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[PMID]: 23030413 [Au] Autor: Tashtoush BM; Bennamani AN; Al-Taani BM [Ad] Address: Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology , P.O. Box 3030, Irbid 22110 , Jordan. [Ti] Title: Preparation and characterization of microemulsion formulations of nicotinic acid and its prodrugs for transdermal delivery. [So] Source: Pharm Dev Technol;18(4):834-43, 2013 Jul-Aug. [Is] ISSN: 1097-9867 [Cp] Country of publication: England [La] Language: eng [Ab] Abstract: At pharmacological doses, nicotinic acid has a lipid-regulating effect and is in use clinically for that purpose. However, despite of all features, its utility is strongly limited by several disadvantages such as, extensive hepatic metabolism and flushing. Transdermal delivery of nicotinic acid may, therefore, be the solution to reducing side effects associated with oral administration, and to maintaining constant therapeutic blood levels for longer duration. The aim of this investigation was to develop a suitable formulation or select a suitable vehicle for the transdermal delivery of highly lipophilic prodrugs of nicotinic acid (dodecyl and myristyl nicotinate) designed to deliver nicotinic acid through skin without causing vasodilatation and flushing and optimizing its delivery to the blood stream. A microemulsion system and penetration enhancers have been attempted in this study. The microemulsion system was composed of isopropyl myristate (IPM), water and a 4:1 (w/w) mixture of Labrasol and Peceol where a pseudoternary phase diagram was constructed. Furthermore, the microemulsion formulations with different component ratios were characterized by determination of conductivity, pH, particle size, viscosity and refractive index. According to the particle size analysis, conductivity and viscosity measurements, the microemulsion formulations that formed were of oil-in-water type. The transdermal permeability of nicotinic acid and its prodrugs was evaluated in vitro using Franz diffusion cells fitted with mice skin and nicotinic acid concentration was analyzed by high performance liquid chromatography. A theoretical design of percutaneous penetration optimization in which prodrugs derivation and enhancer application are combined based on the skin diffusion model was experimentally verified. The selected formulations seemed promising for developing a transdermal drug delivery system of nicotinic acid from dodecyl nicotinate that would offer advantages like possible controlled drug release, reduced flushing, increased drug stability and ease of large-scale production. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.3109/10837450.2012.727003

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[PMID]: 23671416 [Au] Autor: Yukl SA; Boritz E; Busch M; Bentsen C; Chun TW; Douek D; Eisele E; Haase A; Ho YC; Hütter G; Justement JS; Keating S; Lee TH; Li P; Murray D; Palmer S; Pilcher C; Pillai S; Price RW; Rothenberger M; Schacker T; Siliciano J; Siliciano R; Sinclair E; Strain M; Wong J; Richman D; Deeks SG [Ad] Address: San Francisco VA Medical Center (SFVA) and University of California, San Francisco (UCSF), San Francisco, California, United States of America. [Ti] Title: Challenges in Detecting HIV Persistence during Potentially Curative Interventions: A Study of the Berlin Patient. [So] Source: PLoS Pathog;9(5):e1003347, 2013 May. [Is] ISSN: 1553-7374 [Cp] Country of publication: United States [La] Language: eng [Ab] Abstract: There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1371/journal.ppat.1003347

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[PMID]: 23671673 [Au] Autor: Downer EJ; Jones RS; McDonald CL; Greco E; Brennan S; Connor TJ; Robertson IH; Lynch MA [Ad] Address: Trinity College Institute of Neuroscience and Physiology Department, Trinity College, Dublin, Ireland. [Ti] Title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory. [So] Source: PLoS One;8(5):e63194, 2013. [Is] ISSN: 1932-6203 [Cp] Country of publication: United States [La] Language: eng [Ab] Abstract: BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1371/journal.pone.0063194

