bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study
Authors: ASAHINA Akihiko , NAKAGAWA Hidemi , ETOH Takafumi , OHTSUKI Mamitaro ,   THE ADALIMUMAB M04‐688 STUDY GROUP
Published: February 2010

AbstractIncidence of psoriasis vulgaris in Asians is estimated at 0.05–0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G1 monoclonal antibody, was efficacious and well‐tolerated in patients with chronic plaque psoriasis. This 24‐week, placebo‐controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80‐mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40‐mg eow plus loading dose and 80‐mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection‐site reactions and hepatic events occurred in greater percentages of adalimumab‐treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80‐mg loading dose in the treatment of psoriasis.
From anti‐p200 pemphigoid to anti‐laminin γ1 pemphigoid
Authors: DAINICHI Teruki , KOGA Hiroshi , TSUJI Takako , ISHII Norito , OHYAMA Bungo , UEDA Akihiro , NATSUAKI Yohei , KARASHIMA Tadashi , NAKAMA Takekuni , YASUMOTO Shinichiro , ZILLIKENS Detlef , HASHIMOTO Takashi 
Published: February 2010

AbstractAnti‐laminin γ1 pemphigoid is an autoimmune subepidermal bullous disease first described in 1996, and has been distinct from previously known subepidermal blistering diseases, such as bullous pemphigoid and epidermolysis bullosa acquisita. Circulating autoantibodies of the patients do not react to any known autoantigen of the skin, but react to a 200‐kDa molecule (p200) from dermal extracts. The identity of p200 was unmasked as laminin γ1, an extracellular matrix glycoprotein composing several forms of laminin heterotrimers. We renamed this disease from the previously used anti‐p200 pemphigoid to anti‐laminin γ1 pemphigoid, a new entity of an autoimmune bullous disease. In this decade, we have experienced over 70 cases of this disease. Although the number of the cases of anti‐laminin γ1 pemphigoid is half as many as the number of definitely diagnosed cases of epidermolysis bullosa acquisita in the same duration, a considerable number of the cases could be clinically misdiagnosed as epidermolysis bullosa acquisita. Unveiling the pathogenicity and development of a useful diagnostic method is necessary for appropriate management of this new disease.
Pretibial dystrophic epidermolysis bullosa with localized cutaneous amyloidosis: Coincidental or secondary amyloidosis?
Authors: AOKI Mikako , NIIMI Yayoi , ISHIKO Akira , KAWANA Seiji 
Published: February 2010

AbstractHere, we describe the case of a patient with pretibial dystrophic epidermolysis bullosa (PDEB) with amyloid deposition. The patient was a 40‐year‐old Japanese woman who presented a blistering eruption in the pretibial area with flat violaceous‐brown lichenoid papules. The histology of the blister revealed a subepidermal bulla with antibodies bound to basement membrane antigens on the blister roof by immunoflourescent mapping. Electron microscopy revealed a blister cleavage plane below the lamina densa. The histology of the lichenoid papules showed amyloid deposition in the papillary dermis. Because it was confined to just beneath the bulla base of the blister specimen, the amyloid deposition may have been derived from degenerated keratinocytes induced by damage to the epidermal–dermal junction due to blister formation in PDEB in this case. PDEB, in general, is often misdiagnosed as lichen amyloidosis; however, some PDEB cases could actually be associated with amyloid deposition.
What’s new in i.v. immunoglobulin therapy and pemphigus: High‐dose i.v. immunoglobulin therapy and its mode of action for treatment of pemphigus
Authors: AOYAMA Yumi 
Published: February 2010

AbstractHigh‐dose i.v. immunoglobulin (HD‐IVIG) has several distinguishing therapeutic characteristics including rapid clearance of pathogenic antibody, non‐immunosuppressive and less adverse effects. In 2009, the first multicenter, randomized, placebo‐controlled, double‐blind trial of HD‐IVIG for pemphigus was conducted in Japan. This clinical trial has proved that 400 mg/kg per day for 5 days administration of IVIG is effective as an adjuvant therapy with systemic steroid therapy and/or immunosuppressive agents. Among the several mechanisms to explain the mode of action of IVIG, several lines of evidence have suggested that neonatal Fc receptor for immunoglobulin (Ig)G (FcRn) plays an important role for rapid clearance of pathogenic antibody in pemphigus induced by HD‐IVIG. Additionally, the long suppression of IgG production induced by HD‐IVIG has been observed in some cases. Taking these characteristics into consideration, HD‐IVIG, which leads to decreased pathogenic IgG, is recommended to use in combination with oral corticosteroids or other immunosuppressants, which suppress the production of pathogenic IgG. This review summerizes experimental and clinical evidences for major mechanism of action in HD‐ IVIG and how to use it.
Immunoglobulin A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in a patient with atypical bullous pemphigoid
Authors: YAMAKI Fumi , MAYUZUMI Nobuyasu , IKEDA Shigaku , HASHIMOTO Takashi 
Published: February 2010

