bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesteryl ester transfer protein (CETP) increases postprandial triglyceridaemia and delays triacylglycerol plasma clearance in transgenic mice
Authors: Salerno Alessandro G. , Patrício Patrícia R. , Berti Jairo A. , Oliveira Helena C. F. 
Published: February 2009

The CETP (cholesteryl ester transfer protein) is a plasma protein synthesized in several tissues, mainly in the liver; CETP reduces plasma HDL (high-density lipoprotein) cholesterol and increases the risk of atherosclerosis. The effect of CETP levels on postprandial intravascular metabolism of TAGs (triacylglycerols) is an often-overlooked aspect of the relationship between CETP and lipoprotein metabolism. Here, we tested the hypothesis that CETP delays the plasma clearance of TAG-rich lipoprotein by comparing human CETP expressing Tg (transgenic) and non-Tg mice. After an oral fat load, the postprandial triglyceridaemia curve was markedly increased in CETP-Tg compared with non-Tg mice (280±30 versus 190±20 mg/dl per 6 h respectively, P&lt;0.02). No differences in intestinal fat absorption and VLDL (very-low-density lipoprotein) secretion rates were observed. Kinetic studies of double-labelled chylomicron-like EMs (emulsions) showed that both [3H]triolein and [14C]cholesteryl oleate FCRs (fractional clearance rates) were significantly reduced (∼20%) in CETP-Tg mice. Furthermore, TAG from lipid EM pre-incubated with CETP-Tg plasma had plasma clearance and liver uptake significantly lower than the non-Tg plasma-treated lipid EM. In addition, reductions in post-heparin plasma LPL (lipoprotein lipase) activity (50%) and adipose tissue mRNA abundance (39%) were verified in CETP-Tg mice. Therefore we conclude that CETP expression in Tg mice delays plasma clearance and liver uptake of TAG-rich lipoproteins by two mechanisms: (i) transferring TAG to HDLs and increasing CE content of the remnant particles and (ii) by diminishing LPL expression. These findings show that the level of CETP expression can influence the responsiveness to dietary fat and may lead to fat intolerance.
Improvement of survival in sex cord stromal tumors – an observational study with more than 25 years follow‐up
Authors: HÖLSCHER GABRIELE , ANTHUBER CHRISTOPH , BASTERT GUNTHER , BURGES ALEXANDER , MAYR DORIS , OBERLECHNER ERNST , SCHUBERT‐FRITSCHLE GABRIELE , SINZ SONJA , SOMMER HARALD , SCHMALFELDT BARBARA , ENGEL JUTTA ,   FOR THE PROJECT GROUP ‘MALIGNANT OVARIAN TUMORS’ OF THE MUNICH CANCER CENTER (MCC)
Published: February 2009

AbstractObjective. To highlight aspects of malignant ovarian sex cord stromal tumors, effects of treatment, and developments over the past 28 years. Design. Population‐based cohort study. Setting. Gynecological departments within the catchment‐area of the Munich Cancer Registry and associated with the project group ‘Malignant Ovarian Tumors’ of the Munich Cancer Center. Sample. One hundred and forty‐five women with an invasive single sex cord stromal tumor diagnosed between 1978 and 2005. Methods. Overall survival was estimated with the Kaplan–Meier method, relative survival was computed by the ratio of observed to expected survival rate. The impact of age, International Federation of Gynecology and Obstetrics (FIGO)‐stage, residual tumor, and chemotherapy was examined by multivariate analysis (Cox regression model). Main outcome measures. Overall and relative survival and multivariate adjusted overall survival. Results. Survival data showed a five‐/10‐year overall survival of 55.8%/42.8% (relative survival 58.6%/49.2%) for women diagnosed before 1988 and 89.1%/78.3% (relative survival 92.7%/85.2%) for women diagnosed after 1988. After adjustment for age and FIGO‐stage, the following hazard ratios and 95% confidence intervals (95% CI) for treatment methods resulted: 3.3 (95% CI 1.5–7.0) for women with compared to women without residual tumor and 2.2 (95% CI 1.2–4.2) for women with chemotherapy compared to women where no chemotherapy was given. Conclusions. Improvements in survival may be attributed to a stage‐shift toward more favorable stages at diagnosis and to advances in treatment such as improved surgery without residual tumor. There is no evidence for any benefit of adjuvant chemotherapy. Surgery remains the cornerstone of treatment, yet the benefit of postoperative therapy is still under debate.
Perinatal risk factors in young adult‐onset type 1 and type 2 diabetes – a population‐based case‐control study
Authors: LAMMI NIINA , BLOMSTEDT PAUL A. , MOLTCHANOVA ELENA , ERIKSSON JOHAN G. , TUOMILEHTO JAAKKO , KARVONEN MARJATTA 
Published: February 2009

