, EBV-associated diseases and mortality of EBV-associated diseases were 25.3% ± 4.6%, 10.5% ± 3.4% and 0.0% ± 0.0% in the standard group, compared with 45.6% ± 6.5%, 26.0% ±5.3% and 7.3% ± 3.1% in the intensified group (P = 0.002, P = 0.002, P = 0.008). The 3-year cumulative incidence of CMV viremia and CMV-associated diseases, mortality of CMV-associated diseases and incidence of bacterial and fungal infections were similar between the two groups (P = 0.855, P = 0.581, P = 0.933, P = 0.142, P = 0.182, respectively). Multivariate analysis showed that intensified conditioning was one of the risk factors for EBV viremia and EBV-associated diseases (P = 0.037, P = 0.037), but it had no effects on CMV infections. The percentage of CD4+ T cells and CD4+/CD8+ ratio at 3 months post-transplantation were lower in the intensified group (P = 0.032, P = 0.022). The 3-year OS and DFS in the standard group were 62.2% ± 5.8% and 60.6% ± 5.6%, compared with 51.6% ± 6.2% and 51.1% ± 5.9% in the intensified group (P = 0.029, P = 0.063).

Conclusions

Intensified conditioning represents a promising approach for high-risk hematological malignancies, although it affects early immune reconstitution of recipients and increases the incidence and mortality of EBV infections.
The relationship between the activates of antioxidant enzymes in red blood cells and body mass index in Iranian type 2 diabetes and healthy subjects
Authors: Taheri Ehsaneh , Djalali Mahmoud , Saedisomeolia Ahmad , Moghadam Ali Malekshahi , Djazayeri Abolghasem , Qorbani Mostafa
Published: August 2012

Background

Diabetes mellitus is a metabolic disorder characterized by increased production of free radicals and oxidative stress. The aim of this study was to evaluate the activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxide (GSH-PX) in type 2 diabetic patients compared with healthy subjects.

Methods

This cross-sectional study was conducted on 100 type 2 diabetic patients and 100 healthy controls. Total antioxidant capacity and fasting serum levels of SOD, GR, and GSH-Px were measured. All data were analyzed using SPSS software compatible with Microsoft Windows.

Results

The activity levels of SOD were lower in diabetic patients (111.93 ± 354.99 U/g Hb) than in healthy controls (1158.53 ± 381.21 U/g Hb), but this was not significant. Activity levels of GSH-PX and GR in diabetics (62.33 ± 36.29 and 7.17 ± 5.51 U/g Hb, respectively) were higher than in controls (24.62 ± 11.2 and 3.16 ± 2.95 U/g Hb, respectively). The statistical difference in enzyme activity of both GSH-Px and GR was significant (P <0.05).

Conclusion

The increasing production of free radicals and changes in activity levels of antioxidant enzymes in order to scavenge free radicals and/or the effect of diabetes on the activity levels of antioxidant enzymes has an important effect on diabetic complications and insulin resistance. Evaluation of the levels of antioxidant enzymes and antioxidant factors in patients at different stages of the disease, and pharmaceutical and nutritional interventions, can be helpful in reducing oxidative stress in type 2 diabetic patients. There were positive relationship between BMI and the activity of antioxidant enzymes including SOD, GR and GPX in both groups.
FGD1 as a central regulator of extracellular matrix remodelling – lessons from faciogenital dysplasia
Authors: Genot Elisabeth , Daubon Thomas , Sorrentino Vincenzo , Buccione Roberto
Published: August 2012

