bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the absolute renal risk of dialysis/death in adults with IgA nephropathy secondary to Henoch-Schönlein purpura: a monocentric cohort study
Authors: Mohey Hesham , Laurent Blandine , Mariat Christophe , Berthoux Francois 
Published: August 2013

Abstract

Background
We established earlier the absolute renal risk (ARR) of dialysis/death (D/D) in primary IgA nephropathy (IgAN) which permitted accurate prospective prediction of final prognosis. This ARR was based on the potential presence at initial diagnosis of three major, independent, and equipotent risk factors such as hypertension, quantitative proteinuria ≥ 1 g per day, and severe pathological lesions appreciated by our local classification scoring ≥ 8 (range 0–20). We studied the validity of this ARR concept in secondary IgAN to predict future outcome and focused on Henoch-Schönlein purpura (HSP) nephritis.

Methods
Our cohort of adults IgAN concerned 1064 patients with 101 secondary IgAN and was focused on 74 HSP (59 men) with a mean age of 38.6 at initial diagnosis and a mean follow-up of 11.8 years. Three major risk factors: hypertension, proteinuria ≥1 g/d, and severe pathological lesions appreciated by our global optical score ≥8 (GOS integrated all elementary histological lesions), were studied at biopsy-proven diagnosis and their presence defined the ARR scoring: 0 for none present, 3 for all present, 1 or 2 for the presence of any 1 or 2 risk factors. The primary end-point was composite with occurrence of dialysis or death before (D/D). We used classical statistics and both time-dependent Cox regression and Kaplan-Meier survival curve methods.

Results
The cumulative rate of D/D at 10 and 20 years post-onset was respectively 0 and 14% for ARR = 0 (23 patients); 10 and 23% for ARR = 1 (N = 19); 27 and 33% for ARR = 2 (N = 24); and 81 and 100% (before 20 y) in the 8 patients with ARR = 3 (P = 0.0007). Prediction at time of diagnosis (time zero) of 10y cumulative rate of D/D event was 0% for ARR = 0, 10% for ARR = 1, 33% for ARR = 2, and 100% by 8.5y for ARR = 3 (P = 0.0003) in this adequately treated cohort.

Conclusion
This study clearly validates the Absolute Renal Risk of Dialysis/Death concept in a new cohort of HSP-IgAN with utility to individual management and in future clinical trials.
Study protocol of Prednisone in episodic Cluster Headache (PredCH): a randomized, double-blind, placebo-controlled parallel group trial to evaluate the efficacy and safety of oral prednisone as an add-on therapy in the prophylactic treatment of episodic cluster headache with verapamil
Authors: Holle Dagny , Burmeister Jan , Scherag André , Ose Claudia , Diener Hans-Christoph , Obermann Mark 
Published: July 2013

Abstract

Background
Episodic cluster headache (ECH) is a primary headache disorder that severely impairs patient’s quality of life. First-line therapy in the initiation of a prophylactic treatment is verapamil. Due to its delayed onset of efficacy and the necessary slow titration of dosage for tolerability reasons prednisone is frequently added by clinicians to the initial prophylactic treatment of a cluster episode. This treatment strategy is thought to effectively reduce the number and intensity of cluster attacks in the beginning of a cluster episode (before verapamil is effective). This study will assess the efficacy and safety of oral prednisone as an add-on therapy to verapamil and compare it to a monotherapy with verapamil in the initial prophylactic treatment of a cluster episode.

Methods and design
PredCH is a prospective, randomized, double-blind, placebo-controlled trial with parallel study arms. Eligible patients with episodic cluster headache will be randomized to a treatment intervention with prednisone or a placebo arm. The multi-center trial will be conducted in eight German headache clinics that specialize in the treatment of ECH.

Discussion
PredCH is designed to assess whether oral prednisone added to first-line agent verapamil helps reduce the number and intensity of cluster attacks in the beginning of a cluster episode as compared to monotherapy with verapamil.