AbstractObjective. To examine the effects of the size of the mother and the newborn, including placental weight and gestational age at delivery, on the risk for young adult‐onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM). Design. Case‐control study. Setting. Finland. Population. Subjects with T1DM and T2DM aged 15–39 at diagnosis between the years 1992 and 1996. The number of case‐control pairs was 858 for T1DM and 355 for T2DM. Methods. Diabetic subjects were identified from the Finnish national healthcare registers and reports from diabetes nurses. Control subjects were obtained from the population register. Data on perinatal factors were obtained from the original healthcare records. The odds ratios (ORs) for both types of diabetes were estimated using conditional logistic regression. Results. The risk for early‐onset T2DM decreased with increasing birthweight until 4.2 kg (OR 0.49 (95% confidence interval 0.37–0.66) per 1 kg), but with birthweight above 4.2 kg the risk increased (OR 4.8 (1.3–17.6) per 1 kg). The risk for T2DM decreased also with increasing birth length (OR 0.88 (0.81–0.95) per 1 cm), body mass index at birth (OR 0.81 (0.73–0.90) per 1 kg/m2), and placental weight (OR 0.77 (0.61–0.98) per 100 g). The latter was not significant when adjusted for birthweight. The examined perinatal factors did not affect the risk for T1DM in young adults. Conclusions. Birth size significantly affects the risk for T2DM diagnosed in young adulthood but no evidence was found of an association between late‐onset T1DM and perinatal factors.
Systems biology metabolic modeling assistant: an ontology-based tool for the integration of metabolic data in kinetic modeling
Authors: Reyes-Palomares Armando , Montañez Raul , Real-Chicharro Alejando , Chniber Othmane , Kerzazi Amine , Navas-Delgado Ismael , Medina Miguel Ángel , Aldana-Montes José F. , Sánchez-Jiménez Francisca 
Published: February 2009

Abstract
Summary: We present Systems Biology Metabolic Modeling Assistant (SBMM Assistant), a tool built using an ontology-based mediator, and designed to facilitate metabolic modeling through the integration of data from repositories that contain valuable metabolic information. This software can be used for the visualization, design and management of metabolic networks; selection, integration and storage of metabolic information; and as an assistant for kinetic modeling.
Availability: SBMM Assistant for academic use is freely available at http://www.sbmm.uma.es.
Contact: kika@uma.es
Prognostic value of plasma midregional pro‐adrenomedullin and C‐terminal‐pro‐endothelin‐1 in chronic heart failure outpatients
Authors: Adlbrecht Christopher , Hülsmann Martin , Strunk Guido , Berger Rudolf , Mörtl Deddo , Struck Joachim , Morgenthaler Nils G. , Bergmann Andreas , Jakowitsch Johannes , Maurer Gerald , Lang Irene M. , Pacher Richard 
Published: February 2009