AbstractBullous pemphigoid is an autoimmune subepidermal blistering disease associated with autoantibodies against BP180 and BP230. We report herein a rare case of bullous pemphigoid with newly formed annular erythematous lesions when bullous skin lesions were in remission. Various immunological studies revealed immunoglobulin (Ig)A antibodies against desmoglein 1, envoplakin, periplakin and BP230 in addition to IgG antibodies against BP180 and BP230. These clinical and immunological changes in a patient are a rare event, suggesting an epitope‐spreading phenomenon.
Influence ofColophospermum mopanecanopy cover on litter decomposition and nutrient dynamics in a semi‐arid African savannah
Authors: Mlambo Donald , Mwenje Eddie 
Published: February 2010

AbstractThe objective of this study was to investigate the influence of mopane canopy cover on litter decomposition in a semi‐arid African savannah. We used a randomized block design with five blocks of 100 × 100 m demarcated in a 10‐ha pocket of open mopane woodland. Litterbags were placed beneath large (8.3 m crown diameter) and small mopane trees (2.7 m crown diameter) and in the intercanopy area. Decomposition was fastest in the intercanopy area exposed to solar radiation (k = 0.35 year−1), intermediate beneath small trees (k = 0.28 year−1) and slowest beneath large trees (k = 0.23 year−1). Soil temperatures beneath small and large trees were 3–5 and 6–9°C lower than in the intercanopy area, respectively. Bacterial and fungal counts were significantly higher (P < 0.05) beneath large than small trees and in the intercanopy area. The amount of N and P released did not vary significantly among sampling sites. Soil moisture in the dry season was similar among sampling sites but rainy‐season soil moisture was significantly greater (P < 0.05) beneath large than small trees and in the intecanopy area. Mopane canopy cover retarded litter decomposition suggesting that photodegradation could be an important factor controlling carbon turnover in semi‐arid African savannahs.
Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone
Authors: Grönlund Juha , Saari Teijo I. , Hagelberg Nora M. , Neuvonen Pertti J. , Olkkola Klaus T. , Laine Kari 
Published: February 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Oxycodone is an opioid analgesic that is metabolized mainly in the liver by cytochrome P450 (CYP) 2D6 and 3A4 enzymes.• So far, the effects of CYP2D6 or CYP3A4 inhibitors on the pharmacokinetics of oxycodone in humans have not been systematically studied. WHAT THIS STUDY ADDS • Drug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone.• When both of CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially.AIMThe aim of this study was to find out whether the inhibition of cytochrome P450 2D6 (CYP2D6) with paroxetine or concomitant inhibition of CYP2D6 and CYP3A4 with paroxetine and itraconazole, altered the pharmacokinetics and pharmacological response of orally administered oxycodone.METHODSA randomized placebo‐controlled cross‐over study design with three phases was used. Eleven healthy subjects ingested 10 mg of oral immediate release oxycodone on the fourth day of pre‐treatment with either placebo, paroxetine (20 mg once daily) or paroxetine (20 mg once daily) and itraconazole (200 mg once daily) for 5 days. The plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 h, and pharmacological (analgesic and behavioural) effects were evaluated.RESULTSParoxetine alone reduced the area under concentration–time curve (AUC(0,0–48 h)) of the CYP2D6 dependent metabolite oxymorphone by 44% (P < 0.05), but had no significant effects on the plasma concentrations of oxycodone or its pharmacological effects when compared with the placebo phase. When both oxidative pathways of the metabolism of oxycodone were inhibited with paroxetine and itraconazole, the mean AUC(0,∞) of oxycodone increased by 2.9‐fold (P < 0.001), and its Cmax by 1.8‐fold (P < 0.001). Visual analogue scores for subjective drug effects, drowsiness and deterioration of performance were slightly increased (P < 0.05) after paroxetine + itraconazole pre‐treatment when compared with placebo.CONCLUSIONSDrug interactions arising from CYP2D6 inhibition most likely have minor clinical importance for oral oxycodone if the function of the CYP3A4 pathway is normal. When both CYP2D6 and CYP3A4 pathways are inhibited, the exposure to oral oxycodone is increased substantially.
