bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific Reduction of Alcohol’s Motivational Properties by the Positive Allosteric Modulator of the GABAB Receptor, GS39783—Comparison With the Effect of the GABAB Receptor Direct Agonist, Baclofen
Authors: Maccioni Paola , Fantini Noemi , Froestl Wolfgang , Carai Mauro A. M. , Gessa Gian Luigi , Colombo Giancarlo 
Published: July 2008

Background:  Activation of the GABAB receptor—either by means of direct agonists (like baclofen) or positive allosteric modulators (like GS39783)—has been observed to suppress alcohol drinking and reinforcement in rats and mice. The present study was conducted to assess and compare the effect of baclofen and GS39783 on the motivational properties of alcohol.Methods:  Selectively bred Sardinian alcohol‐preferring (sP) rats were initially trained to respond on a lever (on an fixed ratio 4 schedule of reinforcement) to orally self‐administer alcohol (15%, v/v) or sucrose (3%, w/v) in daily 30‐minute sessions. Once lever‐responding reached stable levels, rats were exposed to sessions with a progressive ratio schedule of reinforcement. The effect of nonsedative doses of baclofen (0, 1, and 3 mg/kg, i.p.) and GS39783 (0, 25, 50, and 100 mg/kg, i.g.) on breakpoint for alcohol and sucrose (defined as the lowest response requirement not achieved by each rat and used as index of the motivational strength of alcohol and sucrose) was determined.Results:  Baclofen administration resulted in a dose‐dependent decrease in breakpoint for alcohol; this effect was not specific, as baclofen also reduced—to a comparable extent—breakpoint for sucrose. Conversely, GS39783 administration resulted in a dose‐dependent and completely specific reduction in breakpoint for alcohol.Conclusions:  The present results (i) confirm previous data on baclofen’s capacity to suppress, although nonspecifically, alcohol’s motivational properties, and (ii) extend to alcohol’s motivational properties the capacity of GS39783 to inhibit alcohol drinking and reinforcement in rats.
Salivary Acetaldehyde Concentration According to Alcoholic Beverage Consumed and Aldehyde Dehydrogenase‐2 Genotype
Authors: Yokoyama Akira , Tsutsumi Eri , Imazeki Hiromi , Suwa Yoshihide , Nakamura Chizu , Mizukami Takeshi , Yokoyama Tetsuji 
Published: July 2008

Background:  Acetaldehyde is suspected of playing a critical role in cancer development in the upper aerodigestive tract (UADT). The high salivary acetaldehyde levels after alcohol drinking are partly due to acetaldehyde production by oral bacteria. Some alcoholic beverages, especially Calvados and shochu, contain very high levels of acetaldehyde. Inactive heterozygous aldehyde dehydrogenase‐2 (ALDH2) increases the risk of UADT cancer in drinkers.Methods:  In a randomized cross‐over design study, 19 healthy Japanese volunteers ingested 0.6 g ethanol/kg body weight in the form of 13% ethanol Calvados, 13% ethanol shochu, 13% ethanol red wine, and 5% ethanol beer under the fasting conditions at 3‐week intervals. We monitored blood and salivary acetaldehyde concentrations immediately after drinking, and 30, 60, 90, 120, and 180 minutes after completion of drinking.Results:  The acetaldehyde concentration of each beverage was: Calvados 0.60 mM (1.86 mM in 40% undiluted solution), shochu 0.60 mM (1.16 mM in 25% undiluted solution), red wine 0.25 mM, and beer 0.14 mM. The salivary acetaldehyde concentration immediately after drinking wine was significantly lower than the other beverages, and it was significantly lower immediately after drinking beer than Calvados. The acetaldehyde concentrations 30 to 180 minutes after drinking were unrelated to the beverage type. Throughout the observation period the salivary acetaldehyde concentrations were much higher than the blood acetaldehyde concentrations in all 12 active ALDH2 homozygotes (24 to 53 μM in saliva vs. 2 to 5 μM in blood) and in all 7 inactive ALDH2 heterozygotes (37 to 76 μM in saliva vs. 12 to 25 μM in blood), and they were 13 to 25 μM higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes after adjusting for age, body weight, sex, smoking and drinking habits, and time since the last toothbrushing. The values after subtracting the blood acetaldehyde concentration from the salivary acetaldehyde concentration were also higher in the ALDH2 heterozygotes than in the ALDH2 homozygotes.Conclusions:  There are differences in exposure of the UADT to high salivary acetaldehyde concentrations according to the type of alcoholic beverage and ALDH2 genotype, and the differences partly explain the differences in the cancer susceptibility of the UADT according to alcoholic beverage and ALDH2 genotype.
Ventriculo‐peritoneal shunt infection in a patient on hemodialysis
Authors: THET Yupar , MYINT Wynne , HUGHES David , CROWE Alex V. , BANERJEE Anindya 
Published: July 2008

