bluuebunny/crossref_metadata_2025 huggingface dataset:
Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis
Authors: Koopman René , Beelen Milou , Stellingwerff Trent , Pennings Bart , Saris Wim H. M. , Kies Arie K. , Kuipers Harm , van Loon Luc J. C.
Published: July 2007

The present study was designed to assess the impact of coingestion of various amounts of carbohydrate combined with an ample amount of protein intake on postexercise muscle protein synthesis rates. Ten healthy, fit men (20 ± 0.3 yr) were randomly assigned to three crossover experiments. After 60 min of resistance exercise, subjects consumed 0.3 g·kg−1·h−1 protein hydrolysate with 0, 0.15, or 0.6 g·kg−1·h−1 carbohydrate during a 6-h recovery period (PRO, PRO + LCHO, and PRO + HCHO, respectively). Primed, continuous infusions with l-[ ring-13C6]phenylalanine, l-[ ring-2H2]tyrosine, and [6,6-2H2]glucose were applied, and blood and muscle samples were collected to assess whole body protein turnover and glucose kinetics as well as protein fractional synthesis rate (FSR) in the vastus lateralis muscle over 6 h of postexercise recovery. Plasma insulin responses were significantly greater in PRO + HCHO compared with PRO + LCHO and PRO (18.4 ± 2.9 vs. 3.7 ± 0.5 and 1.5 ± 0.2 U·6 h−1·l−1, respectively, P < 0.001). Plasma glucose rate of appearance (Ra) and disappearance (Rd) increased over time in PRO + HCHO and PRO + LCHO, but not in PRO. Plasma glucose Ra and Rd were substantially greater in PRO + HCHO vs. both PRO and PRO + LCHO ( P < 0.01). Whole body protein breakdown, synthesis, and oxidation rates, as well as whole body protein balance, did not differ between experiments. Mixed muscle protein FSR did not differ between treatments and averaged 0.10 ± 0.01, 0.10 ± 0.01, and 0.11 ± 0.01%/h in the PRO, PRO + LCHO, and PRO + HCHO experiments, respectively. In conclusion, coingestion of carbohydrate during recovery does not further stimulate postexercise muscle protein synthesis when ample protein is ingested.
Smoking impairs muscle protein synthesis and increases the expression of myostatin and MAFbx in muscle
Authors: Petersen Anne Marie Winther , Magkos Faidon , Atherton Philip , Selby Anna , Smith Kenneth , Rennie Michael J. , Pedersen Bente Klarlund , Mittendorfer Bettina
Published: July 2007

Smoking causes multiple organ dysfunction. The effect of smoking on skeletal muscle protein metabolism is unknown. We hypothesized that the rate of skeletal muscle protein synthesis is depressed in smokers compared with non-smokers. We studied eight smokers (≥20 cigarettes/day for ≥20 years) and eight non-smokers matched for sex (4 men and 4 women per group), age (65 ± 3 and 63 ± 3 yr, respectively; means ± SEM) and body mass index (25.9 ± 0.9 and 25.1 ± 1.2 kg/m2, respectively). Each subject underwent an intravenous infusion of stable isotope-labeled leucine in conjunction with blood and muscle tissue sampling to measure the mixed muscle protein fractional synthesis rate (FSR) and whole body leucine rate of appearance (Ra) in plasma (an index of whole body proteolysis), the expression of genes involved in the regulation of muscle mass (myostatin, a muscle growth inhibitor, and MAFBx and MuRF-1, which encode E3 ubiquitin ligases in the proteasome proteolytic pathway) and that for the inflammatory cytokine TNF-α in muscle, and the concentration of inflammatory markers in plasma (C-reactive protein, TNF-α, interleukin-6) which are associated with muscle wasting in other conditions. There were no differences between nonsmokers and smokers in plasma leucine concentration, leucine rate of appearance, and plasma concentrations of inflammatory markers, or TNF-α mRNA in muscle, but muscle protein FSR was much less (0.037 ± 0.005 vs. 0.059 ± 0.005%/h, respectively, P = 0.004), and myostatin and MAFBx (but not MuRF-1) expression were much greater (by ∼33 and 45%, respectivley, P < 0.05) in the muscle of smokers than of nonsmokers. We conclude that smoking impairs the muscle protein synthesis process and increases the expression of genes associated with impaired muscle maintenance; smoking therefore likely increases the risk of sarcopenia.
Signaling pathways initiated by β-hydroxy-β-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli
Authors: Eley Helen L. , Russell Steven T. , Baxter Jeffrey H. , Mukerji Pradip , Tisdale Michael J.
Published: July 2007