Trial registration
German Clinical Trials Register DRKS00004716
Neutral sphingomyelinase 2 modulates cytotoxic effects of protopanaxadiol on different human cancer cells
Authors: Park Bonggoo , Lee Yong-Moon , Kim Jae-Sung , Her Youl , Kang Ju Hee , Oh Seung-Hyun , Kim Hwan-Mook 
Published: July 2013

Abstract

Background
Some of ginsenosides, root extracts from Panax ginseng, exert cytotoxicity against cancer cells through disruption of membrane subdomains called lipid rafts. Protopanaxadiol (PPD) exhibits the highest cytotoxic effect among 8 ginsenosides which we evaluated for anti-cancer activity. We investigated if PPD disrupts lipid rafts in its cytotoxic effects and also the possible mechanisms.

Methods
Eight ginsenosides were evaluated using different cancer cells and cell viability assays. The potent ginsenoside, PPD was investigated for its roles in lipid raft disruption and downstream pathways to apoptosis of cancer cells. Anti-cancer effects of PPD was also investigated in vivo using mouse xenograft model.

Results
PPD consistently exerts its potent cytotoxicity in 2 cell survival assays using 5 different cancer cell lines. PPD disrupts lipid rafts in different ways from methyl-β-cyclodextrin (MβCD) depleting cholesterol out of the subdomains, since lipid raft proteins were differentially modulated by the saponin. During disruption of lipid rafts, PPD activated neutral sphingomyelinase 2 (nSMase 2) hydrolyzing membrane sphingomyelins into pro-apoptotic intracellular ceramides. Furthermore, PPD demonstrated its anti-cancer activities against K562 tumor cells in mouse xenograft model, confirming its potential as an adjunct or chemotherapeutic agent by itself in vivo.

Conclusions
This study demonstrates that neutral sphingomyelinase 2 is responsible for the cytotoxicity of PPD through production of apoptotic ceramides from membrane sphingomyelins. Thus neutral sphingomyelinase 2 and its relevant mechanisms may potentially be employed in cancer chemotherapies.
Spermicidal and anti-Trichomonas vaginalis activity of Brazilian Sapindus saponaria
Authors: Damke Edilson , Tsuzuki Joyce K , Chassot Francieli , Cortez Diógenes AG , Ferreira Izabel CP , Mesquita Cristiane SS , da-Silva Vânia RS , Svidzinski Terezinha IE , Consolaro Márcia EL 
Published: July 2013

Abstract

Background

Sapindus saponaria is used traditionally for curing ulcers, external wounds and inflammations. The spermicidal and anti-Trichomonas activity of S. saponaria and its effect on Lactobacillus acidophilus were evaluated.

Methods
Water-ethanol (WE) and butanolic (BE) extracts, as well as a purified sample of saponins (SP) from S. saponaria were tested for spermicidal and anti-Trichomonas activity and for their effect on L. acidophilus.

Results
WE, BE and SP immobilized spermatozoa at a minimum effective concentration (MEC) of 2.5 (gram %) for extracts and 1.25 (gram %) for SP. The effective concentrations that caused 50% immobilization of spermatozoa (EC50) were 0.5 (gram %) for WE and SP, and 0.1 (gram %) for BE. The compounds were effective against Trichomonas vaginalis (Minimum Inhibitory Concentration = 0.156 mg/mL for WE and BE, and 0.078 mg/mL for SP against a clinical strain (CS); and 0.312, 0.156 and 0.078 mg/mL for WE, BE and SP, respectively, against an ATCC strain). In all concentrations tested, the growth of L. acidophilus was not reduced.

Conclusion
The in vitro study proved the spermicidal and anti-Trichomonas activity of S. saponaria. Complementary in vivo studies should be made for establish the use as a vaginal spermicide, particularly in Brazil and Latin America.
Characterizing the normal proteome of human ciliary body
Authors: Goel Renu , Murthy Krishna R , Srikanth Srinivas M , Pinto Sneha M , Bhattacharjee Mitali , Kelkar Dhanashree S , Madugundu Anil K , Dey Gourav , Mohan Sujatha S , Krishna Venkatarangaiah , Prasad TS Keshava , Chakravarti Shukti , Harsha HC , Pandey Akhilesh 
Published: August 2013

Abstract

Background
The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body.