Disabling mutations in the FGD1 gene cause faciogenital dysplasia (also known as Aarskog-Scott syndrome), a human X-linked developmental disorder that results in disproportionately short stature, facial, skeletal and urogenital anomalies, and in a number of cases, mild mental retardation. FGD1 encodes the guanine nucleotide exchange factor FGD1, which is specific for the Rho GTPase cell division cycle 42 (CDC42). CDC42 controls cytoskeleton-dependent membrane rearrangements, transcriptional activation, secretory membrane trafficking, G1 transition during the cell cycle and tumorigenic transformation. The cellular mechanisms by which FGD1 mutations lead to the hallmark skeletal deformations of faciogenital dysplasia remain unclear, but the pathology of the disease, as well as some recent discoveries, clearly show that the protein is involved in the regulation of bone development. Two recent studies unveiled new potential functions of FGD1, in particular, its involvement in the regulation of the formation and function of invadopodia and podosomes, which are cellular structures devoted to degradation of the extracellular matrix in tumour and endothelial cells. Here, we discuss the hypothesis that FGD1 might be an important regulator of events controlling extracellular matrix remodelling and possibly cell invasion in physiological and pathological settings. Additionally, we focus on how studying the cell biology of FGD1 might help us to connect the dots that link CDC42 signalling with remodelling of the extracellular matrix (ECM) in physiology and complex diseases, while, at the same time, furthering our understanding of the pathogenesis of faciogenital dysplasia.
S-Glutathionylation of LMW-PTP regulates VEGF-mediated FAK activation and endothelial cell migration
Authors: Abdelsaid Mohammed A. , El-Remessy Azza B.
Published: August 2012

Although promising, the ability to regulate angiogenesis via delivery of VEGF remains unrealized goal. We have shown previously that physiological levels of peroxynitrite (PN,1 µM) are required for VEGF-mediated angiogenic response, yet the redox-regulated mechanisms governing VEGF signal remain unexplored. We assessed the impact of VEGF and peroxynitrite on modifying redox-state, reduced-glutathion (GSH) and S-glutathionylation on regulation of the low molecular weight protein tyrosine phosphatase (LMW-PTP) and focal adhesion kinase (FAK), key mediators of VEGF-mediated cell migration. Stimulation of human microvascular endothelial (HME) with VEGF (20 ng/ml) or PN (1 µM) caused immediate and reversible negative-shift in cellular redox-state and thiol oxidation of LMW-PTP that culminated in cell migration. VEGF causes reversible S-glutathionylation of LMW-PTP that inhibited its phosphorylation and activity and caused transient FAK activation. Modulating redox-state by decomposing peroxynitrite (FeTPPS, 2.5 µM) or GSH-precursor (NAC, 1 mM) caused positive-shift of redox-state and prevented VEGF-mediated S-glutathionylation and oxidative inhibition of LMW-PTP. NAC and FeTPPS prevented FAK activation, its association with LMW-PTP and cell migration. Inhibiting LMW-PTP expression markedly enhanced FAK activation and cell migration. While mild oxidative stress achieved by combining VEGF with 0.1–0.2 mM PN augmented cell migration, acute shift to oxidative stress achieved by combining VEGF with 0.5 mM PN induced and sustained FAK activation, LMW-PTP S-glutathionylation resulting in LMW-PTP inactivation and inhibited cell migration. In conclusion, our findings demonstrate that balanced redox-state is required for VEGF to facilitate reversible S-glutathionylation of LMW-PTP, FAK activation and endothelial cell migration. Shifting redox-state to reductive stress or oxidative stress blunted VEGF-mediated angiogenic response.
Polo-like kinase is required for synaptonemal complex disassembly and phosphorylation in mouse spermatocytes
Authors: Jordan PW , Karppinen J , Handel MA
Published: August 2012

During meiosis, accurate coordination of the completion of homologous recombination and synaptonemal complex (SC) disassembly during the prophase to metaphase I (G2/MI) transition is essential to avoid aneuploid gametes and infertility. Previous studies have shown that kinase activity is required to promote meiotic prophase exit. The first step of the G2/MI transition is the disassembly of the central element components of the SC, however the kinase(s) required to trigger this process remains unknown. Here we assess roles of polo-like kinases (PLKs) in mouse spermatocytes, both in vivo and during prophase exit induced ex vivo by the phosphate inhibitor okadaic acid (OA). All four PLKs are expressed during the first wave of spermatogenesis. Only PLK1 (not PLK2-4) localizes to the SC during the G2/MI transition. The SC central element proteins SYCP1, TEX12 and SYCE1 are phosphorylated during the G2/MI transition. However, treatment of pachytene spermatocytes with the PLK inhibitor BI 2536 prevented the OA-induced meiotic prophase exit and inhibited phosphorylation of the central element proteins as well as their removal from the SC. Phosphorylation assays in vitro demonstrated that PLK1, but not PLK2-4, phosphorylates central element proteins SYCP1 and TEX12. These findings provide mechanistic details of the first stage of SC disassembly in mammalian spermatocytes, and reveal that PLK-mediated phosphorylation of central element proteins is required for meiotic prophase exit.
The conserved kinase SRPK regulates karyosome formation and spindle microtubule assembly in Drosophila oocytes
Authors: Loh Benjamin J. , Cullen C. Fiona , Vogt Nina , Ohkura Hiroyuki
Published: August 2012