AimsThe identification of chronic heart failure (CHF) patients at high risk of adverse outcome remains a challenge. New peptides are emerging that may give additional information. In CHF patients, endothelin (ET) levels predict mortality risk. Adrenomedullin has been shown to predict mortality in ischaemic heart failure, but not in unselected or non‐ischaemic CHF patients. Moreover, ADM and ET have never been assessed in one model. The aim of the present study was to assess the prognostic value of midregional‐pro‐adrenomedullin (MR‐proADM) and C‐terminal‐pro‐endothelin‐1 (CT‐proET‐1) in outpatients with CHF.Methods and resultsWe measured plasma MR‐proADM and CT‐proET‐1 levels in 786 consecutive CHF outpatients and compared them with B‐type natriuretic peptide (BNP) levels. At 24‐month follow‐up, 233 patients had died. A stepwise forward Cox regression model with age, sex, estimated glomerular filtration rate, NYHA > II, left ventricular ejection fraction (LVEF), MR‐proADM, CT‐proET‐1, and BNP as possible predictors revealed that MR‐proADM levels [hazard ratio (HR) = 1.77, P < 0.001] in addition to age (HR = 1.02, P = 0.004), ejection fraction (HR = 0.98, P = 0.004), and NYHA > II (HR = 1.86, P < 0.001) were predictors of death at 24 months. When the analysis was repeated dependent on NYHA‐stage, MR‐proADM (HR = 2.12, P < 0.001) and LVEF (HR = 0.96, P = 0.006) were significant markers, but only in patients with mild/moderate CHF.ConclusionOur data suggest that MR‐proADM may be an important prognostic humoral marker, especially in mild/moderately symptomatic and non‐ischaemic CHF patients.
Pathophysiological and clinical relevance of simplified monitoring of nocturnal breathing disorders in heart failure patients
Authors: Pinna Gian Domenico , Maestri Roberto , Mortara Andrea , Johnson Paul , Andrews David , Ponikowski Piotr , Witkowski Tomasz , Robbi Elena , La Rovere Maria Teresa , Sleight Peter 
Published: February 2009

AimsNocturnal breathing disorders in the form of periodic breathing (PB) are very common in heart failure (HF) patients. There is an increasing interest in simple and affordable tools to screen patients and monitor these disorders at home on a long‐term basis. We aimed to assess the pathophysiological and clinical relevance of a simplified method for monitoring of PB suitable to be self‐managed by the patient at home.Methods and resultsA night‐time respiratory recording was performed in 397 optimally treated HF patients (age 60 ± 11 years, NYHA class 2.4 ± 0.6, left ventricular ejection fraction 29 ± 7%) and the duration of PB (PBDur) automatically computed. Patients were followed‐up for 1 year and the prognostic value of PBDur evaluated. In 45 patients, we assessed the association between PBDur and severity of oxygen desaturations (number of desaturations >3%). Twenty six of the 397 patients died of cardiac causes. A PBDur ≥2 h was significantly associated with an increased risk of cardiac death after adjustment for major clinical predictors [hazard ratio (95% CI): 3.5 (1.6–7.9), P = 0.002]. The correlation between PBDur and severity of desaturations was 0.94 (P < 0.0001).ConclusionRelevant pathophysiological and clinical information can be obtained from simplified monitoring of breathing disorders managed by the patient. These results provide new perspectives in the investigation of the clinical impact of abnormal breathing in HF patients.
Effect of Enzymatic Tempering of Wheat Kernels on Milling and Baking Performance
Authors: Yoo J. , Lamsal B. P. , Haque E. , Faubion J. M. 
Published: February 2009