AbstractSepsis is an important and serious complication in hemodialysis (HD) patients. Here we report on a case of spina bifida with ventriculo‐peritoneal (VP) shunt infection who was on HD and underwent at least 5 months of investigations before a source of the infection was found and eventually treated successfully. We believe this to be the first reported case of VP shunt‐associated sepsis in a patient on HD.
Toward the wearable artificial kidney
Authors: RONCO Claudio , DAVENPORT Andrew , GURA Victor 
Published: July 2008

AbstractThe evolution of technology in hemodialysis has gone through several steps including the feasibility phase, the search for reliability, the implementation of automation to improve efficiency and the quest towards increased tolerance and treatment adequacy. Today, a new challenge is appearing on the scene and it concerns miniaturization, transportability, wearability and the possibility of developing implantable devices for renal replacement therapies. Although we are not there yet, a new series of papers have recently been published disclosing interesting and promising results on the application of wearable ultrafiltration systems (WUF) and wearable artificial kidneys (WAK). Some of these use extracorporeal blood cleansing as a method of blood purification while others use peritoneal dialysis as a treatment modality. This manuscript presents the initial results with these new devices and proposes an effort to make a quantum leap in technology making the wearable artificial kidney a reality rather than a dream.
What limits the expansion of self‐care dialysis at home?
Authors: LEDEBO Ingrid 
Published: July 2008

AbstractSelf‐care dialysis at home, whether peritoneal dialysis or hemodialysis, is more cost‐effective than in‐center dialysis and treatment outcome is at least comparable. Still, both self‐care modalities are considered underutilized and we wished to identify the perceived reasons for this underutilization among nephrology professionals. A questionnaire was distributed at 5 international nephrology meetings in 2006. Questions addressed the most important stakeholders and the most important issues for patients and nephrology professionals to enable the expansion of self‐care dialysis and commonly mentioned barriers were given as alternative responses. The proportion of patients considered suitable for self‐care was also investigated. Seven thousand responses were collected. The listed stakeholders, i.e., health care and reimbursement authorities, nurses and physicians, and finally patients and their families, are considered approximately equally important for the process. Nephrology professionals feel that patient motivation for choosing and performing self‐care dialysis is the strongest driver. The need for dedicated resources for self‐care is judged to be vital for the expansion of this modality of treatment. Thirty‐two percent of incident patients are considered able to perform self‐care dialysis at home. This international survey among 7000 nephrology professionals has identified patient motivation as one of the strongest drivers of self‐care dialysis at home. The need for dedicated resources for the staff to devote time to developing such motivation is given as one of the major reasons for the slow adoption. Under ideal conditions, it is felt that one‐third of all patients starting dialysis can be trained to perform self‐care dialysis.
The immune reaction against allogeneic necrotic cells is reduced in Annexin A5 knock out mice whose macrophages display an anti‐inflammatory phenotype
Authors: Frey Benjamin , Munoz Luis E. , Pausch Friederike , Sieber Renate , Franz Sandra , Brachvogel Bent , Poschl Ernst , Schneider Holm , Rödel Franz , Sauer Rolf , Fietkau Rainer , Herrmann Martin , Gaipl Udo S. 
Published: July 2008