In Drosophila oocytes, after the completion of recombination, meiotic chromosomes form a compact cluster called the karyosome within the nucleus, and later assemble spindle microtubules without centrosomes. Although these oocyte specific phenomena are also observed in humans, their molecular basis is not well understood. Here we report essential roles for the conserved kinase SRPK in both karyosome formation and spindle microtubule assembly in oocytes. We have identified a female sterile srpk mutant through a cytological screen for karyosome defects. Unlike most karyosome mutants, the karyosome defect is independent of the meiotic recombination checkpoint. Heterochromatin clustering found within the wild-type karyosome is disrupted in the mutant. Strikingly, a loss of SRPK severely prevents microtubule assembly for acentrosomal spindles in mature oocytes. Subsequently, bi-orientation and segregation of meiotic chromosomes are also defective. Therefore, this study demonstrates new roles of this conserved kinase in two independent meiotic steps specific to oocytes.
Krüppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor
Authors: Lai Jun-Kai , Wu Han-Chung , Shen Yuh-Chiang , Hsieh Hsin-Ying , Yang Shu-Yi , Chang Chia-Che
Published: August 2012

Hepatocyte growth factor/scatter factor (HGF) is unique by inducing epithelial cell scattering, a cellular event pivotal to HGF-mediated invasive-growth response essential for embryonic development and metastasis. Krüppel-like factor 4 (KLF4) is a multifunctional zinc-finger transcription factor involved in cell proliferation, differentiation and self-renewal. We herein present the first evidence for the functional connection between KLF4 and HGF-induced cell scattering. Particularly, we found that KLF4 was up-regulated by HGF in two independent epithelial cellular systems HepG2 and MDCK, whereas KLF4 knockdown inhibited HGF-induced E-cadherin suppression and cell scattering. Moreover, enforced nuclear KLF4 expression alone was sufficient to up-regulate KLF4, down-regulate E-cadherin and trigger scattering. Chromatin immunoprecipitation (ChIP) analysis further revealed that KLF4 induced suppression of E-cadherin transcription by directly binding to the E-cadherin promoter. Additionally, we proved that HGF-induced up-regulation of KLF4 transcription and cell scattering require activation of the MEK/ERK signaling pathway and the induction of early growth response 1 (EGR-1). At the mechanistic level, ChIP analysis validated a direct binding of EGR-1 to the KLF4 promoter for inducing KLF4 transcription; in turn, EGR-1-induced KLF4 binds to its own promoter, thus creating a positive feedback mechanism to sustain KLF4 expression and resultant cell scattering. Collectively, we conclude that KLF4 up-regulation by HGF represents a novel mechanism to mediate HGF-induced cell scattering and perhaps other associated events such as cell migration and invasion.
Limitation of individual folding resources in the ER leads to outcomes distinct from the unfolded protein response
Authors: Eletto Davide , Maganty Avinash , Eletto Daniela , Dersh Devin , Makarewich Catherine , Biswas Chhanda , Paton James C. , Paton Adrienne W. , Doroudgar Shirin , Glembotski Christopher C. , Argon Yair
Published: August 2012

ER stress leads to upregulation of multiple folding and quality control components, known as the unfolded protein response (UPR). Glucose Regulated Proteins 78 and 94 (GRP78/BiP and GRP94) are often upregulated coordinately as part of this homeostatic response. Given that ER chaperones have distinct sets of clients, we asked how cells respond to ablation of individual chaperones. The cellular responses to silencing BiP, GRP94, HSP47, PDIA6 and OS-9, were distinct. When BiP was silenced, a widespread UPR was observed, but when GRP94 was either inhibited or depleted by RNAi, the expression of only some genes, notably BiP and protein disulfide isomerase A6 (PDIA6) was induced. Silencing of HSP47 or OS-9 did not lead to any compensatory induction of other genes. The selective response to GRP94 depletion was distinct from a typical ER stress response, both because other UPR target genes were not affected and because the canonical UPR signaling branches were not activated. The response to silencing of GRP94 did not preclude further UPR induction when chemical stress was imposed. Importantly, re-expression of wild-type GRP94 in the silenced cells prevented the up-regulation of BiP and PDIA6, while re-expression of an ATPase-deficient GRP94 mutant did not, indicating that cells monitor the state of activity of GRP94. These findings suggest that cells are able to distinguish among folding resources and generate distinct responses.
A novel protein complex, mesh-ssk, is required for septate junction formation indrosophilamidgut
Authors: Izumi Yasushi , Yanagihashi Yuichi , Furuse Mikio
Published: August 2012