To investigate the mechanism by which β-hydroxy-β-methylbutyrate (HMB) attenuates the depression of protein synthesis in the skeletal muscle of cachectic mice, a study has been carried out in murine myotubes in the presence of proteolysis-inducing factor (PIF). PIF inhibited protein synthesis by 50% within 4 h, and this was effectively attenuated by HMB (25–50 μM). HMB (50 μM) alone stimulated protein synthesis, and this was attenuated by rapamycin (27 nM), an inhibitor of mammalian target of rapamycin (mTOR). Further evidence for an involvement of this pathway was shown by an increased phosphorylation of mTOR, the 70-kDa ribosomal S6 kinase (p70S6k), and initiation factor 4E-binding protein (4E-BP1) and an increased association of eukaryotic initiation factor 2 (eIF4E) with eIF4G. PIF alone induced a transient (1–2 h) stimulation of phosphorylation of mTOR and p70S6k. However, in the presence of HMB, phosphorylation of mTOR, p70S6k, and 4E-BP1 was increased, and inactive 4E-BP1-eIF4E complex was reduced, whereas the active eIF4G·eIF4E complex was increased, suggesting continual stimulation of protein synthesis. HMB alone reduced phosphorylation of elongation factor 2, but this effect was not seen in the presence of PIF. PIF induced autophosphorylation of the double-strand RNA-dependent protein kinase (PKR), leading to phosphorylation of eIF2 on the α-subunit, which would inhibit protein synthesis. However, in the presence of HMB, phosphorylation of PKR and eIF2α was attenuated, and this was also observed in skeletal muscle of cachectic mice administered HMB (0.25 g/kg). These results suggest that HMB attenuates the depression of protein synthesis by PIF in myotubes through multiple mechanisms.
Proapoptotic activity of indoleamine 2,3-dioxygenase expressed in renal tubular epithelial cells
Authors: Mohib Kanishka , Guan Qiunong , Diao Hong , Du Caigan , Jevnikar Anthony M.
Published: July 2007

Exposure of renal tubular epithelial cells (TEC) to IFN-γ/TNF-α leads to Fas/FasL-mediated self-injury, which contributes to allograft rejection. Indoleamine 2,3-dioxygenase (IDO) converts tryptophan to N-formyl-kynurenine and contributes to immune privilege in tissues by increasing Fas-mediated T cell apoptosis. However, renal expression of IDO and its role in promoting Fas-mediated TEC death have not been examined. IDO expression was analyzed by RT-PCR and Western blot. Apoptosis was measured by fluorescence-activated cell sorting analysis and terminal deoxytransferase-mediated dUTP nick end labeling. We demonstrated that functional IDO is expressed in TEC and is increased by IFN-γ/TNF-α exposure. Increased IDO activity promoted TEC apoptosis, whereas inhibition of IDO by its specific inhibitor 1-methyl-d-tryptophan attenuated IFN-γ/TNF-α-mediated TEC apoptosis and augmented TEC survival. Transgenic expression of IDO resulted in increased TEC apoptosis in the absence of proinflammatory cytokine exposure, supporting a central role for IDO in TEC injury. Inhibition of IDO-mediated TEC death by a caspase-8-specific inhibitor (Z-IETD-FMK), as well as the absence of an IDO effect in Fas-deficient and FasL-deficient TEC, supports a Fas/FasL-dependent, caspase-8-mediated mechanism for IDO-enhanced TEC death. These data suggest that renal IDO expression may be deleterious during renal inflammation, because it enhances TEC self-injury through Fas/FasL interactions. Thus attenuation of IDO may represent a novel strategy to promote kidney function following ischemia and renal allograft rejection.
Discordant effects of corticosteroids and expression of subunits on ENaC activity
Authors: Husted Russell F. , Volk Kenneth A. , Sigmund Rita D. , Stokes John B.
Published: July 2007

In renal distal nephron and airway epithelial cells, adrenocortical steroids increase epithelial Na+channel (ENaC) activity and also markedly increase the expression of the α-subunit. The present experiments were designed to reconstitute this steroid effect in ENaC-expressing cells by overexpressing the subunits whose expression is enhanced by corticosteroids. In renal collecting duct monolayers, corticosteroids increased ENaC activity 5- to 8-fold, endogenous α-ENaC mRNA and protein ∼10-fold, and β-ENaC protein and mRNA 1.2- to 2-fold. γ-ENaC expression was unchanged. To determine whether this increase in expression was sufficient to increase ENaC activity, we used a regulated adenovirus system to increase expression of each subunit alone and in combination. Unexpectedly, increased expression of the α- and/or β-subunit had no effect on ENaC activity in collecting duct cells or lung epithelial cells. In contrast, a small increase in γ-ENaC expression increased ENaC activity about threefold. This increase in activity was additive to the effect of steroids. Thus, even though corticosteroids strongly increase α-ENaC expression and moderately increase β-ENaC expression, these effects are not, by themselves, sufficient to increase ENaC activity. Knockdown experiments are consistent with the idea that the increased expression of α-ENaC is necessary for the full steroid effect on ENaC. Increased expression of γ-ENaC and corticosteroid treatment enhances ENaC activity by parallel, noninteracting pathways. These results underscore the importance of other actions of steroid hormones for long-term enhancement of ENaC activity and raise new possibilities for regulation of ENaC activity by γ-ENaC expression.
Melanophilin, a novel aldosterone-induced gene in mouse cortical collecting duct cells
Authors: Martel Jessica A. , Michael Donna , Fejes-Tóth Géza , Náray-Fejes-Tóth Anikó
Published: July 2007