ABSTRACTThis study examined the effect of cell‐wall‐degrading enzymes added to temper water on wheat milling performance and flour quality. An enzyme cocktail consisting of cellulase, xylanase, and pectinase and five independent variables (enzyme concentration, incubation time, incubation temperature, tempered wheat moisture content, and tempering water pH) were manipulated in a response surface methodology (RSM) central composite design. A single pure cultivar of hard red winter wheat was tempered under defined conditions and milled on a Ross experimental laboratory mill. Some treatment combinations affected flour yield from the break rolls more than that from the reduction rolls. However, a maximum for flour yield was not found in the range of parameters studied. Though treatments did not affect the optimum water absorption for breadmaking, enzyme‐treated flours produced dough exhibiting shorter mixing times and slack and sticky textures compared with the control. Regardless of differences in mixing times, specific loaf volumes were not significantly different among treatments. Crumb firmness of bread baked with flour milled from enzyme‐treated wheat was comparable to the control after 1 day but became firmer during storage up to 5 days.
Pilot study on photodynamic therapy for acne using indocyanine green and diode laser
Authors: KIM Beom Joon , LEE Ho Gyun , WOO Seung Man , YOUN Jai Il , SUH Dae Hun 
Published: February 2009

ABSTRACTTo demonstrate the efficacy of photodynamic therapy using indocyanine green (ICG) dye with a diode laser for acne treatment of Asian subjects, an analysis was performed of 16 randomly chosen Korean patients with acne vulgaris treated by photodynamic therapy for a mean follow up of 2 months. Volunteers were divided into two groups, a single‐ and multiple‐treatment group, in which photodynamic therapy was repeated three times with 1‐week intervals. Photodynamic therapy using ICG dye with a diode laser was effective for acne treatment of Korean subjects. However, multiple treatments were not superior to single treatments in controlling acne lesions. Photodynamic therapy combined with ICG dye and diode laser might be an alternative treatment modality for acne in Asian subjects.
Cutaneous complications among i.v. buprenorphine users
Authors: HO Roger C. M. , HO Emily C. L. , MAK Anselm 
Published: February 2009

ABSTRACTi.v. buprenorphine hydrochloride (Subutex) misuse has been creating a number of medical complications, and cutaneous manifestations such as soft tissue infection are one of the commonest consequences. Between January 2004 and December 2006, amongst 130 i.v. buprenorphine abusers who presented to the National University Hospital, Singapore, cutaneous complications were identified in 45 patients (prevalence, 31%) with cellulitis and skin abscess being the commonest complications. Tissue and blood culture were positive in 19 (42%) patients and Methicillin‐sensitive Staphylococcus aureuswas the commonest microbiological isolate (20%). Univariate linear regression revealed significant relationships between body temperature (P = 0.03), heart rate (P = 0.02), respiratory rate (P < 0.001), total peripheral white cell count (P = 0.011), absolute neutrophil count (P < 0.001) and serum C‐reactive protein (CRP) level (P < 0.001) on admission and through the duration of hospitalization. In multivariate analysis, respiratory rate on admission remained significantly associated with longer duration of hospitalization (P = 0.01). i.v. cloxacillin, i.v. crystallized penicillin and oral cloxacillin were the most commonly prescribed antibiotics while 11 (24%) patients required surgical treatment. The mean duration of hospitalization was 8 ± 11 days and repeated cutaneous complications occurred in eight (18%) patients. In conclusion, cutaneous complications are common among i.v. buprenorphine users. Respiratory rates on admission predict duration of hospital stay. A high index of suspicion coupled with a correct choice of antibiotics based on local bacteriological surveillance is necessary in an attempt to reduce cutaneous complications and length of hospitalization.
Evaluation of the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system in elderly patients with pressure sores undergoing fasciocutaneous flap‐reconstruction
Authors: MIZUMOTO Kazuo , MORITA Eishin 
Published: February 2009