Results
In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

Conclusions
More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia.
HIV-1 Nef promotes the localization of Gag to the cell membrane and facilitates viral cell-to-cell transfer
Authors: Malbec Marine , Sourisseau Marion , Guivel-Benhassine Florence , Porrot Françoise , Blanchet Fabien , Schwartz Olivier , Casartelli Nicoletta 
Published: July 2013

Abstract

Background
Newly synthesized HIV-1 particles assemble at the plasma membrane of infected cells, before being released as free virions or being transferred through direct cell-to-cell contacts to neighboring cells. Localization of HIV-1 Gag precursor at the cell membrane is necessary and sufficient to trigger viral assembly, whereas the GagPol precursor is additionally required to generate a fully matured virion. HIV-1 Nef is an accessory protein that optimizes viral replication through partly defined mechanisms. Whether Nef modulates Gag and/or GagPol localization and assembly at the membrane and facilitates viral cell-to-cell transfer has not been extensively characterized so far.

Results
We report that Nef increases the total amount of Gag proteins present in infected cells, and promotes Gag localization at the cell membrane. Moreover, the processing of p55 into p24 is improved in the presence of Nef. We also examined the effect of Nef during HIV-1 cell-to-cell transfer. We show that without Nef, viral transfer through direct contacts between infected cells and target cells is impaired. With a nef-deleted virus, the number of HIV-1 positive target cells after a short 2h co-culture is reduced, and viral material transferred to uninfected cells is less matured. At later time points, this defect is associated with a reduction in the productive infection of new target cells.

Conclusions
Our results highlight a previously unappreciated role of Nef during the viral replication cycle. Nef promotes HIV-1 Gag membrane localization and processing, and facilitates viral cell-to-cell transfer.
Urinary 2,5-hexanedione excretion in cryptogenic polyneuropathy compared to the general Swedish population
Authors: Persson Bodil , Vrethem Magnus , Murgia Nicola , Lindh Jonas , Hällsten Anna-Lena , Fredrikson Mats , Tondel Martin 
Published: July 2013

Abstract

Background
2,5-hexanedione (2,5-HD) is the main neurotoxic metabolite of methyl-n-butyl ketone (MBK) and n-hexane, and known to cause polyneuropathy. The aim of our study was to compare the urinary levels of 2,5-HD between cases with cryptogenic polyneuropathy and the general Swedish population, and to elucidate the role of certain external factors.

Methods
Morning urine samples were collected from 114 cases with cryptogenic polyneuropathy (77 men and 37 women) and 227 referents (110 men and 117 women) randomly selected from the population registry. None had any current occupational exposure to n-hexane or MBK. The urine samples were analysed by a gas chromatographic method based on acidic hydrolysis.

Results
Cases had statistically higher urinary levels of 2,5-HD (0.48 mg/L) than the general population (0.41 mg/L) and men higher excretion than women (0.48 mg/L and 0.38 mg/L, respectively). There was no difference in 2,5-HD levels between current smokers and non-smokers. Occupational exposure to xylene, alcohol consumption and ever exposed to general anaesthesia were associated with lower excretion in men while for occupational exposure to nitrous oxide in women higher excretion was seen. Higher excretion of 2,5 HD was inversely related to increasing age.

Conclusions
Significantly higher levels of urinary 2,5-HD were seen in men and cryptogenic polyneuropathy cases seemingly unexposed to n-hexane. Hypothetically, this might be due to either differences in metabolic patterns or some concealed exposure. The difference in means between cases and the general population is small and can therefore not allow any firm conclusions of the causality, however.
The production and characterization of a new active lipase from Acremonium alcalophilum using a plant bioreactor
Authors: Pereira Eridan Orlando , Tsang Adrian , McAllister Tim A , Menassa Rima 
Published: August 2013

Abstract

Background
Microorganisms are the most proficient decomposers in nature, using secreted enzymes in the hydrolysis of lignocellulose. As such, they present the most abundant source for discovery of new enzymes. Acremonium alcalophilum is the only known cellulolytic fungus that thrives in alkaline conditions and can be cultured readily in the laboratory. Its optimal conditions for growth are 30°C and pH 9.0-9.2. The genome sequence of Acremonium alcalophilum has revealed a large number of genes encoding biomass-degrading enzymes. Among these enzymes, lipases are interesting because of several industrial applications including biofuels, detergent, food processing and textile industries.