The molecular mechanisms of aldosterone-regulated Na+transport are not entirely clear. The goal of this study was to identify aldosterone-induced genes potentially involved in the trafficking of the epithelial Na+channel (ENaC). We report that the transcript levels of melanophilin (MLPH), a protein involved in vesicular trafficking in melanocytes, are rapidly increased by aldosterone in cortical collecting duct (CCD) cells. This effect was near maximal at physiological aldosterone concentrations, indicating that it is mediated by the mineralocorticoid receptor. De novo protein synthesis is not required for the induction of MLPH mRNA by aldosterone. To determine whether this induction has functional consequences on transepithelial Na+current, we generated clonal CCD cell lines that express a tetracycline-inducible MLPH. Induction of MLPH in these cells led to a relatively modest, but statistically significant, increase in amiloride-sensitive Na+current, suggesting the MLPH may be involved in ENaC trafficking. MyosinVc, the epithelial-specific class V myosin that is highly homologous to MyosinVa, another component of the melanosome trafficking complex, has putative consensus sites for serum and glucocorticoid-induced kinase 1 (SGK1), an early aldosterone-induced kinase that mediates some of aldosterone's effects on Na+transport. Our results indicate that MyosinVc is phosphorylated by endogenous SGK1, suggesting that this complex may be involved in the aldosterone-regulated trafficking of ENaC in the CCD. These results suggest potential mechanisms by which aldosterone may regulate Na+transport both directly, by increasing the abundance of MLPH, and indirectly by increasing the transcription of SGK1, which in turn regulates the activity of MyosinVc.
Diagnosis of Constipation in Children
Authors: Sauvat Frédérique
Published: July 2007

Constipation is a frequent reason for consulting a pediatrician. As a symptom, constipation can be due to various etiologies in terms of frequency, nature and seriousness. Constipation may be of medical or surgical origin or idiopathic. Surgical etiologies are mainly represented by Hirschsprung’s disease. It is the main differential diagnosis even if it is 50 times less frequent than idiopathic or functional constipation. A thorough history and physical examination, including anal examination, are the best way to reach a diagnosis. No other examination is required in most of the cases and all investigations have to be managed according to clinical considerations.
Adult Neurogenesis and Local Neuronal Progenitors in the Striatum
Authors: Luzzati Federico , De Marchis Silvia , Fasolo Aldo , Peretto Paolo
Published: July 2007

Mechanisms underlying neurogenesis in the subventricular-zone-olfactory-bulb system and dentate gyrus of the hippocampus are beginning to be delineated and show common regulative features. In both regions neurogenesis is attributable to progenitor cells whose progeny progressively matures to functional neurons under genetic and epigenetic influence. Persistence of endogenous neuronal progenitors and integration of new neurons in preexisting circuits provide an appealing model of study to develop therapy strategies for neurodegenerative diseases. Interestingly, comparative analysis in mammals indicates that low neurogenic activity is also present in regions classically considered nonneurogenic in both normal and pathological conditions. Neurogenesis in these regions can be due to progenitors derived from the subventricular germinal zone and/or local parenchymal progenitors. Although, in vivo, the origin, identity and putative function of parenchymal progenitors are still obscure, in vitro studies suggest that many regions of the adult central nervous system potentially contain multipotent parenchymal progenitors. The aim of this review is to delineate the common regulative features underlying adult neurogenesis in the main neurogenic regions and in the striatum focusing on our recent data concerning the existence of local parenchymal progenitors in the caudate nucleus of the adult rabbit.
Histamine Induces MUC5AC Expression via a hCLCA1 Pathway
Authors: Kim Yong Min , Won Tae-Bin , Kim Si Whan , Min Yang-Gi , Lee Chul Hee , Rhee Chae-Seo
Published: July 2007

Background: Histamine is an important inflammatory mediator and associated with early phase allergic response. However, the involvement of histamine in mucin gene expression or production has not been elucidated. Objective: The aim of this study is to investigate whether histamine induces MUC5AC production in NCI-H292 cells, and to evaluate which pathway is involved in this mucin production. Methods: MUC5AC production in NCI-H292 cells was analyzed by RT-PCR, immunoassay and immunocytochemical analysis. The effect of histamine on MUC5AC production in these cells at different time courses and concentrations was assessed, and the relationship between hCLCA1 expression and histamine concentration was also evaluated. In addition, cells were pretreated with antihistamine or an hCLCA1 blocker (niflumic acid, NFA) to evaluate the mechanism underlying histamine-induced MUC5AC production. Results: Histamine upregulated MUC5AC gene expression and mucin protein production in a dose-dependent and time-related fashion. Histamine also dose-dependently increased hCLCA1 mRNA expression. Moreover, pretreatment of cells with chlorpheniramine or NFA reduced histamine-induced MUC5AC mRNA expression and protein production in these cells. The histamine-treated cells showed increased cytoplasmic staining for MUC5AC compared to cells treated with media alone, and cells pretreated with chlorpheniramine or NFA before histamine treatment. Conclusion: Our results suggest that histamine-induced MUC5AC production occurs via the upregulation of hCLCA1. It is assumed that antihistamines or hCLCA1 channel blockers can partially suppress histamine-induced MUC5AC production in allergic diseases, e.g. allergic rhinitis.
Autoantibodies against Glutamate Receptor ε2-Subunit Detected in a Subgroup of Patients with Reversible Autoimmune Limbic Encephalitis
Authors: Kimura A. , Sakurai T. , Suzuki Y. , Hayashi Y. , Hozumi I. , Watanabe O. , Arimura K. , Takahashi Y. , Inuzuka T.
Published: July 2007