ABSTRACTThe aim of the present study was to predict operative morbidity in elderly patients with deep pressure sores by using the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system. Fifteen patients over 70 years old were retrospectively reviewed who had undergone gluteus maximus fasciocutaneous flap‐reconstruction for pressure sores of the sacral region from 1 April 2005 to 31 March 2007. Complications were seen in six cases (40%) after operation. Four were wound infection, one was chest infection and another was septicemia. The subjects were divided into two groups by the presence (complicated group) or absence (non‐complicated group) of postoperative complications. Each item of physiological scores, physiological score (PS), operative severity score (OS) and predicted morbidity rate (R) were calculated and compared between two groups. As a result, hemoglobin (P = 0.0276), PS (P = 0.0023) and R (P = 0.0078) differed significantly between the two groups. It is noteworthy that the PS were over 25 in all of the complicated group, but in only one of nine in the non‐complicated group (P = 0.0014). Our study suggests that, for pressure sores in the sacral region in elderly patients, gluteus maximus fasciocutaneous flap‐reconstruction can be employed in patients whose PS are under 24 in the POSSUM scoring system.
Neuroendocrine stimulatory tests of hypothalamus–pituitary–adrenal axis in psoriasis and correlative implications with psychopathological and immune parameters
Authors: KARANIKAS Evangelos , HARSOULIS Faidon , GIOUZEPAS Ioannis , GRIVEAS Ioannis , CHRISOMALLIS Fotios 
Published: February 2009

