bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea
Authors: Lavigne F. , Petrof B. J. , Johnson J. R. , Lavigne P. , Binothman N. , Kassissia G.‐O. , Al Samri M. , Giordano C. , Dubé N. , Hercz D. , Benedetti A. , Hamid Q. 
Published: June 2013

SummaryBackgroundThe incidence of sleep‐related breathing disorders is correlated with lower and upper airway inflammatory diseases, such as asthma and allergic rhinitis. We hypothesized that corticosteroids treatment would lead to a greater reduction in disease severity in obstructive sleep apnoea syndrome (OSAS) patients with concomitant allergic rhinitis vs. non‐allergic OSAS patients by reducing the level of inflammation in upper airway tissues.ObjectiveThis study was performed to determine whether treatment with intranasal corticosteroids could reduce upper airway inflammation and improve sleep parameters in obstructive sleep apnoea syndrome patients with or without concomitant allergic rhinitis.MethodsObstructive sleep apnoea syndrome patients with (n = 34) or without (n = 21) documented allergic rhinitis voluntarily enrolled in the study and were assessed at baseline and after corticosteroids treatment for 10–12 weeks. Sleep studies were performed and biopsies were obtained from the inferior turbinate, nasopharynx, and uvula. The apnoea–hypopnoea index, sleep quality, and level of daytime alertness were determined, and immunocytochemistry was used to phenotype tissue inflammation.ResultsStandard sleep indices improved following treatment in the entire cohort of obstructive sleep apnoea syndrome patients, with greater improvement seen in the allergic rhinitis group. Allergic rhinitis patients demonstrated significantly improved O2 saturation and a lower supine apnoea–hypopnoea index score after corticosteroid treatment; similar improvements were not seen in the non‐allergic rhinitis group. Eosinophilia was detected at all three sites in the allergic rhinitis group, but not in the non‐allergic rhinitis group. Following treatment, fewer eosinophils and CD4 lymphocytes were documented at all three biopsy sites in the allergic group; the reduction in inflammation was less apparent in the non‐allergic rhinitis group.ConclusionThis study has provided important molecular and clinical evidence regarding the ability of corticosteroids to reduce upper airway inflammation and improve obstructive sleep apnoea syndrome morbidity patients with concomitant allergic rhinitis.
Characteristics of splenic CD8+ T cell exhaustion in patients with hepatitis C
Authors: Sumida K , Shimoda S , Iwasaka S , Hisamoto S , Kawanaka H , Akahoshi T , Ikegami T , Shirabe K , Shimono N , Maehara Y , Selmi C , Gershwin M E , Akashi K 
Published: June 2013

Summary
There is increasing interest in the role of T cell exhaustion and it is well known that the natural history of chronic hepatitis C virus infection (HCV) is modulated by CD8+ T cell immunobiology. There are many pathways that alter the presence of exhaustive T cells and, in particular, they are functionally impaired by inhibitory receptors, such as programmed death-1 (PD-1) and T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3). We obtained spleen, liver and peripheral blood (before and after splenectomy) lymphoid cells from 25 patients with HCV-related cirrhosis undergoing liver transplantation for end-stage disease or splenectomy for portal hypertension. In all samples we performed an extensive phenotypic study of exhaustion markers [PD-1, Tim-3, interferon (IFN)-γ) and their ligands (PD-L1, PD-L2, galectin-9] in CD8+ T cell subpopulations (both total and HCV-specific) and in antigen-presenting cells (APC; monocytes and dendritic cells). In the spleen, total and HCV-specific CD8+ T cells demonstrated enhanced markers of exhaustion, predominantly in the effector memory subpopulation. Similarly, splenic APC over-expressed inhibitory receptor ligands when compared to peripheral blood. Finally, when peripheral blood CD8+ T cells were compared before and after splenectomy, markers of exhaustion were reduced in splenic CD8+ T cells and APC. Our data in HCV-related cirrhosis suggest that CD8+ T cells in the spleen manifest a significantly higher exhaustion compared to peripheral blood and may thus contribute to the failure to control HCV. Counteracting this process may contribute to inducing an effective immune response to HCV.
Randomized, controlled trial of conjunctival autografting combined with subconjunctival bevacizumab for primary pterygium treatment: 1‐year follow‐up
Authors: Nava‐Castañeda Angel , Olvera‐Morales Osiris , Ramos‐Castellon Cynthia , Garnica‐Hayashi Lilia , Garfias Yonathan 
Published: June 2013