We investigated the presence of autoantibodies againstglutamate receptor (GluR) Ε2 in serum and cerebrospinal fluid (CSF) samples from 12 consecutive patients with acute encephalitis/encephalopathy by immunoblotting using recombinant GluRΕ2 as antigen. In 4 patients, IgM autoantibodies against GluRΕ2 were detected in CSF in the early phase of the disease but were not detectable after several months. Seizures and psychiatric symptoms were noted during the acute phase of the disease in these 4 patients, who showed various degrees of residual amnesia. Immunotherapy was performed on 3 patients (patients 1, 3 and 4), and they showed marked improvements. Immunohistochemistry using these patients’ sera showed that immunoreactivity is specifically detected in the cytoplasm of rat hippocampal and cortical neurons. The clinical features and neuroimaging findings of patients with IgM autoantibodies against GluRΕ2 in CSF resemble those of patients with reversible autoimmune limbic encephalitis.
Patients’ and Bystanders’ Awareness of Stroke and Pre-Hospital Delay after Stroke Onset: Perspectives for Thrombolysis in West Pomerania Province, Poland
Authors: Nowacki Przemysław , Nowik Marta , Bajer-Czajkowska Anna , Porębska Agata , Żywica Adrian , Nocoń Danuta , Drechsler Hanna , Safranow Krzysztof
Published: July 2007

Objective: Thrombolysis is a time-dependent therapy. It is therefore very important how fast stroke patients can reach hospital. The present study was designed to assess which proportion of patients with stroke (from the population of Szczecin, the capital of West Pomerania Province, Poland) reaches hospital within the recommended time from the thrombolytic therapy point of view. The purpose of our study was also to elucidate which factors can influence the time before the ambulance service is called. Patients and Methods: The study involved 1,015 patients with stroke admitted to the Emergency Department of the University Hospital, Szczecin. Results: 235 patients (23.1%) were admitted to the hospital within the appropriate period for thrombolytic therapy. Hospital arrival time was significantly earlier in older patients and in patients with severer neurological deficits. We also observed a tendency for faster hospitalization of women, the highly educated, and patients regularly using antiplatelet drugs for cardiovascular disease prevention. Conclusions: The percentage of stroke patients hospitalized within 2 h after stroke onset should be increased. The most susceptible subpopulations in our country seem to be older patients, the highly educated and patients regularly using antiplatelet drugs for cardiovascular disease prevention.
Restless Legs Syndrome in Hemodialysis Patients: Association with Calcium Antagonists
Authors: Telarović Srđana , Relja Maja , Trkulja Vladimir
Published: July 2007

Uremia-related restless legs syndrome (RLS) is a known form of secondary RLS. This cross-sectional survey included patients (n = 82) on stable hemodialysis (HD; >3 months, Kt/V >1.2) who were iron-replete, free of neurodegenerative or psychiatric disorders, severe polyneuropathy and radiculopathy, not exposed to antipsychotics/antidepressants, and not severely anemic. Forty-nine (60%) were RLS ‘positive’, and 25 (31%) had severe/very severe symptoms (International Restless Legs Syndrome Study Group criteria). None had been diagnosed previously. In a multivariate analysis, the prevalence of RLS was higher in diabetic patients [vs. nondiabetics; prevalence ratio (PR) 2.32, 95% CI 1.50–3.60, p < 0.001] and those exposed to Ca2+ antagonists (vs. nonexposed; PR 2.02, CI 1.47–2.76, p < 0.001), and also increased with dialysis duration (PR 1.05, 95% CI 1.02–1.09, p < 0.001). Association of Ca2+ antagonists and RLS in uremic patients has not been reported previously and deserves further research.
Classification of Phenotype Characteristics in Adult-Onset Spinal Muscular Atrophy
Authors: Gdynia Hans-Jürgen , Sperfeld Anne-Dorte , Flaith Leonie , Kuehnlein Peter , Unrath Alexander , Ludolph Albert C. , Kassubek Jan
Published: July 2007

Background/Aims: Degenerative lower motor neuron diseases (LMND) encompass a group of rare clinically and genetically heterogeneous disorders with the hallmark of anterior horn cell degeneration in the spinal cord and brainstem. In a recently proposed classification, LMND were subdivided according to the clinical disease pattern and time course. This study was performed to investigate the clinical practicability of the classification. Methods: In 22 patients with adult LMND (mean disease duration, 24 years), the disease course and detailed clinical, electrophysiological, magnetic resonance imaging, laboratory, and genetic investigations were analyzed. Results: All patients could be assigned to the distinct disease subgroups, i.e. 11 patients to the slowly progressive generalized form (group 1), one to the distal form (group 2), 3 to the segmental distal form (group 3a), and seven to the segmental proximal form (group 3b). Conclusions: The proposed classification was confirmed to be a practicable tool, and additional implications for the classification of LMND could be drawn from the data in our patient sample.
PPAR-γ Activation Inhibits Angiotensin II Synthesis, Apoptosis, and Proliferation of Mesangial Cells from Spontaneously Hypertensive Rats
Authors: Efrati Shai , Berman Sylvia , Ilgiyeav Eduard , Averbukh Zhan , Weissgarten Joshua
Published: July 2007