Oversight: a retrospective study of biochemical monitoring in patients beginning antihypertensive drug treatment in primary care
Authors: Coleman Jamie J. , McDowell Sarah E. , Evans Stephen J. W. , Gill Paramjit S. , Ferner Robin E. 
Published: February 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Guidelines recommend biochemical monitoring of patients treated with antihypertensive agents, although there is little primary evidence for these recommendations. WHAT THIS STUDY ADDS • Patients treated for hypertension in general practice often have no biochemical tests before, or in the 6 months after, starting drug treatment.AIMSGuidelines on the management of hypertension have recommended baseline testing of serum electrolyte and creatinine concentrations before treatment since the 1990s. We wished to examine the extent of laboratory monitoring in patients with newly diagnosed hypertension and newly treated with antihypertensive drugs.METHODSWe carried out a retrospective analysis of 74 096 patients in the General Practice Research Database (GPRD) aged 18 years and older with newly diagnosed hypertension and prescribed a single antihypertensive agent. We determined the number of patients with a laboratory test for serum electrolyte and creatinine (or urea) concentrations prior to the first antihypertensive drug prescription and in the 6 months after and patient factors associated with subsequent monitoring.RESULTSThirty‐four thousand nine hundred and forty‐seven patients (47%) had at least one biochemical test in the 12 months prior to beginning antihypertensive treatment, and 26 946 (36%) had at least one biochemical monitoring test in the 6 months after beginning antihypertensive treatment. Thirteen thousand five hundred and four (18%) had both baseline and monitoring tests. Baseline tests were normal in 11 671 patients (86%), of whom 10 213 (88%) had normal tests at first monitoring. Monitoring was significantly more likely in patients treated with ACE inhibitors than thiazides (adjusted OR 1.90; 95% CI 1.80, 2.00), older patients (adjusted OR 1.23; 95% CI 1.11, 1.36) [individuals aged 80–89 years compared with <40 years], and patients with diabetes mellitus (adjusted OR 2.03; 95% CI 1.91, 2.16).CONCLUSIONBiochemical testing at baseline and monitoring after starting treatment is often omitted in newly diagnosed hypertensive patients. When both are tested, one in eight normal results becomes abnormal.
Oestrogen‐related receptor alpha inverse agonist XCT‐790 arrests A549 lung cancer cell population growth by inducing mitochondrial reactive oxygen species production
Authors: Wang J. , Wang Y. , Wong C. 
Published: February 2010

AbstractObjective:  Although oestrogen‐related receptor α (ERRα) is primarily thought to regulate energy homeostasis, it also serves as a prognostic marker for cancer. The aim of this study was to investigate any connection between ERRα activity and cell population growth.Materials and methods:  XCT‐790, an ERRa specific inverse agonist, was employed to suppress ERRa activity in human non‐small cell lung cancer cells (NSCLC) A549. Gene expressions were detected using quantitative real‐time PCR and Western blot analysis. Mitochondrial mass, membrane potential and reactive oxygen species (ROS) production were measured by staining with Mitotracker green, JC‐1 and CM‐H2DCFDA dyes respectively. Rate of progression through the tricarboxylic acid (TCA) cycle was analysed by measuring activities of citrate synthase and succinate dehydrogenase. Cell cycle analysis was performed by using flow cytometry.Results:  We found that XCT‐790 treatment reduced mitochondrial mass but enhanced mitochondrial ROS production by increasing rate through the TCA cycle, elevating mitochondrial membrane potential (ΔΨm) and down‐regulating expression of superoxide dismutase. It was further demonstrated that XCT‐790‐induced ROS modulated p53 and Rb signalling pathways and suppressed cell replication.Conclusions:  ERRα affects cell cycle mechanisms through modulating mitochondrial mass and function. Dysregulation of this essential pathway leads to elevation in mitochondrial ROS production, which in turn modulates activities of tumour suppressors, resulting in cell cycle arrest.
γ‐secretase inhibitor induces adipogenesis of adipose‐derived stem cells by regulation of Notch and PPAR‐γ
Authors: Huang Y. , Yang X. , Wu Y. , Jing W. , Cai X. , Tang W. , Liu L. , Liu Y. , Grottkau B. E. , Lin Y. 
Published: February 2010