AbstractProteins of the annexin family bind to phospholipids in a Ca2+ dependent manner. The exposure of phosphatidylserine (PS) by apoptotic as well as necrotic cells is one major eat‐me‐signal for macrophages. Annexin A5 (Anx A5) preferentially binds to PS. The availability of Anx A5 knock out (KO) mice allowed us to investigate for the first time if endogenous Anx A5 modulates the immune response towards allogeneic cells. Furthermore, the effect of Anx A5 gene deletion on the phagocytic process as well as on the inflammatory reaction of macrophages was explored. We found that Anx A5 KO mice have a strongly reduced allogeneic cellular immune reaction against primary as well as secondary necrotic cells. In vivo phagocytosis experiments revealed that macrophages of Anx A5 KO mice displayed an increased uptake of necrotic cells. Additionally, an increased secretion of the anti‐inflammatory cytokine IL‐10 of isolated macrophages of Anx A5 KO mice after contact with necrotic cells was observed. Furthermore, the promoter activity of the Anx A5 gene was enhanced after stimulation of macrophages. The tumour size of an allogeneic tumour regressed faster when endogenous Anx A5 was present. These data demonstrate that endogenous Anx A5 influences the phagocytosis of necrotic cells, modulates the immune response towards allogeneic cells and acts as an inflammatory protein.
GFP‐tagged proteins visualized by freeze‐fracture immuno‐electron microscopy: a new tool in cellular and molecular medicine
Authors: Robenek Horst , Buers Insa , Hofnagel Oliver , Lorkowski Stefan , Severs Nicholas J. 
Published: July 2008

AbstractGFP‐tagging is widely used as a molecular tool to localize and visualize the trafficking of proteins in cells but interpretation is frequently limited by the low resolution afforded by fluorescence light microscopy. Although complementary thin‐section immunogold electron microscopic techniques go some way in aiding interpretation, major limitations, such as relatively poor structural preservation of membrane systems, low labelling efficiency and the two‐dimensional nature of the images, remain. Here we demonstrate that the electron microscopic technique freeze‐fracture replica immunogold labelling overcomes these disadvantages and can be used to define, at high resolution, the precise location of GFP‐tagged proteins in specific membrane systems and organelles of the cell. Moreover, this technique provides information on the location of the protein within the phospholipid bilayer, potentially providing insight into mis‐orientation of tagged proteins compared to their untagged counterparts. Complementary application of the freeze‐fracture replica immunogold labelling technique alongside conventional fluorescence microscopy is seen as a novel and valuable approach to verification, clarification and extension of the data obtained using fluorescent‐tagged proteins. The application of this approach is illustrated by new findings on PAT‐family proteins tagged with GFP transfected into fibroblasts from patients with Niemann‐Pick type C disease.
Cysteinylation and homocysteinylation of plasma protein thiols during ageing of healthy human beings
Authors: Rossi R. , Giustarini D. , Milzani A. , Dalle‐Donne I. 
Published: July 2008

AbstractThe purpose of the present study was to determine the relative amount of S‐thiolated proteins (i.e. S‐homocysteinylated, S‐cysteinylglycinylated, S‐glutathionylated and S‐cysteinylated proteins) to the total protein thiols (i.e. the sum of reduced protein sulphydryl groups (PSHs) and protein mixed disulphides with homocysteine [HcySH], cysteinylglycine, cysteine [CysSH] and glutathione) in the plasma of healthy individuals aged 20 to 93. After plasma separation, total protein thiols, S‐thiolated proteins, as well as CysSH, cystine, HcySH and homocystine were measured by high‐performance liquid chromatography (HPLC) with fluorescence determination of the thiol‐monobromobimane conjugate. Determination of plasma levels of protein thiols was performed by spectrophotometry with 5,5′‐dithiobis(2‐nitrobenzoic acid) as a titrating agent. The present study demonstrates an age‐dependent reduction in the amount of PSHs, and an age‐dependent increase in cysteinylated and homocysteinylated plasma proteins in healthy human beings. This indicates that the efficiency of the reduced protein thiol pool as an antioxidant defence system decreases with age, possibly causing an increased risk of irreversible oxidation (i.e. further oxidation to sulphinic and sulphonic acids, which are usually not reducible by thiol reducing agents) of sulphydryl groups of plasma proteins. The drop in the plasma level of protein sulphydryl groups suggests depletion and/or impairment of the antioxidant capacity of plasma, likely related to an alteration of the delicate balance between the different redox forms of thiols.
microRNAs and prostate cancer
Authors: Shi Xu‐Bao , Tepper Clifford G. , White Ralph W. deVere 
Published: July 2008