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[PMID]: 23671585 [Au] Autor: Nordgård O; Singh G; Solberg S; Jørgensen L; Halvorsen AR; Smaaland R; Brustugun OT; Helland A [Ad] Address: Department of Hematology and Oncology, Stavanger University Hospital, Stavanger, Norway. [Ti] Title: Novel molecular tumor cell markers in regional lymph nodes and blood samples from patients undergoing surgery for non-small cell lung cancer. [So] Source: PLoS One;8(5):e62153, 2013. [Is] ISSN: 1932-6203 [Cp] Country of publication: United States [La] Language: eng [Ab] Abstract: INTRODUCTION: Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC). METHODS: Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data. RESULTS: All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004). CONCLUSIONS: Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1371/journal.pone.0062153

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[PMID]: 23671392 [Au] Autor: Zhang ZM; Yang XM; Zhang C; Zhang MJ; Li X; Zhang FH; Kang S; Wang SJ; Shan BE [Ad] Address: Department of Gynecology and Obstetrics, Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China. [Ti] Title: Antitumor effects and mechanisms of dendritic cells stimulated by sCD40L on ovarian cancer cells in vitro. [So] Source: Onco Targets Ther;6:503-15, 2013. [Is] ISSN: 1178-6930 [Cp] Country of publication: New Zealand [La] Language: eng [Ab] Abstract: OBJECTIVE: This study aimed to examine the expression of immune suppression factors and the mechanisms of antitumor effects of cord blood dendritic cells (DCs) stimulated by soluble cluster of differentiation 40 ligand (sCD40L) and cytokines in vitro in ovarian cancer patients. METHODS: The expression levels of interleukin (IL)-10 and transforming growth factor (TGF)-ß messenger RNA in peripheral blood were detected by reverse transcription polymerase chain reaction; expression levels of CD80 and CD86 in DCs stimulated by sCD40L were detected using flow cytometry and confocal laser scanning microscopy. RESULTS: Expression levels of IL-10 and TGF-ß genes in the peripheral blood of ovarian cancer patients were significantly increased compared with patients with benign ovarian tumors (P < 0.05). The expression levels of CD80 and CD86 in DCs cultured in the granulocyte-macrophage colony-stimulating factor + IL-4 + stem cell factor + Flt-3 ligand + sCD40L group were significantly increased compared with those in the control group, as assessed by flow cytometry and confocal laser scanning microscopy (P < 0.05). CONCLUSION: A variety of cytokines in combination with sCD40L can promote the proliferation of cord blood-derived DCs and induce their maturation as well as stimulating a specific antitumor response. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [St] Status: In-Data-Review [do] DOI: 10.2147/OTT.S40504

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[PMID]: 23471675 [Au] Autor: Moon R; Teixeira A; Varnadore S; Potenza K; Jawad MA [Ad] Address: Department of Bariatric Surgery, Orlando Regional Medical Center, Bariatric and Laparoscopy Center, Orlando Health, 89 Copeland Dr, 1st Floor, Orlando, FL, 32806, USA. [Ti] Title: Reinforcing the Staple Line with Surgicel® Nu-knit® in Roux-en-Y Gastric Bypass: Comparison with Bovine Pericardial Strips. [So] Source: Obes Surg;23(6):788-93, 2013 Jun. [Is] ISSN: 1708-0428 [Cp] Country of publication: United States [La] Language: eng [Ab] Abstract: BACKGROUND: In the literature, staple line leak rate is reported to be 1-6 %, and hemorrhage rate is 2-5 % in laparoscopic Roux-en-Y gastric bypass (LRYGB). Various buttress materials are available in an attempt to reduce perioperative complications. The aims of our study are to evaluate the effect of using absorbable hemostat (SNK) as buttress material and compare its usage with bovine pericardial strips (PSD). METHODS: Between January 2006 to May 2007 and from October 2007 to December 2009, a total of 1,074 patients underwent LRYGB at our institution. Of these 1,074 patients, PSD was used in 443 (41.2 %) patients, and SNK was used in 631 (58.8 %) patients. A retrospective review of a prospectively collected database was performed for all LRYGB patients, noting the outcomes and complications of the procedure. RESULTS: Five (1.1 %) patients required transfusion of packed red blood cells (PRBC) during early postoperative period (postoperative 1-3 days) in the PSD group, while two (0.3 %) patients required transfusion in the SNK group. SNK patients received significantly lower mean units of PRBC (1.0 unit) when compared to that of PSD patients (5.0 units). One (0.2 %) anastomotic leak was found in the PSD group on postoperative day (POD) 10. One (0.2 %) patient in the SNK group also showed an anastomotic leak on POD 2. Additionally, the cost of SNK per procedure was significantly less than that of PSD. CONCLUSIONS: The use of absorbable hemostat as buttress material may be effective in reducing acute postoperative bleeding in LRYGB at a significantly lower cost. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1007/s11695-013-0898-y