Results
We identified a lipA gene in the genome sequence of Acremonium alcalophilum, encoding a protein with a predicted lipase domain with weak sequence identity to characterized enzymes. Unusually, the predicted lipase displays ≈ 30% amino acid sequence identity to both feruloyl esterase and lipase of Aspergillus niger. LipA, when transiently produced in Nicotiana benthamiana, accumulated to over 9% of total soluble protein. Plant-produced recombinant LipA is active towards p-nitrophenol esters of various carbon chain lengths with peak activity on medium-chain fatty acid (C8). The enzyme is also highly active on xylose tetra-acetate and oat spelt xylan. These results suggests that LipA is a novel lipolytic enzyme that possesses both lipase and acetylxylan esterase activity. We determined that LipA is a glycoprotein with pH and temperature optima at 8.0 and 40°C, respectively.

Conclusion
Besides being the first heterologous expression and characterization of a gene coding for a lipase from A. alcalophilum, this report shows that LipA is very versatile exhibiting both acetylxylan esterase and lipase activities potentially useful for diverse industry sectors, and that tobacco is a suitable bioreactor for producing fungal proteins.
Emerging role of cancer stem cells in the biology and treatment of ovarian cancer: basic knowledge and therapeutic possibilities for an innovative approach
Authors: Tomao Federica , Papa Anselmo , Rossi Luigi , Strudel Martina , Vici Patrizia , Lo Russo Giuseppe , Tomao Silverio 
Published: August 2013

AbstractIn 2013 there will be an estimated 22,240 new diagnoses and 14,030 deaths from ovarian cancer in the United States. Despite the improved surgical approach and the novel active drugs that are available today in clinical practice, about 80% of women presenting with late-stage disease have a 5-year survival rate of only 30%. In the last years a growing scientific knowledge about the molecular pathways involved in ovarian carcinogenesis has led to the discovery and evaluation of several novel molecular targeted agents, with the aim to test alternative models of treatment in order to overcome the clinical problem of resistance. Cancer stem cells tend to be more resistant to chemotherapeutic agents and radiation than more differentiated cellular subtypes from the same tissue. In this context the study of ovarian cancer stem cells is taking on an increasingly important strategic role, mostly for the potential therapeutic application in the next future. In our review, we focused our attention on the molecular characteristics of epithelial ovarian cancer stem cells, in particular on possible targets to hit with targeted therapies.
Increased sphingosine-1-phosphate improves muscle regeneration in acutely injured mdx mice
Authors: Ieronimakis Nicholas , Pantoja Mario , Hays Aislinn L , Dosey Timothy L , Qi Junlin , Fischer Karin A , Hoofnagle Andrew N , Sadilek Martin , Chamberlain Jeffrey S , Ruohola-Baker Hannele , Reyes Morayma 
Published: August 2013

Abstract

Background
Presently, there is no effective treatment for the lethal muscle wasting disease Duchenne muscular dystrophy (DMD). Here we show that increased sphingosine-1-phoshate (S1P) through direct injection or via the administration of the small molecule 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor, has beneficial effects in acutely injured dystrophic muscles of mdx mice.

Methods
We treated mdx mice with and without acute injury and characterized the histopathological and functional effects of increasing S1P levels. We also tested exogenous and direct administration of S1P on mdx muscles to examine the molecular pathways under which S1P promotes regeneration in dystrophic muscles.

Results
Short-term treatment with THI significantly increased muscle fiber size and extensor digitorum longus (EDL) muscle specific force in acutely injured mdx limb muscles. In addition, the accumulation of fibrosis and fat deposition, hallmarks of DMD pathology and impaired muscle regeneration, were lower in the injured muscles of THI-treated mdx mice. Furthermore, increased muscle force was observed in uninjured EDL muscles with a longer-term treatment of THI. Such regenerative effects were linked to the response of myogenic cells, since intramuscular injection of S1P increased the number of Myf5

nlacz/+
positive myogenic cells and newly regenerated myofibers in injured mdx muscles. Intramuscular injection of biotinylated-S1P localized to muscle fibers, including newly regenerated fibers, which also stained positive for S1P receptor 1 (S1PR1). Importantly, plasma membrane and perinuclear localization of phosphorylated S1PR1 was observed in regenerating muscle fibers of mdx muscles. Intramuscular increases of S1P levels, S1PR1 and phosphorylated ribosomal protein S6 (P-rpS6), and elevated EDL muscle specific force, suggest S1P promoted the upregulation of anabolic pathways that mediate skeletal muscle mass and function.