ABSTRACTPsoriasis constitutes one of the most representative examples of psychosomatic disorders. The published work investigating the psychological parameters and the way they interact during the course of the disease is extensive, whereas only a few studies have focused on the neuroendocrine framework of psoriasis. In the present study, the objective was to investigate the neuroendocrine parameters of psoriasis and the way they interact with psychopathological and immune variables. Patients with psoriasis (n = 24) and the same number of matched healthy controls underwent psychiatric evaluation with interviews and psychometric questionnaires. Both of the groups underwent the corticotropin‐releasing hormone (CRH) test and the dexamethasone suppression test (DST) to investigate functional parameters of the hypothalamus–pituitary–adrenal (HPA) axis. The evaluation of immune variables included the estimation of the distribution of T‐cell and natural killer lymphocytes. Levels of depressive and anxiety features were increased within subjects with psoriasis and they were significantly correlated with stressful life events and the extent of the disease. The adrenocorticotrophic hormone and cortisol levels increased after CRH infusion without significant differences between the two groups and the psoriatic subjects’ cortisol suppression after DST was within normal range, though relatively blunted. No significant correlations were identified among neuroendocrine, psychopathological and immune parameters. No particular neuroendocrine profile has been identified among psoriatic patients and the hypothesized interaction with psychopathological and immune parameters was not replicated. Nevertheless, it is still premature to exclude the possibility that a subtle latent alteration of the HPA axis function might exist, in psoriasis, either stemming from the psychopathology or from the disease per se.
Effects ofSchisandra sphenantheraextract on the pharmacokinetics of midazolam in healthy volunteers
Authors: Xin Hua‐Wen , Wu Xiao‐Chun , Li Qing , Yu Ai‐Rong , Xiong Lei 
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Schisandra sphenantheraextract (SchE) and tacrolimus are often co‐administered in treating renal and liver transplant recipients in China.• Our previous study has demonstrated that SchE can increase the oral bioavailability of tacrolimus.WHAT THIS STUDY ADDS• The results of this study show that SchE can markedly increase the blood concentration and oral bioavailability of midazolam in healthy volunteers.• This finding suggests that SchE may be an inhibitor of CYP3A and is likely to alter the disposition of drugs that are metabolized by CYP3A.AIMSTo assess the effect ofSchisandra sphenantheraextract (SchE) on the pharmacokinetics of midazolam, a probe drug of CYP3A, and its metabolite 1′‐hydroxy midazolam in healthy volunteers.METHODSTwelve healthy male volunteers were orally treated with SchE, three capsules twice daily for 7 days. Pharmacokinetic investigations of oral midazolam administration at 15 mg were performed both before and at the end of the SchE treatment period. The plasma midazolam and 1′‐hydroxy midazolam concentrations were determined by high‐performance liquid chromatography–tandem mass spectrometry. Estimated pharmacokinetic parameters before and with SchE were calculated with noncompartmental techniques.RESULTSFollowing administration of SchE, the average increases (%) of individual increases in AUC, AUMC andCmaxof midazolam were 119.4% [95% confidence interval (CI) 83.9, 155.0], 183.4% (95% CI 120.5, 246.2) and 85.6% (95% CI 14.4, 156.9), respectively (P< 0.01 or 0.05). On average, there was a 133.3% (95% CI 8.9, 257.7) increase in midazolamtmax(P< 0.01). The average decrease (%) in CL/Fwas 52.1% (95% CI 44.9, 59.4) (P< 0.01). No significant changes were seen in midazolam half‐life. After co‐administration of SchE, the average increase (%) intmaxof 1′‐hydroxy midazolam was 150.0% (95% CI 22.2, 277.8) (P< 0.05). No significant differences were observed in the other pharmacokinetic parameters of 1′‐hydroxy midazolam.CONCLUSIONSSchE can markedly increase the oral bioavailability of midazolam in healthy volunteers. SchE is an inhibitor of CYP3A and has a high susceptibility to alter the disposition of drugs metabolized by CYP3A.
In vitroandin vivoglucuronidation of midazolam in humans
Authors: Hyland Ruth , Osborne Toby , Payne Anthony , Kempshall Sarah , Logan Y. Raj , Ezzeddine Khaled , Jones Barry 
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Midazolam is extensively metabolized and is eliminated in urine predominantly as conjugates of 1′‐hydroxymidazolam.• Midazolam is known to undergo N‐glucuronidationin vitroby UGT1A4.• In vitro1′‐hydroxymidazolam is O‐glucuronidated by UGT2B4 and UGT2B7, and N‐glucuronidated by UGT1A4.WHAT THIS STUDY ADDS• N‐glucuronide of midazolam has been quantified in human urine, indicating for the first time that this route of metabolism occursin vivo.• Metabolism of 4‐hydroxymidazolam has been compared with that of 1′‐hydroxymidazolamin vitro.• This study provides further evidence,in vitroandin vivo, of the importance of N‐glucuronidation in the metabolism of midazolam and its metabolites.AIMSMidazolam (MDZ) is a benzodiazepine used as a CYP3A4 probe in clinical andin vitrostudies. A glucuronide metabolite of MDZ has been identifiedin vitroin human liver microsome (HLM) incubations. The primary aim of this study was to understand thein vivorelevance of this pathway.METHODSAn authentic standard of N‐glucuronide was generated from microsomal incubations and isolated using solid‐phase extraction. The structure was confirmed using proton nuclear magnetic resonance (NMR) and1H‐13C long range correlation experiments. The metabolite was quantifiedin vivoin human urine samples. Enzyme kinetic behaviour of the pathway was investigated in HLM and recombinant UGT (rUGT) enzymes. Additionally, preliminary experiments were performed with 1′‐OH midazolam (1′‐OH MDZ) and 4‐OH‐midazolam (4‐OH MDZ) to investigate N‐glucuronidation.RESULTSNMR data confirmed conjugation of midazolam N‐glucuronide (MDZG) standard to be on the α‐nitrogen of the imidazole ring.In vivo, MDZG in the urine accounted for 1–2% of the administered dose.In vitroincubations confirmed UGT1A4 as the enzyme of interest. The pathway exhibited atypical kinetics and a substrate inhibitory cooperative binding model was applied to determineKm(46 µM, 64 µM),Vmax(445 pmol min−1 mg−1, 427 pmol min−1 mg−1) andKi(58 µM, 79 µM) in HLM and rUGT1A4, respectively. From incubations with HLM and rUGT enzymes, N‐glucuronidation of 1′‐OH MDZ and 4‐OH MDZ is also inferred.CONCLUSIONSA more complete picture of MDZ metabolism and the enzymes involved has been elucidated. Direct N‐glucuronidation of MDZ occursin vivo. Pharmacokinetic modelling using Simcyp™ illustrates an increased role for UGT1A4 under CYP3A inhibited conditions.