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[PMID]: 23668610 [Au] Autor: Damodharan S; Gujar R; Pattabiraman S; Nesakumar M; Hanna LE; Vadakkuppattu RD; Usha R [Ad] Address: Department of Plant Biotechnology, School of Biotechnology, Madurai Kamaraj University, Palkalainagar, Madurai, 625021. [Ti] Title: Expression and immunological characterization of cardamom mosaic virus coat protein displaying HIV gp41 epitopes. [So] Source: Microbiol Immunol;57(5):374-85, 2013 May. [Is] ISSN: 1348-0421 [Cp] Country of publication: Australia [La] Language: eng [Ab] Abstract: The coat protein of cardamom mosaic virus (CdMV), a member of the genus Macluravirus, assembles into virus-like particles when expressed in an Escherichia coli expression system. The N and C-termini of the coat protein were engineered with the Kennedy peptide and the 2F5 and 4E10 epitopes of gp41 of HIV. The chimeric proteins reacted with sera from HIV positive persons and also stimulated secretion of cytokines by peripheral blood mononuclear cells from these persons. Thus, a system based on the coat protein of CdMV can be used to display HIV-1 antigens. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1111/1348-0421.12045

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[PMID]: 23670117 [Au] Autor: Morrison JJ; Ross JD; Dubose JJ; Jansen JO; Midwinter MJ; Rasmussen TE [Ti] Title: Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury: Findings From the MATTERs II Study. [So] Source: JAMA Surg;148(3):218-25, 2013 Mar 1. [Is] ISSN: 2168-6262 [Cp] Country of publication: United States [La] Language: eng [Ab] Abstract: OBJECTIVE To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured. DESIGN Retrospective observational study comparing the mortality of 4 groups: tranexamic acid only, cryoprecipitate only, tranexamic acid and cryoprecipitate, and neither tranexamic acid nor cryoprecipitate. To balance comparisons, propensity scores were developed and added as covariates to logistic regression models predicting mortality. SETTING A Role 3 Combat Surgical Hospital in southern Afghanistan. PATIENTS A total of 1332 patients were identified from prospectively collected UK and US trauma registries who required 1 U or more of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). MAIN OUTCOME MEASURE In-hospital mortality. RESULTS Injury Severity Scores were highest in the cryoprecipitate (mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (mean [SD], 26 [14.9]) groups compared with the tranexamic acid (mean [SD], 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (mean [SD], 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = .01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = .02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < .001), reflecting nonsignificant interaction (P = .21). CONCLUSIONS Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion. Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: AIM; IM [St] Status: In-Data-Review [do] DOI: 10.1001/jamasurg.2013.764