AbstractObjective:  To determine the inhibitory effect and mechanism of Notch signalling on adipogenesis of mouse adipose‐derived stem cells (mASCs).Materials and methods:  Varied concentrations of N‐[N‐(3,5‐difluorophenacetyl)‐l‐alanyl]‐S‐phenylglycine t‐butylester (DAPT) were added to mASCs 3 days before adipogenic induction with insulin‐containing differentiation medium. The process of adipogenesis and ability of lipid droplet accumulation were analysed using oil red‐O staining. The Notch signalling pathway (Notch‐1, ‐2, ‐3, ‐4, Hes‐1 and Hey‐1) and adipogenesis‐related factors (PPAR‐γ, DLK‐1/Pref‐1 and Acrp) were tested using real‐time PCR, Western blot analysis and immunofluorescence staining assays.Results:  We demonstrated that Notch‐2‐Hes‐1 signalling pathway was inhibited dose‐dependently by DAPT in mASCs. In addition, transcription of PPAR‐γ was promoted by DAPT before adipogenic induction, while inhibitor of adipogenesis DLK‐1/Pref‐1 was further depressed. At early stages of differentiation (2–4 days), adipogenesis in mASCs was advanced and significantly enhanced in 5 and 10 μm DAPT pre‐treated cases. On day 4, in differentiated mASCs cases with DAPT pre‐treatment, we also found promotion of activation of de‐PPAR‐γ and depression of HES‐1, DLK‐1/Pref‐1 mRNA and protein expression.Conclusions:  We conclude that blocking Notch signalling with DAPT enhances adipogenesis of differentiated mASCs at an early stage. It may be due to depression of DLK‐1/Pref‐1 and promotion of de‐PPAR‐γ activation, which work through inhibition of Notch‐2‐Hes‐1 pathway by DAPT.
Feasibility of using cryopreserved lymphoblastoid cells to diagnose some lysosomal storage diseases
Authors: De Mello A. S. , Provin F. , Michelin‐Tireli K. , Camelier M. V. , Coelho J. C. 
Published: February 2010

AbstractObjectives:  The Epstein–Barr virus (EBV) is utilized as a tool in the study of cellular biology because of its capacity to transform B‐lymphocytes. For this reason, EBV is used in conservation of human B‐lymphocytes for long periods for subsequent evaluation of lysosomal hydrolase activity. Lymphoblastoid cell lines have several advantages for use over other cell types, such as prompt availability and possibility to develop, characterize and standardize cell banks, to test effects of promising pharmaceutical reagents. The study below presents biochemical data that demonstrate validity of lymphoblastoid cell lines for diagnosis of GM1‐gangliosidosis, Gaucher, Fabry and Pompe diseases and mucopolysaccharidosis type I.Materials and methods:  Cultures were prepared from peripheral blood, collected from 25 normal subjects and 13 affected individuals. Enzyme activities and immunohistochemistry (IHC) were measured. Activities of enzymes β‐galactosidase, β‐glucosidase, α‐iduronidase, α‐galactosidase and α‐glucosidase were measured before and after cryopreservation for 180 days. Enzymatic activity was measured when transformation was confirmed by IHC.Results:  We observed some significant alterations in enzymatic activity of non‐cultured cells when compared to others that had been cultured for 12 days and kept frozen for 180 days.Conclusions:  However, these alterations did not invalidate use of the technology of transformation of lymphoblastoid cell lines with EBV, to diagnose the diseases mentioned above, in view of the fact that the cultured cells, before and after freezing, demonstrated similar enzymatic activities.
Establishment and biological characterization of fibroblast cell line from the Langshan chicken
Authors: Guan W. , He X. , Li L. , Liang H. , Zhao Q. , Pu Y. , Ma Y.‐H. 
Published: February 2010