Background/Aim: The angiotensin II level is elevated in subjects genetically prone to develop hypertension, triggering renal hypercellularity, cytokine production, and matrix deposition. Angiotensin-converting enzyme inhibition and/or angiotensin II type 1 receptor blockade attenuate renal damage. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist possessing antihypertensive and anti-inflammatory properties, was demonstrated to provide better renal protection than angiotensin-converting enzyme inhibitors. We studied the effects of in vivo peroxisome proliferator-activated receptor gamma activation by rosiglitazone on angiotensin II synthesis, proliferation, and apoptosis of mesangial cells of spontaneously hypertensive rats versus normotensive Sprague-Dawley rats. Methods: The animals consumed either a high-sodium diet (8% Na) or a normal-sodium diet (0.5% Na). Half of each group received rosiglitazone at 5 mg/kg/day. After 3 weeks, all rats were sacrificed and the mesangial cells isolated and cultured. Angiotensin II was assessed by radioimmunoassay, apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay, and cell proliferation by [3H]thymidine incorporation. Results: Only the spontaneously hypertensive rats which consumed the high-sodium diet developed hypertension (185 ± 6 mm Hg vs. basal 128 ± 5 mm Hg; p = 0.0007) which was attenuated by rosiglitazone (to 126 ± 4 mm Hg; p = 0.34). Angiotensin II synthesis, proliferation, and apoptosis were exaggerated in mesangial cell cultures from Sprague-Dawley rats and, more so, spontaneously hypertensive rats fed the high-sodium diet, but were inhibited in cultures from rosiglitazone-treated animals. Conclusions: Peroxisome proliferator-activated receptor gamma activation, in addition to lowering blood pressure, suppresses angiotensin II synthesis and downregulates angiotensin-II-mediated proliferation and apoptosis of mesangial cells. In the context of hypertension-induced renal damage, this would mean that the renoprotective role of rosiglitazone extends beyond glycemic and lipidemic control.
Study on the Relationship between Lymphatic Vessel Density and Distal Intramural Spread of Rectal Cancer
Authors: Chen W. , Shen W. , Chen M. , Cai G. , Liu X.
Published: July 2007

Background: The smallest safe margin of distal clearance for lower rectal cancer is very important for the operation. In a previous study, a few factors were found to play a role in distal intramural spread (DIS), but there are few data regarding the influence of lymphangiogenesis. We studied the relationship between lymphatic vessel density (LVD) and DIS of rectal cancer, analyzing the probable value of LVD in determining the length of distal resection of lower rectal cancer. Methods: Nine-two patients who had undergone curative resection of lower rectal cancer were included. The length of DIS, LVD and other clinicopathological factors were evaluated. Immunohistochemical lymphatic vessel staining with LYVE-1 (lymphatic vessel endothelial hyaluronan receptor) were performed to detect the LVD. Results: 44 cases had DIS (range 0.1–2.44, mean 0.31 cm), and cancer emboli were the most common modalities of DIS. The LVD of a peritumoral lesion was significantly higher than that of an intratumoral lesion; the LVD of the DIS subgroup was significantly higher than that of the no DIS subgroup, and the LVD of the 2 subgroups was significantly higher than that of normal rectal tissue. A significant correlation was shown by a rank correlation test between the length of DIS and the LVD at the periphery of the rectal cancer (n = 44, r = 0.755, p < 0.01). The LVD was also related to the extent of infiltration, lymphatic invasion and lymph node metastases. Conclusions: Lymphangiogenesis plays an important role in rectal cancer cell metastasis and patients with a higher LVD have a better prognosis. The LVD is closely correlated with DIS. These findings may be helpful in determining the distal clearance length of rectal cancer.
Induction of Anti-Carbonic-Anhydrase-II Antibody Causes Renal Tubular Acidosis in a Mouse Model of Sjögren’s Syndrome
Authors: Takemoto Fumi , Katori Hideyuki , Sawa Naoki , Hoshino Junichi , Suwabe Tatsuya , Sogawa Yoko , Nomura Kazufumi , Nakanishi Shohei , Higa Yasushi , Kanbayashi Hiroshi , Kosuga Masahiro , Sasaki Michiko , Tomioka Satoru , Yamashita Masahiro , Ubara Yoshifumi , Yamada Akira , Takaichi Kenmei , Uchida Shunya
Published: July 2007

Background/Aim: We recently reported that renal tubular acidosis (RTA) in Sjögren’s syndrome (SjS) is associated with high titers of an autoantibody against carbonic anhydrase (CA) II, an important enzyme in renal acid-base regulation. The purpose of this study was to determine whether a CA-II antibody could cause RTA in a mouse model of SjS. Methods: PL/J mice were immunized with human CA II to induce CA II antibody formation, whereas controls were injected with phosphate-buffered saline and adjuvant. After 6 weeks, anti-CA-II antibody titers were measured, then ammonium chloride was administered orally for 1 week to detect any acidification defect. Results: CA-II-immunized mice showed higher anti-CA-II antibody titers than control mice. Pathologically, lymphocytic and plasma cell infiltration was seen in the salivary glands and kidneys of CA-II-immunized mice, but not in controls. On acid loading, blood pH and urine pH decreased in both groups of mice, but the slope of urine pH versus blood pH was less steep in the CA-II-immunized mice, suggesting that these mice had an impaired ability to reduce their urine pH in the face of metabolic acidosis. Conclusion: CA-II-immunized mice had a urinary acidification defect, which may be similar to that seen in patients with SjS.
What Maintains Energy Supply at Peak Aerobic Exercise in Trained and Untrained Older Men?
Authors: Sagiv Moran , Goldhammer Ehud , Ben-Sira David , Amir Ruthie
Published: July 2007