Introduction
miRNAs and human cancer
Aberrant expression of miRNAs in prostate cancer
Biological function of prostate cancer‐related miRNAs
Identification of targets of prostate cancer‐related miRNAs
Regulation of miRNAs in prostate cancer
Potential application of miRNAs in prostate cancer
Conclusions

AbstractProstate cancer (CaP) is the most frequently diagnosed malignant tumour and the second leading cause of cancer deaths in American men. One of the most troubling aspects of this disease is that, after androgen ablation therapy, androgen‐dependent cancer cells inevitably progress to an androgen‐independent status, for which no effective treatment has yet been developed. To date, the mechanisms that underlie the occurrence and progression of CaP remain largely unknown. Recent studies suggest that microRNAs (miRNAs) are involved in human tumourigenesis. Some aberrantly expressed miRNAs have been discovered in CaP cell lines, xenografts and clinical tissues and these CaP‐related miRNAs may play critical roles in the pathogenesis of CaP. This review provides an overview of current findings about aberrantly expressed miRNAs in CaP. Although a number of CaP‐related miRNAs were discovered, to date, only five are characterized for their functionalities: three as oncogenes and two as tumour suppressors. To understand the mechanisms of miRNA action as oncogenes or tumour suppressors, mRNA targets of miRNAs were characterized. Oncogenic miRNAs down‐regulate the expression of apoptosis‐related genes, and tumour suppressor miRNAs target the proliferation‐related genes. Importantly, there is evidence that CaP‐related miRNAs are regulated through androgen signalling and that this regulation may contribute to the development of androgen independence. Due to the oncogenic or tumour‐suppressive properties of CaP‐related miRNAs, they are highly likely to be of clinical use first as biomarkers but more importantly as therapeutic targets for prostate cancer treatment in the near future.
E2F1 represses β‐catenin/TCF activity by direct up‐regulation of Siah1
Authors: Xie Wei , Jin Lei , Mei Yide , Wu Mian 
Published: July 2008

AbstractTranscription factor E2F1 is a key regulator of cell proliferation and apoptosis. Its activity is strictly controlled by the pRB/E2F pathway. In the majority of cancer cells, however, this pathway is frequently found deregulated, and the underlying mechanism involving transcriptional control by E2F1 has not yet been fully elucidated. Here we report the identification of two putative E2F1‐binding sites located upstream from Siah1 transcription start site (+1). Chromatin immunoprecipitation assay reveals that transcription factor E2F1 is capable of binding to the putative sites, and luciferase reporter assay shows that E2F1 can activate transcription from the Siah1 promoter. Ectopic expression of E2F1 elevates the Siah1 level, hence suppressing the β‐catenin/TCF activity. Consistently, knock‐down of endogenous E2F1 by a shRNA strategy results in reduced expression of Siah1. Moreover, repression of β‐catenin/TCF activity by E2F1 can be attenuated by shRNA‐based repression of endogenous Siah1, implying that Siah1 is a bona fide E2F1 target gene, which at least partly, mediates the suppression of β‐catenin/TCF signalling pathway.
The natural compound atraric acid is an antagonist of the human androgen receptor inhibiting cellular invasiveness and prostate cancer cell growth
Authors: Papaioannou Maria , Schleich Sonja , Prade Ina , Degen Stephanie , Roell Daniela , Schubert Undine , Tanner Tamzin , Claessens Frank , Matusch Rudolf , Baniahmad Aria 
Published: July 2008