Conclusions
These data show that S1P is beneficial for muscle regeneration and functional gain in dystrophic mice, and that THI, or other pharmacological agents that raise S1P levels systemically, may be developed into an effective treatment for improving muscle function and reducing the pathology of DMD.
Mercurial-resistance determinants in Pseudomonas strain K-62 plasmid pMR68
Authors: Sone Yuka , Mochizuki Yusuke , Koizawa Keita , Nakamura Ryosuke , Pan-Hou Hidemitsu , Itoh Tomoo , Kiyono Masako 
Published: July 2013

Abstract
We report the complete nucleotide sequence of plasmid pMR68, isolated from Pseudomonas strain K-62, two plasmids contribute to broad-spectrum mercury resistance and that the mer operon from one of them (pMR26) has been previously characterized. The plasmid was 71,020 bp in length and contained 75 coding regions. Three mer gene clusters were identified. The first comprised merR-orf4-orf5-merT1-merP1-merF-merA-merB1, which confers bacterial resistance to mercuric ions and organomercury. The second and third clusters comprised merT2-merP2, which encodes a mercury transport system, and merB2, which encodes an organomercurial lyase, respectively. The deduced amino acid sequences for the proteins encoded by each of the mer genes identified in pMR68 bore greater similarity to sequences from Methylobacterium extorquens AM1 than to those from pMR26, a second mercury-resistance plasmid from Pseudomonas strain K-62. Escherichia coli cells carrying pMKY12 (containing merR-orf4-orf5-merT1-merP1-merF-merA-merB1 cloned from pMR68) and cells carrying pMRA114 (containing merR-merT-merP-merA-merG-merB1 cloned from plasmid pMR26) were more resistant to, and volatilized more, mercury from mercuric ions and phenylmercury than the control cells. The present results, together with our earlier findings, indicate that the high phenylmercury resistance noted for Pseudomonas strain K-62 seems to be achieved by multiple genes, particularly by the multiple merB encoding organomercurial lyase and one merG encoding cellular permeability to phenylmercury. The novel mer gene identified in pMR68 may help us to design new strategies aimed at the bioremediation of mercurials.
Energy intake, nutritional status and weight reduction in patients one year after laparoscopic sleeve gastrectomy
Authors: Gjessing Hanne Rosendahl , Nielsen Hans Jørgen , Mellgren Gunnar , Gudbrandsen Oddrun Anita 
Published: July 2013

Abstract

Background
Laparoscopic sleeve gastrectomy (LSG) is increasingly popular due to its efficiency in reducing excess weight, however little is known about the nutritional status in patients after surgery.

Purpose
To investigate how LSG affects energy intake, nutritional status and body weight one year after surgery.

Methods
A total of 150 patients (116 women) were enrolled in the study. Data on body weight, waist circumference and blood samples were registered preoperatively and after surgery. Food intake was reported 3 and 12 months postoperatively.

Results
The preoperative median BMI was 44.3 (inter quartile range 41.4-47.1), and was significantly reduced to 35.4 (32.6-38.6) after 3 months and further reduced to 30.5 (27.4-33.8) 12 months after surgery (p < 0.05). The median post surgery daily energy intake was significantly increased from 2971 (1982–3687) kJ after three months to 3840 (3046–4625) kJ twelve months postoperatively. One year after surgery, serum levels of folate, cobalamin, PTH and HDL cholesterol were significantly increased, whereas calcium, albumin, haemoglobin, creatinine, uric acid, CRP, glucose, insulin, insulin c-peptide, HOMA-IR, HbA1c and triacylglycerol were significantly decreased. Serum levels of vitamins E and D were unchanged after one year. The prevalence of patients with medically regulated type 2 diabetes was significantly reduced one year post surgery however no changes were seen in the prevalence of patients taking lipid lowering drugs or thyroxin.

Conclusion
Based on the data obtained 12 months after surgery, LSG appears to be an effective treatment of morbid obesity without worsening the nutritional status despite the very low energy intake.