Background: Aging-related changes occur mainly in the cardiopulmonary system and skeletal muscles, bringing about a reduction in physical performance. Consequently, maximal oxygen uptake (VO2max) decreases. Objectives: The current study investigated exercise oxygen utilization during maximal aerobic exercise in trained and untrained elderly. Methods: Fifteen trained (59.3 ± 1.1 years) and 15 untrained (60.1 ± 1.1 years) elderly underwent a peak cardiopulmonary exercise test on a bicycle ergometer. Arterial O2 was defined from echocardiograph and venous oxygen content. Results: At rest, trained compared to untrained elderly had significantly (p < 0.05) higher values of end diastolic volume (108.1 ± 5.8 and 100.7 ± 6.2 ml, respectively) and stroke volume (68.1 ± 4.3 and 57.3 ± 6.5 ml, respectively), while heart rate (68.7 ± 9.3 and 81.3 ± 8.2 beats · min–1, respectively), and mean arterial blood pressure (90.6 ± 6.9 and 95.4 ± 7.2 mm Hg, respectively) were significantly lower. At peak aerobic test, the trained elderly, compared to the untrained subjects, achieved significantly (p < 0.05) higher values of end diastolic volume (156.1 ± 8.2 and 134.1 ± 7.6 ml, respectively), stroke volume (123.0 ± 7.9 and 96.0 ± 4.8 ml, respectively), cardiac output (20.2 ± 1.5 and 15.0 ± 1.3 liters·min–1, respectively) and oxygen uptake (42.1 ± 2.1 and 31.1 ± 2.4 ml·kg–1·min–1, respectively), while diastolic blood pressure (70.3 ± 5.6 and 77.5 ± 4.2 mm Hg, respectively) and total peripheral resistance [4.3 ± 0.8 and 5.9 ± 1.41 (dyn·s–1·cm–5)·10–1, respectively], were significantly (p < 0.05) lower. Conclusions: The present study suggests that the differences between trained and untrained elderly in absolute oxygen uptake of the working muscles and peak power output at maximal exercise test are due to physical activity status. The higher aerobic capacity in the trained elderly is related to increased cardiovascular function and to a lesser extent to increased muscle mitochondria concentration and capillarity. Although untrained elderly have reduced maximal oxygen uptake at peak aerobic exercise, intrinsic regulation of mitochondrial function does not seem to be significantly altered because of aging associated physical inactivity. Therefore, untrained elderly can partially compensate for their lower cardiac output by increasing oxygen extraction to levels comparable with those of trained elderly.
Effects of Icodextrin on Glycemic and Lipid Profiles in Diabetic Patients Undergoing Peritoneal Dialysis
Authors: Babazono Tetsuya , Nakamoto Hidetomo , Kasai Kenji , Kuriyama Satoru , Sugimoto Tokuichiro , Nakayama Masaaki , Hamada Chieko , Furuya Ryuichi , Hasegawa Hirofumi , Kasahara Masato , Moriishi Misaki , Tomo Tadashi , Miyazaki Masanobu , Sato Manaka , Yorioka Noriaki , Kawaguchi Yoshindo
Published: July 2007

Aim: Icodextrin reduces glucose absorption from the peritoneal dialysate. We conducted this prospective, open-labeled, multicenter study to determine the effects of icodextrin on glycemic and lipid parameters in diabetic patients undergoing continuous ambulatory peritoneal dialysis (PD) or automated PD. Methods: Patients were recruited from 15 institutions in Japan, and a total of 51 patients (15 women and 36 men, mean age: 59 ± 10 years, median duration of PD: 13 months) were enrolled. The patients were administered an overnight or daytime dwell of 1.5 or 2.0 l of 7.5% icodextrin-containing solution. At baseline and 3, 6, 9 and 12 months after the start of icodextrin, nonfasting blood was drawn for measurement of glycated hemoglobin (HbA1C) and serum lipids. Results: During icodextrin treatment, there was no change in overall HbA1C levels compared to baseline values; however, for those with baseline HbA1C ≧6.5% (n = 22), significant decreases in HbA1C were observed. Mean total/LDL cholesterol and triglycerides were decreased significantly during icodextrin treatment, with greater decreases for patients with baseline total cholesterol ≧220 mg/dl, LDL cholesterol ≧120 mg/dl or triglycerides ≧150 mg/dl. HDL cholesterol did not differ at any time point; however, values for patients with baseline HDL cholesterol <40 mg/dl tended to increase with marginal significance. Conclusions: In the current study, switching from glucose-containing dialysis solution to icodextrin resulted in improved lipid profiles and possibly a favorable metabolic profile, particularly in patients with poor glycemic control. These hypotheses remain to be proven in controlled clinical trials.
Heterogeneity of Ghrelin/Growth Hormone Secretagogue Receptors
Authors: Muccioli Giampiero , Baragli Alessandra , Granata Riccarda , Papotti Mauro , Ghigo Ezio
Published: July 2007