AbstractBackgroundTo investigate the efficacy and safety of subconjunctival bevacizumab application as an adjuvant therapy for primary pterygium.DesignThis study was a clinical randomized trial performed at the Institute of Ophthalmology ‘Conde de Valenciana’.ParticipantsForty‐nine patients with primary pterygium were enrolled in the study.MethodsEach primary pterygium patient was randomized after pterygium excision and a conjunctival autograft to receive either a single 2.5 mg/0.1 mL dose of subconjunctival bevacizumab immediately after surgery (group 1); a double 2.5 mg/0.1 mL injection of subconjunctival bevacizumab, one immediately after surgery and the second 15 days after surgery (group 2); or no injection (group 3).Main Outcome MeasuresAutoconjunctival graft presence or absence of ischaemia, necrosis, infection or detachment; surgical bed appearance; and pterygium recurrence at 1‐year follow‐up period were determined.ResultsForty‐nine eyes of 49 patients were included. Sixteen patients were assigned to group 1, 17 to group 2 and 16 to group 3. Patients from groups 1 and 2 showed conjunctival autograft ischaemia at 24 h postoperative (37.5% and 58.8%, respectively, P > 0.05), which disappeared by the first postoperative month. No significant difference in the main outcome measures was found among single versus double‐dose of subconjunctival bevacizumab injection patients. At the end of the study, pterygium recurrences were observed only in group 3 (P < 0.04).ConclusionsA single 2.5 mg/mL subconjunctival bevacizumab injection in conjunction with primary pterygium surgery accomplishing a conjunctival autograft procedure is safe and well tolerated, and is capable of preventing pterygium recurrences when compared with a control group.
Ocular surface abnormalities related to type 2 diabetes are reversed by the opioid antagonist naltrexone
Authors: Zagon Ian S , Sassani Joseph W , Immonen Jessica A , McLaughlin Patricia J 
Published: June 2013

AbstractBackgroundOcular surface complications of type 2 diabetes are associated with reductions in tear production, increased corneal surface sensitivity, and delayed corneal re‐epithelialization. This study examined the efficacy of topical application of the opioid antagonist naltrexone (NTX) in reversing these diabetic‐related ocular surface complications in mice.MethodsThe genetic db/db mouse model of type 2 diabetes, along with C57Bl/6 wild‐type mice were investigated. Tear production was assessed by phenol red impregnated threads, and ocular surface sensitivity was measured using Von Frey filaments. Centrally located, circular corneal abrasions were created in mice and residual epithelial defects measured by fluorescein photography. Animals in each group received topical applications of drops of 10−5 M NTX in sterile Vigamox (Vigamox, Alcon Laboratories, Fort Worth, Texas, USA) or sterile Vigamox alone, and tear production, corneal sensitivity, and reepithelialization were monitored.ResultsIn comparison to diabetic mice receiving vehicle only, db/db mice treated with one drop of NTX demonstrated a marked reversal in dry eye and ocular surface hypersensitivity within 1 h of one drop of NTX. Reversal of the complications in db/db mice usually lasted for 48–90 h. Corneal epithelial repair in db/db mice was enhanced following a regimen of three drops of NTX daily such that by 72 h, residual wounds were one third the size in db/db mice receiving NTX relative to diabetic mice receiving vehicle. Application of Vigamox alone had no effect. No adverse effects of NTX administration were noted in the cornea.ConclusionsThis is the first report of the efficacy of topical NTX in reversing corneal surface complications in type 2 diabetic mice.
Retinal nerve fibre layer thickness measurements by optical coherence tomography in patients with sleep apnoea syndrome
Authors: Sagiv Oded , Fishelson‐Arev Tagil , Buckman Gila , Mathalone Nurit , Wolfson Julia , Segev Eitan , Peled Ron , Lavi Idit , Geyer Orna 
Published: June 2013

AbstractBackgroundThe study aims to investigate whether retinal nerve fibre layer (RNFL) abnormalities can be detected in patients with obstructive sleep apnoea/hypopnoea syndrome with normally appearing optic disc.DesignThis is an observational case‐control study.ParticipantsOne hundred and eight consecutive patients with moderate or severe obstructive sleep apnoea/hypopnoea syndrome (OSAHS) as determined by overnight polysomnography and normal looking discs and 108 age‐matched healthy controls were included in the study.MethodsAll patients underwent RNFL examinations by optical coherence tomography using fast retinal nerve fibre layer thickness scan.Main Outcome MeasuresThe main outcome measure was RNFL thickness.ResultsMultivariate regression analysis results showed that the RNFL was thinner for a patient with OSAHS than that of a normal control in the average by 4.20 μm (P < 0.003), in the superior quadrant by 4.83 μm (P = 0.028) and in the inferior quadrant by 5.19 μm (P = 0.016). RNFL thickness did not correlate with the severity of the disease.ConclusionsRNFL thinning was detected in normal‐looking discs of patients with advanced OSAHS, but the extent of this thinning did not correlate with the severity of the disease. Longitudinal follow‐up is needed to clarify whether RNFL thinning in OSAHS patients with normal clinically appearing optic nerves will eventually lead to glaucoma.
Evaluation of relationship between preoperative bone density values derived from cone beam computed tomography and implant stability parameters: a clinical study
Authors: Salimov Fariz , Tatli Ufuk , Kürkçü Mehmet , Akoğlan Mücahide , Öztunç Haluk , Kurtoğlu Cem 
Published: June 2013