Septate junctions (SJs) are specialized intercellular junctions that restrict the free diffusion of solutes through the paracellular route in invertebrate epithelia. In arthropods, two morphologically different types of SJs have been reported: pleated SJs and smooth SJs (sSJs), which are found in ectodermally and endodermally derived epithelia, respectively. However, the molecular and functional differences between these SJ types have not been elucidated. Here we report that a novel sSJ-specific component, a single-pass transmembrane protein, termed ‘Mesh’ is highly concentrated in Drosophila sSJs. Compromised mesh expression causes defects in the organization of sSJs, in the localizations of other sSJ proteins, and in the barrier function of the midgut. Ectopic expression of Mesh in cultured cells induces cell-cell adhesion. Mesh forms a complex with Ssk, another sSJ-specific protein, and these proteins are mutually interdependent for their localization. Thus, a novel protein complex comprising Mesh and Ssk plays a significant role in sSJ formation and in intestinal barrier function in Drosophila.
Kinetics and Mechanism for the Scavenging Reaction of the 2,2-Diphenyl-1-picrylhydrazyl Radical by Synthetic Artepillin C Analogues
Authors: Kawashima Tomonori , Manda Sushma , Uto Yoshihiro , Ohkubo Kei , Hori Hitoshi , Matsumoto Ken-ichiro , Fukuhara Kiyoshi , Ikota Nobuo , Fukuzumi Shunichi , Ozawa Toshihiko , Anzai Kazunori , Nakanishi Ikuo
Published: August 2012

The kinetics for the reaction of the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) with artepillin C, a prenylated phenylpropanoid found specifically in Brazilian propolis, and its analogues was examined in deaerated acetonitrile (MeCN) to shed light on the mechanism for the radical-scavenging reaction of phenolic antioxidants as well as on the structure–activity relationship. Among the examined analogues, a compound having a catechol moiety is found to have the largest second-order rate constant (k) for the DPPH•-scavenging reaction. The deuterium kinetic isotope effect of 1.6 was observed for the DPPH•-scavenging reaction of artepillin C in the presence of 0.13 M CD3OD or CH3OH in deaerated MeCN at 298 K. The log k values were found to be linearly correlated with calculated energy difference values (DHT, HT: hydrogen transfer) between the artepillin C analogues and the corresponding phenoxyl radicals, while such a linear correlation cannot be observed between the log k values and calculated ionization potentials (IP), DHT − IP, or experimental one-electron-oxidation potentials of the artepillin C analogues. These results together with a calculated structure of the transition state for the reaction between the artepillin C analogue and DPPH• suggest that the DPPH•-scavenging reaction of the artepillin C analogues in deaerated MeCN proceeds via a one-step hydrogen-atom transfer from the phenolic OH group to DPPH• rather than an electron transfer followed by proton transfer.
Crystalline Polymorphs and Successive Phase Transitions of Mesogenic 6-Octyloxy-2-naphthyl 4-Octylbenzoate
Authors: Hori Kayako , Ouchi Hanako
Published: August 2012

The title compound has two crystal forms I and II mediated by CH–π interactions at room temperature. Molecular long axes are parallel in I while crossed in II. On cooling, II transforms to three metastable forms with similar structures to II.
Safety and efficacy of splenic artery coil embolization for hypersplenism in liver cirrhosis
Authors: Gu Jian-Jian , He Xin-Hong , Li Wen-Tao , Ji Jun , Peng Wei-Jun , Li Guo-Dong , Wang Sheng-Ping , Xu Li-Chao
Published: August 2012

Background

Partial splenic artery embolization is an effective treatment for hypersplenism but often lacks long-term benefits.