Ghrelin is a gastric polypeptide displaying strong GH-releasing activity by activation of the type 1a GH secretagogue receptor (GHS-R1a) located in the hypothalamus-pituitary axis. GHS-R1a is a G-protein-coupled receptor that, upon the binding of ghrelin or synthetic peptidyl and non-peptidyl ghrelin-mimetic agents known as GHS, preferentially couples to Gq, ultimately leading to increased intracellular calcium content. Beside the potent GH-releasing action, ghrelin and GHS influence food intake, gut motility, sleep, memory and behavior, glucose and lipid metabolism, cardiovascular performances, cell proliferation, immunological responses and reproduction. A growing body of evidence suggests that the cloned GHS-R1a alone cannot be the responsible for all these effects. The cloned GHS-R1b splice variant is apparently non-ghrelin/GHS-responsive, despite demonstration of expression in neoplastic tissues responsive to ghrelin not expressing GHS-R1a; GHS-R1a homologues sensitive to ghrelin are capable of interaction with GHS-R1b, forming heterodimeric species. Furthermore, GHS-R1a-deficient mice do not show evident abnormalities in growth and diet-induced obesity, suggesting the involvement of another receptor. Additional evidence of the existence of another receptor is that ghrelin and GHS do not always share the same biological activities and activate a variety of intracellular signalling systems besides Gq. The biological actions on the heart, adipose tissue, pancreas, cancer cells and brain shared by ghrelin and the non-acylated form of ghrelin (des-octanoyl ghrelin), which does not bind GHS-R1a, represent the best evidence for the existence of a still unknown, functionally active binding site for this family of molecules. Finally, located in the heart and blood vessels is the scavenger receptor CD36, involved in the endocytosis of the pro-atherogenic oxidized low-density lipoproteins, which is a pharmacologically and structurally distinct receptor for peptidyl GHS and not for ghrelin. This review highlights the most recently discovered features of GHS-R1a and the emerging evidence for a novel group of receptors that are not of the GHS1a type; these appear involved in the transduction of the multiple levels of information provided by GHS and ghrelin.
An Objective Method for Bed Capacity Planning in a Hospital Department
Authors: Six P. , Chaussalet T. , Antonioli D. , Lombrail P. , Beux P. Le , Nguyen J. M.
Published: July 2007

Objectives:
To propose an objective approach in order to determine the number of beds required for a hospital department by considering how recruitment fluctuates over time. To compare this approach with classical bed capacity planning techniques.

Methods:
Asimulated data-based evaluation of the impact that the variability in hospital department activity produces upon the performance of methods used for determining the number of beds required. The evaluation criteria included productive efficiency measured bythe bed occupancy rate, accessibility measured by the transfer rate of patients due to lack of available beds and a proxy of clinical effectiveness, by the proportion of days during which there is no possibility forunscheduled admission.

Results:
When the variability of the number of daily patients increases, the Target Occupancy Rate favors productive efficiency at the expense of accessibility and proxy clinical effectiveness. On the contrary, when the variability of the department activity is marginal, the Target Activity Rate penalizes the proxy of clinical effectiveness, and the Target Occupancy Rate under-optimizes productive efficiency.

The method we propose led to a superior performance in terms of accessibility and proxy of clinical effectiveness at the expense of productive efficiency. Such a situation is suitable for intensive care units. In the case of other departments, a weighting procedure should be used to improve productive efficiency.

Conclusions:
This approach could be considered as the first step of a family of methods for quantitative healthcare planning.
Dutch Virtual Integration of Healthcare Information
Authors: Vlug A. E. , van Boven G. J. , de Graaf J. C.
Published: July 2007

Objectives:
As information technology creates opportunities for cooperation which crosses the boundaries between healthcare institutions, it will become an integral part of the Dutch healthcare system. Along with manyinvolved organizationsin healthcare the National IT Institute for Healthcare in the Netherlands (NICTIZ) is working on the realization of a national IT infrastructure for healthcare and a national electronic patient record (EPR).

Methods:
An underlying national architecture is designed to enable the Dutch EPR virtually, not in a national database, nor on a patient’s smartcard. The required secure infrastructure provides generic functions for healthcare applications: patient identification, authentication and authorization of healthcare professionals.

Results:
The first national applications in the EPR program using a national index of where patient data is stored, are the electronic medication record and the electronic record for after hours GP services. The rollout of the electronic medication record and electronic record for after hours GP services has been started in 2007.

Conclusions:
To guarantee progress of electronic data exchange in healthcare in the Netherlands we have primarily opted for two healthcare applications: the electronic medication record and the electronic record for after hours GP services. The use of a national switchpoint containing the registry of where to find what information, guarantees thatthe professional receives the most recent information and omits large databases to contain downloaded data. Proper authorization, authentication as well as tracing bythe national switchpoint also ensures a secure environment for the communication of delicate information.
National Health IT Services in Finland
Authors: Ensio A. , Laine M. , Nykänen P. , Itkonen P. , Saranummi N.
Published: July 2007

Objectives:
In 2002 a decision was reached to set up a nation-wide electronic health record system in Finland. The legal framework of actors with the necessary mandate was approved in the parliament in December 2006. A set of standards and norms have been selected that all health care actors need to follow. Functional specifications of the services were completed in 2006. Setting up the centralized health IT services begins in 2007.

Centralization of patient record data allows the reorganization of health service providers to take place at local and regional levels according to need. The services allow users to access patient records securely from anywhere with the provision that they have the right to access private patient data.

Methods:
The functionality of the services and the necessary infrastructure has been agreed to in projects and working groups involving users, experts, key stakeholders and vendors.

Results:
The legal framework was approved in the parliament in December 2006. The functional specifications of thecentralized health IT services were finalized in 2006.

Conclusions:
The implementation of the services will start in 2007.
The Contributions of Culture and Ethnicity To New Zealand Mental Health Research Findings
Authors: Tapsell Rees , Mellsop Graham
Published: July 2007

Background & material: In the last five years a number of studies have been conducted in specialist psychiatric and primary care populations in New Zealand which have allowed comparisons in terms of clinical phenomena and therapeutic experiences between Mâori (the indigenous people of New Zealand) and non-Mâori. These studies were reviewed in terms of the methodology used, their major findings and their implications.