AbstractObjective:  We needed to establish an embryonic fibroblast cell line from the Langshan chicken (LSCEF61) to preserve their important genetic resources at the cellular level.Material and methods:  The cell line was established from 9‐day‐old embryos by direct explant culture and cryopreservation techniques. Cell morphology, dynamic proliferation and any contamination present were tested, and the karyotype and levels of isoenzymes of lactic dehydrogenase and malic dehydrogenase were analysed. Four types of fluorescent protein exogenous genes for pEGFP‐C1, pEGFP‐N3, pEYFP‐N1 and pDsRed1‐N1 were transfected into the cells.Results:  Showed that the cells were healthy and were of spindle shaped structure, without change in morphology. Cell growth curves were of typical S‐shape. Assays for microbial contamination were negative. The LSCEF61 line showed no cross‐contamination when assessed by isoenzyme analysis. Chromosome number (2n) = 78 on more than 90% of occasions. The four types of fluorescent protein extro‐genes appeared to be expressed effectively with high transfection efficiency between 15.6% and 38.6%.Conclusion:  The cell line met each of the quality control standards required for the American Type Culture Collection. It had not only preserved the genetic resources of the important Langshan chicken at the cellular level, but also provided valuable material for genomic, post‐genomic and somatic cell cloning research and other applications.
Endothelin receptors blockade blunts hypoxia‐induced increase in PAP in humans
Authors: Pham I. , Wuerzner G. , Richalet J.‐P. , Peyrard S. , Azizi M. 
Published: February 2010

Eur J Clin Invest 2010; 40 (3): 195–202AbstractBackground Activation of the endothelin‐1 (ET‐1) pathway may be involved in hypoxia‐induced pulmonary vasoconstriction, increase in pulmonary pressure and high altitude pulmonary oedema. Thus, we investigated the effect of the ETA/ETB receptor antagonist, bosentan, on pulmonary artery systolic pressure (PASP) in healthy subjects (n = 10).Design We used a double‐blind, placebo‐controlled, randomized, cross‐over design to study the effects of a single oral dose of bosentan (250 mg) on PASP after 90‐min‐exposure to normobaric hypoxia (FiO2 = 0·12). We measured PASP and cardiac output by echocardiography, systolic arterial blood pressure, arterial O2saturation (SaO2), and blood gases at rest and during a sub‐maximal exercise.Results PASP in normoxia at rest was 23·5 ± 2·7 and during exercise 39·8 ± 11·6 mmHg (P < 0·0001). During the placebo period, hypoxia induced a significant decrease in SaO2, PaO2and PCO2and increase in pH. PASP at rest increased significantly: 32·1 ± 3·5 mmHg (P < 0·001 vs. normoxia). Bosentan significantly blunted the hypoxia‐induced increase in PASP: bosentan: 27·0 ± 3·3 mmHg,P = 0·002 vs. placebo at rest, but not during exercise: bosentan 39·8 ± 11·6 vs. placebo 43·0 ± 8·5 mmHg, ns. Bosentan had no effect on the hypoxia‐induced changes in blood gases, or on cardiac output and systolic arterial blood pressure, which were not modified by hypoxia.Conclusion A single oral dose of bosentan blunted an acute hypoxia‐induced increase in PASP in healthy subjects, without altering cardiac output or systemic blood pressure.
From kidney to cardiovascular diseases: NGAL as a biomarker beyond the confines of nephrology
Authors: Bolignano D. , Coppolino G. , Lacquaniti A. , Buemi M. 
Published: February 2010

Eur J Clin Invest 2010; 40 (3): 273–276AbstractNeutrophil gelatinase‐associated lipocalin (NGAL), a small 25 kDa stress‐protein released from injured tubular cells after various damaging stimuli, is already known by nephrologists as one of the most promising biomarkers of incoming Acute Kidney Injury. Moreover, recent studies seem to suggest a potential involvement of this factor also in the genesis and progression of chronic kidney diseases. This brief review explores the new interesting involvement of NGAL in the experimental and clinical field of cardiovascular diseases, such as the pathogenesis and clinical manifestations of atherosclerosis, acute myocardial infarction and heart failure. It does not seem difficult that, in the next future, NGAL may become a new missing link between the kidney and the cardiovascular system.