Purpose

To evaluate the long-term effects of coil embolization of the splenic artery in patients with liver cirrhosis and hypersplenism.

Material and Methods

Forty-nine patients with liver cirrhosis and hypersplenism underwent coil embolization of the main splenic artery. The coils were deployed in the mid- or distal segment of the splenic artery to allow collateral blood flow to the spleen. The following data were collected from 2 weeks to 4 years after the embolization: technical success, length of hospital stay, white blood cell count, platelet count, splenic volume, and complication.

Results

The technical success rate of splenic artery coil embolization was 100%. The post embolization syndrome rate was 75% (36/49) with no incidence of major complications. The mean length of hospital stay was 9 days. After embolization, the patient's white blood and platelet counts increased significantly, peaked at 2 weeks, and gradually decreased during the 4-year follow-up period, but remained at significantly higher levels than pre-embolization levels. Follow-up CT scans demonstrated a gradual increase in the volume of the enhanced portions of the spleens with a decrease in the volume of unenhanced portion. No significant changes occurred in the red blood cell count and liver function after the embolization.

Conclusion

Embolization of the mid-and distal main splenic artery with coils is a safe and effective treatment of hypersplenism in cirrhosis with long-term hematologic benefits.
Can segmented 3D images be used for stenosis evaluation in coronary CT angiography?
Authors: Wang Chunliang , Persson Anders , Engvall Jan , De Geer Jakob , Czekierda Waldemar , Björkholm Anders , Fransson Sven-Göran , Smedby Örjan
Published: August 2012

Background

Thanks to the development of computed tomography (CT) scanners and computer software, accurate coronary artery segmentation can be achieved with minimum user interaction. However, the question remains whether we can use these segmented images for reliable diagnosis.

Purpose

To retrospectively evaluate the diagnostic accuracy of coronary CT angiography (CCTA) using segmented 3D data for the detection of significant stenosis.

Material and Methods

CCTA data-sets from 30 patients were acquired with a 64-slice CT scanner and segmented using the region growing (RG) method and the “virtual contrast injection” (VC) method. Three types of images of each patient were reviewed by different reviewers for the presence of stenosis with diameter reduction of 50% or more. The evaluation was performed on four main arteries of each patient (120 arteries in total). For the original series, the reviewer was allowed to use all the 2D and 3D visualization tools available (conventional method). For the segmented results from RG and VC, only maximum intensity projection was used. Evaluation results were compared with catheter angiography (CA) for each artery in a blinded fashion.

Results

Overall, 34 arteries with significant stenosis were identified by CA. The percentage of evaluable arteries, accuracy and negative predictive value for detecting stenosis were, respectively, 86%, 74%, and 93% for the conventional method, 83%, 71%, and 92% for VC, and 64%, 56%, and 93% for RG. Accuracy was significantly lower for the RG method than for the other two methods ( P < 0.01), whereas there was no significant difference in accuracy between the VC method and the conventional method ( P = 0.22).

Conclusion

The diagnostic accuracy for the RG-segmented 3D data is lower than those with access to 2D images, whereas the VC method shows diagnostic accuracy similar to the conventional method.
The effectiveness of erythromycin in reducing stent-related tissue hyperplasia: an experimental study with a rat esophageal model
Authors: Kim Eun-Young , Park Yang Shin , Shin Ji Hoon , Cho Young Jun , Shin Dong-Ho , Yoon Hyun-Ki , Song Ho-Young
Published: August 2012

Background

Erythromycin is not only a potent antibiotic; it also has effects of reduction of inflammation and suppression of protein synthesis.

Purpose

To evaluate the impact of erythromycin on tissue hyperplasia after stent placement in a rat esophageal model.

Material and Methods

A total of 21 rats were included. After placement of self-expanding stents in the mid esophagus, the rats were divided into two experimental groups and one control group. The rats in the experimental groups received daily intraperitoneal injections of erythromycin for 5 weeks; 4 mg/kg (group A, n = 7) and 8 mg/kg (group B, n = 7). Those in the control group ( n = 7) received 1 mL of saline intraperitoneally. After sacrifice, histologic analysis was done for thickness of the papillary projection, granulation tissue area, percentage of granulation tissue area, and degree of inflammatory cell infiltration. The statistical significance of differences between groups was assessed by Mann-Whitney U test.