Discussion: In specialist psychiatric services Mâori were more likely to present with hallucinations and/or aggression and less likely to present with depression and/or episodes of self-harm. They were overly represented in those with schizophrenia. Mâori were more likely to be involved in acts of aggression and to be secluded, and an equivalent episode of care for Mâori appeared to be significantly more costly than for non Mâori. Other studies, conducted in prison and community-based samples, suggested that Mâori were less likely to access care and, when given a diagnosis of depression, less likely to be prescribed anti-depressant medication. The rates of depression were significantly higher in Mâori (women) and Mâori were also overly represented in those with anxiety and substance misuse disorders. These differences remained even after the sample was standardised for socio-economic status. Further exploration of the genesis and implications of these findings, derived from a strong and relatively well-defined indigenous people, may usefully inform the more general issues of culture and its significance for diagnosis, classification and service use.

Conclusions: While the methodologies used and the actual results gained differed across studies, there do seem to be differences in phenomenological profiles at presentation, in the diagnostic patterns, the cost of care, and the therapeutic experiences between Mâori and non-Mâori New Zealanders. These differences may reflect actual differences between certain ethnic groups, which then explain the differences in the experiences of those users, or they may reflect inadequacies on the parts of non-Mâori clinicians, their diagnostic tools and the services in which they operate, in catering for Mâori patients.
Acculturation and Mental Health Among Ghanaians in the Netherlands
Authors: Knipscheer Jeroen W. , Kleber Rolf J.
Published: July 2007

Background: The current literature on the relationship between cultural adaptation and mental health is premature to offer a comprehensive explanation about the ways acculturation exerts either positive or adverse effects on the mental health of migrants.

Aim: This study is an empirical approach towards understanding the magnitude of the relationship between consequences of cultural adaptation and psychological distress.

Methods: Two samples of Ghanaian migrants in the Netherlands were included: a clinical group ( n = 36) and a non-clinical community group ( n = 97). Data were acquired by administering a semi-structured interview. Quantified data were analysed using multivariate techniques.

Results: Contradictory to our hypotheses, the reported level of mental health symptoms in both groups was relatively low, suggesting a substantial resilience among the Ghanaian group. Confirming our hypotheses, specific dimensions of the acculturation process were associated with health status, particularly affiliation with cultural traditions and feelings of loss concerning the country of birth.

Conclusions: Acculturation demands capture critical elements of migrants' experiences that warrant professional interventions tailored to their specific needs. A subtle balance between holding on to the supportive cultural traditions together with moderate involvement in ruminating about pre-migration life, in conjunction with acquiring instrumental skills of the host culture, is a starting position for better health.
Script Analysis of the Hunting Process of Serial Sex Offenders
Authors: Beauregard Eric , Proulx Jean , Rossmo Kim , Leclerc Benoît , Allaire Jean-François
Published: July 2007

This study identified hunting process scripts in a sample of 361 serial sex crimes committed by 72 serial sex offenders, using multiple correspondence analysis and hierarchical cluster analysis. Three hunting process scripts that take into account both behavioral and geographic aspects of crime were identified. These three scripts included different tracks of the hunting process. The coercive script includes the home-intrusion rape track and the outdoor rape track. The manipulative script includes the sophisticated rape track and the family-infiltrator rape track. The nonpersuasive script includes only the direct action rape track. The theoretical relevance of these three scripts and their practical implications for crime prevention strategies and geographic profiling are discussed.
A Comparison of Unresolved versus Resolved Status and its Relationship to Behaviour in Maltreated Adolescents
Authors: Webster Linda , Hackett Rachelle Kisst
Published: July 2007

This exploratory investigation sought both to gain a better understanding of the mental representations of attachment in high-risk, maltreated adolescents and to explain how, if at all, unresolved attachment representations are related to behavioural maladjustment. Parent ratings, self-report ratings and attachment state of mind were obtained from 34 adolescents with a history of maltreatment. Results showed that maltreated adolescents with unresolved states of mind in regard to attachment were rated higher on maladaptive behaviour and lower on adaptive behaviour than maltreated adolescents who were resolved. Implications for school-based mental health intervention and future research are discussed.
Sacrificial pasts and messianic futures
Authors: Fox Christopher A.
Published: July 2007

Religion has become a vital resource for attempts to rethink the meaning of the political. This article rehearses the efforts of two recent figures, René Girard and Giorgio Agamben, to transform the political by renewing its connection to religion. Both thinkers struggle to escape politics as defined by Carl Schmitt's friend/enemy distinction. Girard and Agamben do clash ideologically, but their inquiries into sacrifice and messianism take similar courses. Regarding origins, Girard argues for the sacrificial crisis as the common parent to religion and politics. Conversely, for Agamben, the Roman figure of homo sacer distinguishes politics from religion. With respect to the future, Girard's messianism installs Christian belief as the only way to move beyond violence. By contrast, Agamben steers Pauline messianism toward the efforts to displace sovereignty and reopen the political. I conclude that Agamben breaks with Schmitt while Girard reinscribes his politics at a higher level.
The inner experience of living matter
Authors: Sørensen Asger
Published: July 2007

The dialectical aspect in the work of Georges Bataille is often neglected. At the suggestion of Foucault and Derrida, Bataille is most often even taken to be a non-dialectical thinker. But Bataille worked intensely with Hegel's ideas, his thought was expressed in Hegelian terms, and both his epistemology and his ontology can be considered a determinate negation of Hegel's position in the Phenomenology. This is shown, first, by analysing Bataille's notions of `inner experience', and, second, by showing how Bataille extends dialectics to the natural, non-human realm, and even conceives the link between the human and non-human as itself dialectical. However, once we see the dialectical nature of his theoretical stance, we are struck by a great vagueness in his practical conception of where society ought to be going.