AbstractExtracts from Pygeum africanum are used in the treatment of prostatitis, benign prostatic hyperplasia and prostate cancer (Pca), major health problems of men in Western countries. The ligand‐activated human androgen receptor (AR) supports the growth of the prostate gland. Inhibition of human AR by androgen ablation therapy and by applying synthetic anti‐androgens is therefore the primary goal in treatment of patients. Here, we show that atraric acid (AA) isolated from bark material of Pygeum africanum has anti‐androgenic activity, inhibiting the transactivation mediated by the ligand‐activated human AR. This androgen antagonistic activity is receptor specific and does not inhibit the closely related glucocorticoid or progesterone receptors. Mechanistically, AA inhibits nuclear transport of AR. Importantly, AA is able to efficiently repress the growth of both the androgen‐dependent LNCaP and also the androgen‐independent C4–2 Pca cells but not that of PC3 or CV1 cells lacking AR. In line with this, AA inhibits the expression of the endogenous prostate specific antigen gene in both LNCaP und C4–2 cells. Analyses of cell invasion revealed that AA inhibits the invasiveness of LNCaP cells through extracellular matrix. Thus, this study provides a molecular insight for AA as a natural anti‐androgenic compound and may serve as a basis for AA derivatives as a new chemical lead structure for novel therapeutic compounds as AR antagonists, that can be used for prophylaxis or treatment of prostatic diseases.
Osteopontin as two‐sided mediator of intestinal inflammation
Authors: Heilmann Katja , Hoffmann Ute , Witte Ellen , Loddenkemper Christoph , Sina Christian , Schreiber Stefan , Hayford Claudia , Holzlbhner Pamela , Wolk Kerstin , Tchatchou Elianne , Moos Verena , Zeitz Martin , Sabat Robert , Giinthert Ursula , Wittig Bianca Maria 
Published: July 2008

AbstractOsteopontin (OPN) is characterized as a major amplifier of Th1‐immune responses. However, its role in intestinal inflammation is currently unknown. We found considerably raised OPN levels in blood of wild‐type (WT) mice with dextran sodium sulfate (DSS)‐induced colitis. To identify the role of this mediator in intestinal inflammation, we analysed experimental colitis in OPN‐deficient (OPN−/−) mice. In the acute phase of colitis these mice showed more extensive colonic ulcerations and mucosal destruction than WT mice, which was abrogated by application of soluble OPN. Within the OPN−/– mice, infiltrating macrophages were not activated and showed impaired phagocytosis. Reduced mRNA expression of interleukin (IL)‐1 β and matrix metalloproteinases was found in acute colitis of OPN−/– mice. This was associated with decreased blood levels of IL‐22, a Th17 cytokine that may mediate epithelial regeneration. However, OPN–/– mice showed increased serum levels of tumour necrosis factor (TNF)‐α, which could be due to systemically present lipopolysaccharide translocated to the gut. In contrast to acute colitis, during chronic DSS‐colitis, which is driven by a Th1 response of the lamina propria infiltrates, OPN−/– mice were protected from mucosal inflammation and demonstrated lower serum levels of IL‐12 than WT mice. Furthermore, neutralization of OPN in WT mice abrogated colitis. Lastly, we demonstrate that in patients with active Crohn's disease OPN serum concentration correlated significantly with disease activity. Taken together, we postulate a dual function of OPN in intestinal inflammation: During acute inflammation OPN seems to activate innate immunity, reduces tissue damage and initiates mucosal repair whereas during chronic inflammation it promotes the Th1 response and strengthens inflammation.
Follicular streamers (stelae) in scarring and non‐scarring alopecia
Authors: Horenstein Marcelo G. , Jacob Jack S. 
Published: July 2008

Background:  Follicular streamers are residual fibrovascular tracts representing the impermanent lower third of the hair follicle below the bulge region. Streamers are generally not counted in transverse alopecia samples as they may represent catagen/telogen (CT) follicles and vellus‐like (VL) follicles, or be mistaken as follicular scars.Design:  We evaluated 22 non‐scarring alopecia cases, including alopecia areata (AA) and androgenetic alopecia (AGA), and 22 scarring alopecia cases, including follicular degeneration syndrome (FDS)/central centrifugal cicatricial alopecia and other scarring alopecia (OSA) disorders. We counted terminal follicular streamers found at a deep dermal level (L2) and followed them into a mid‐dermal level at the central follicular unit (FU) to determine their precise derivation.Results:  We found streamers in 8/9 AA, 11/13 AGA, 6/12 FDS and 3/10 OSA cases. We counted a total of 74 streamers at L2, including 61 in non‐scarring alopecia cases (p < 0.001). At the more superficial FU level, 72% of streamers corresponded to CT follicles, 25% to VL follicles and 3% to follicular scars.Conclusions:  Follicular streamers are found predominantly in non‐scarring alopecia cases. Streamers found at deep dermal or subcutaneous levels should be followed and identified at the FU level in order to obtain accurate follicular counts and follicular ratios needed for non‐scarring alopecia diagnosis.