Results

Tissue hyperplasia as reflected in thickness of papillary projection, granulation tissue area, and percentage of granulation tissue area, was higher in the control group than in the experimental groups, although there was no statistical significance ( P = 1.00, 0.332, and 0.263, respectively). However, degree of inflammatory cell infiltration was significantly lower in the experimental groups than the control group ( P = 0.025), and the higher dosage of erythromycin reduced inflammatory cell infiltration significantly ( P = 0.037).

Conclusion

Intraperitoneal administration of erythromycin is very effective in reducing inflammation after stent placement in a rat esophageal model but has no significant effect on granulation tissue formation.
Knowledge of Clostridium difficile infection among UK health-care workers: development of a knowledge assessment tool
Authors: Brady R R W , Rodrigues M A , Harrison R , Rae C , Graham C , Poxton I R , Gibb A P
Published: August 2012

Doctors’ knowledge provides the basis to support good practice in infection prevention and control. However, there exists a paucity of validated knowledge assessment tools that can be reliably employed to identify poor knowledge levels of Clostridium difficile infection (CDI) within populations of doctors, preventing the effective identification of knowledge deficiencies and focused targeting of educational interventions. Here, we describe a development process to validate a novel CDI knowledge assessment tool for doctors. Two previously published CDI knowledge questionnaires were amalgamated to produce a combined questionnaire. Content was further evaluated by a panel of CDI experts, producing the ‘Lothian’ questionnaire. These questionnaires were tested in control populations comprising either infection control nurse (ICN) specialists or non-clinically trained individuals, and a cohort of medical staff. We compared the efficacy of the ‘Lothian’ questionnaire against that of previous questionnaire reports. We found that all of the questionnaires studied significantly discriminated between non-clinical and clinical populations (ICNs and medical staff) ( P < 0.001) and had similar levels of sensitivity and specificity in discrimination between these targeted populations. This study describes the development of a robust CDI knowledge assessment tool that can be used to evaluate knowledge levels among doctors, compare populations and assist the targeting of educational interventions and plot trends following such interventions.
Accuracy of minimal-preparation computerized tomography in the investigation of suspected colorectal cancer in frail patients: the experience of Western General Hospital, Edinburgh
Authors: Wong L F , Glancy S
Published: August 2012

Traditional methods of investigating suspected colorectal carcinoma (CRC) such as barium enema, colonoscopy and computerized tomography (CT) pneumocolon are often poorly tolerated by frail or elderly patients. Comparatively, minimal-preparation CT (MPCT) is a non-invasive investigation that does not require bowel preparation. The aim of this study was to review MPCTs carried out at the Western General Hospital, Edinburgh, and compare findings with current published data. Retrospective analysis of 85 patients (age range 55–99 years) who underwent MPCTs at the Western General Hospital between May 2005 and June 2008 was undertaken. Results were followed up using clinical notes, pathological and surgical databases. Subsequent outcomes were analysed (average follow-up 22 months). The prevalence of CRC within the study cohort was 0.14. Sensitivity of MPCT was 1 (95% confidence interval [CI], 0.69–1) with a specificity of 0.93 (95% CI, 0.84–0.97). Thirty percent of patients were found to have extracolonic findings requiring further investigation or intervention. Of the patients, 4.7% had an extracolonic malignancy diagnosed on MPCT. MPCT is a sensitive and specific method of investigating CRC in the elderly, infirm or immobile. Our results were found to be comparable with that of current published data, validating the service provided at the Western General Hospital.
Paediatric forearm fractures in the west of Scotland
Authors: Bell S W , Mclaughlin D , Huntley J S
Published: August 2012