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[PMID]: 22806826 [Au] Autor: Jia Y; Yang Y; Brock MV; Zhan Q; Herman JG; Guo M [Ad] Address: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853, China; Medical College of NanKai University, #94 Weijin Road, Tianjin, 300071, China. [Ti] Title: Epigenetic regulation of DACT2, a key component of the Wnt signalling pathway in human lung cancer. [So] Source: J Pathol;230(2):194-204, 2013 Jun. [Is] ISSN: 1096-9896 [Cp] Country of publication: England [La] Language: eng [Ab] Abstract: Dapper, Dishevelled-associated antagonist of ß-catenin (DACT), is involved in Xenopus embryonic development. Human DACT2 is localized on chromosome 6q27, a region of frequent loss of heterozygosity (LOH) in human cancers. However, the function and regulation of DACT2 in human lung cancer remain unclear. DNA sequencing, methylation-specific PCR (MSP), semi-quantitative RT-PCR, western blotting, and xenograft models were employed in this study. Eight lung cancer cell lines, 106 cases of primary lung cancer, four specimens of normal lung from patients without cancer, and 99 blood samples from healthy individuals were examined. We found that while there was no SNP related to lung cancer, the DACT2 promoter region is frequently methylated in human lung cancer. DACT2 is silenced by promoter region hypermethylation and re-expressed by 5-aza-2'-deoxyazacytidine treatment of lung cancer cell lines. Methylation of DACT2 was associated with poor differentiation of lung cancer. Loss of DACT2 expression was associated with promoter region hypermethylation in primary lung cancer, and was associated with increased ß-catenin expression. Restoration of DACT2 expression suppressed tumour proliferation both in vitro and in vivo. DACT2 expression was down-regulated by siRNA knockdown in H727 cells. DACT2 inhibited T-cell factor/lymphoid enhancer factor (TCF/LEF) and its downstream genes. In conclusion, DACT2 methylation is a potential lung cancer detection marker. DACT2 is regulated by promoter region hypermethylation. DACT2 inhibits lung cancer proliferation by suppressing the Wnt signalling pathway in lung cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [Js] Journal subset: IM [St] Status: In-Data-Review [do] DOI: 10.1002/path.4073

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[PMID]: 23574739 [Au] Autor: Krupa M; Vidal A; Clément F [Ad] Address: Laboratoire Analyse et Probabilités, IBGBI, Université d'Évry-Val-d'Essonne, 23 boulevard de France, 91037, Evry cedex, France. alexandre.vidal@univ-evry.fr. [Ti] Title: A network model of the periodic synchronization process in the dynamics of calcium concentration in GnRH neurons. [So] Source: J Math Neurosci;3(1):4, 2013. [Is] ISSN: 2190-8567 [Cp] Country of publication: Germany [La] Language: eng [Ab] Abstract: Mathematical neuroendocrinology is a branch of mathematical neurosciences that is specifically interested in endocrine neurons, which have the uncommon ability of secreting neurohormones into the blood. One of the most striking features of neuroendocrine networks is their ability to exhibit very slow rhythms of neurosecretion, on the order of one or several hours. A prototypical instance is that of the pulsatile secretion pattern of GnRH (gonadotropin releasing hormone), the master hormone controlling the reproductive function, whose origin remains a puzzle issue since its discovery in the seventies. In this paper, we investigate the question of GnRH neuron synchronization on a mesoscopic scale, and study how synchronized events in calcium dynamics can arise from the average electric activity of individual neurons. We use as reference seminal experiments performed on embryonic GnRH neurons from rhesus monkeys, where calcium imaging series were recorded simultaneously in tens of neurons, and which have clearly shown the occurrence of synchronized calcium peaks associated with GnRH pulses, superposed on asynchronous, yet oscillatory individual background dynamics. We design a network model by coupling 3D individual dynamics of FitzHugh-Nagumo type. Using phase-plane analysis, we constrain the model behavior so that it meets qualitative and quantitative specifications derived from the experiments, including the precise control of the frequency of the synchronization episodes. In particular, we show how the time scales of the model can be tuned to fit the individual and synchronized time scales of the experiments. Finally, we illustrate the ability of the model to reproduce additional experimental observations, such as partial recruitment of cells within the synchronization process or the occurrence of doublets of synchronization. [Pt] Publication type: JOURNAL ARTICLE [Em] Entry month: 1305 [St] Status: In-Data-Review [do] DOI: 10.1186/2190-8567-3-4

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