Forearm fractures are common paediatric injuries. This study aimed to describe the epidemiology and treatment of paediatric forearm fractures in the urban population of Glasgow. We reviewed all forearm fractures treated by the orthopaedic service in Yorkhill Children's Hospital in 2008 up to the age of 13 years. Data were gathered from case-notes and radiographs using the prospective orthopaedic database to identify patients with forearm fractures. The age, sex, side and type of fracture, the timing and mechanism of the injury and treatment were documented for the 439 fractures. Census data were used to derive absolute age-specific incidences. Distinction was made between torus and other types of fractures. Torus fractures require no specific orthopaedic treatment and were segregated out. For the remaining 314 fractures, the age and sex distribution, seasonal variation of fractures and treatments for each type of fracture were examined. The incidence of forearm fractures in our population is 411 fractures per 100,000 population per year and 294 fractures per 100,000 population per year for non-torus fractures. An increased number of fractures occurred between May and August. A fall from less than 1 m was the most common mechanism of injury. Sporting injuries were the second most common. This study identifies some features which are in agreement with studies from elsewhere in Britain. However, there are also interesting differences, such as the Glasgow peak incidence for forearm fractures being at age eight, with a marked decline by 12 years. Furthermore, our findings have been extended to consideration of type of intervention and likelihood of successful treatment.
Genetic mutations in patients with possible familial hypercholesterolaemia in South East Scotland
Authors: Ho C K M , Stirling D , Hannant W , Walker S W
Published: August 2012

Familial hypercholesterolaemia (FH) is one of the most common genetic disorders in the general population. Genetic testing of this condition is increasingly available in the UK to confirm its diagnosis, but the strategies of genetic testing vary. In this pilot study, we sought to investigate whether a strategy that focuses on the low-density lipoprotein receptor (LDLR) and apolipoprotein B ( APOB) genes can identify the majority of genetic variants in patients with possible FH in South East Scotland. Forty patients with a clinical diagnosis of possible FH according to the Simon Broome criteria were recruited in a lipid clinic serving South East Scotland. All 18 exons of the LDLR gene were sequenced and multiplex ligation probe amplification was performed to identify major deletions and duplications. Variants of the APOB gene at codon 3527 were investigated by direct sequencing. Genetic mutations were detected in 45% of the patients. Sixteen patients (40%) were found to have mutations in their LDLR gene, whereas two other patients (5%) were identified as heterozygous for the APOB variant commonly associated with FH (c.10580G>A; p.R3527Q). None of these genetic variants were detected in more than two patients. Multiple genetic mutations are associated with a clinical phenotype of FH in South East Scotland. A genetic testing strategy which focuses on a limited number of mutations is unlikely to confirm the diagnosis of FH in the majority of patients in this part of Scotland.
Paediatric head injury admissions over a 10-year period in a regional neurosurgical unit
Authors: Phang I , Mathieson C , Sexton I , Forsyth S , Brown J , George E J St
Published: August 2012

Traumatic brain injury is a leading cause of death and disability in childhood. A retrospective study of all paediatric head injuries admitted to the neurosurgical unit for the West of Scotland over a 10-year period was performed to assess the impact of the National Institute for Health and Clinical Excellence head injury guidelines on the admission rate and to determine the associated risk factors, causes, severity and outcomes of these injuries. There were 564 admissions between 1998 and 2007. The median age at presentation was nine years and two months. There was no change in the admission rate, injury mechanism or severity of head injury admitted over the period studied. A relationship was observed between the Scottish Index of Multiple Deprivation Score and the incidence of head injury ( P = 0.05). Alcohol was reported as a causative factor in only a small number of cases, and moderate to severe head injuries were more commonly identified as a result of road traffic accidents.
Axitinib and Vismodegib
Authors: Waddell Aubrey , Solimando Dominic A.
Published: August 2012

The complexity of cancer chemotherapy requires pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparation, dispensing, and administration of antineoplastic therapy, and the agents, both commercially available and investigational, used to treat malignant diseases.
Ondansetron: Rosacea
Authors: Generali Joyce A. , Cada Dennis J.
Published: August 2012

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to jgeneral@kumc.edu .
The Complexity and Importance of Residency Precepting: A Series Introduction
Authors: Buck Brian , Wilkinson Samaneh , Phillips Holly
Published: August 2012

Preceptor development is an area of significant challenge facing residency leadership and preceptors across the nation. This series will focus on establishing a foundation necessary for successful precepting in today's fast-paced profession. Through discussion and presentation of these materials, preceptors should be able to enhance current precepting skills and identify ways to improve preceptor development programs at their practice sites. The series will review current preceptor development programs and provide options for programs that may be struggling with where to start with preceptor development. Key topics covered will include characteristics of good precepting, generational needs, effective feedback, development of a preceptor program, and finally comparison of resident and student learning needs.