AbstractObjectivesThe aim of this study was to explore the efficacy of bone density value derived from cone beam computed tomography (CBCT) by evaluating its correlation with implant stability parameters including insertion torque value (ITV) and radiofrequency analysis in relation to different clinical variables including location, gender, age, bone quality, and implant diameter.Material and MethodsA total of 65 implants were placed in 17 patients. The bone densities of implant recipient sites were preoperatively recorded using CBCT. Bone quality was subjectively assessed, which depends on the stiffness of the jawbone according to the Lekholm and Zarb index during drilling procedure. The maximum ITV of each implant was recorded using a digital torque meter during implant placement. Resonance frequency measurements were taken using an Osstell® Mentor immediately after implant placement. Data were analyzed statistically.ResultsThe mean bone density, insertion torque, and implant stability quotient values of all implants were 556 ± 80, 37.4 ± 3.3 Ncm, and 73.8 ± 7.2, respectively. Statistically significant correlations were found between bone density values from CBCT and implant stability parameters in relation to all variables.ConclusionBone density assessment using CBCT is an efficient method and significantly correlated with implant stability parameters and Lekholm and Zarb index. Thus, it is possible to predict initial implant stability and possibility of immediate or early loading using CBCT scans prior to implant placement.
Percutaneous endoscopic gastrostomy for decompression of malignant bowel obstruction
Authors: Kawata Noboru , Kakushima Naomi , Tanaka Masaki , Sawai Hiroaki , Imai Kenichiro , Hagiwara Tomoko , Takao Toshitatsu , Hotta Kinichi , Yamaguchi Yuichiro , Takizawa Kohei , Matsubayashi Hiroyuki , Ono Hiroyuki 
Published: June 2013

BackgroundPrevious reports on percutaneous endoscopic gastrostomy (PEG) for bowel decompression have included a relatively small number of patients and the details of post‐procedural outcomes and complications are lacking. The aim of the present study was to evaluate the outcomes and safety of PEG for bowel decompression in a relatively large number of patients with malignant bowel obstruction.Patients and MethodsOver a 10‐year period, 76 patients with malignant bowel obstruction were referred to the main referral cancer center in Shizuoka prefecture for PEG to obtain decompression. The method for gastrostomy was carried out by the pull‐method, the modified introducer method and the percutaneous endoscopic gastrojejunostomy method. Patient demographics, procedural success, complications, elimination of nasal intubation, and survival were reviewed.ResultsSuccessful placement was achieved in 93% of patients (71/76). Procedure‐related complications occurred in 21% ofpatients (15/71), of which the majority involved stomal leakage (eight patients), and wound infection (six patients). There were no procedure‐related deaths. Among the 55 patients who required nasal intubation before PEG, a trans‐gastrostomy intestinal tube was inserted in 16 patients. The need for further nasal intubation was eliminated in 96% of the patients (53/55). The median survival time was 63 days (range, 8–444 days) after PEG placement.ConclusionsPEG for bowel decompression in patients with malignant obstruction can be carried out with an acceptable risk of minor complications. In combination with a trans‐gastrostomy intestinal tube insertion, the elimination of nasal intubation can be achieved in most patients.
Free iron catalyzes oxidative damage to hematopoietic cells/mesenchymal stem cellsin vitroand suppresses hematopoiesis in iron overload patients
Authors: Lu Wenyi , Zhao Mingfeng , Rajbhandary Sajin , Xie Fang , Chai Xiao , Mu Juan , Meng Juanxia , Liu Yongjun , Jiang Yan , Xu Xinnv , Meng Aimin 
Published: June 2013

AbstractObjectivesTransfusional iron overload is of major concern in hematological disease. Iron‐overload‐related dyserythropoiesis and reactive oxygen species (ROS)‐related damage to hematopoietic stem cell (HSC) function are major setbacks in treatment for such disorders. We therefore aim to investigate the effect of iron overload on hematopoiesis in the patients and explore the role of ROS in iron‐induced oxidative damage in hematopoietic cells and microenvironmentin vitro.Patients and methodsThe hematopoietic colony‐forming capacity and ROS level of bone marrow cells were tested before and after iron chelation therapy.In vitro, we first established an iron overload model of bone marrow mononuclear cells (BMMNC) and umbilical cord‐derived mesenchymal stem cells (UC‐MSC). ROS level, cell cycle, and apoptosis were measured by FACS. Function of cells was individually studied by Colony‐forming cell (CFC) assay and co‐culture system. Finally, ROS‐related signaling pathway was also detected by Western blot.ResultsAfter administering deferoxamine (DFO), reduced blood transfusion, increased neutrophil, increased platelet, and improved pancytopenia were observed in 76.9%, 46.2%, 26.9%, and 15.4% of the patients, respectively. Furthermore, the colony‐forming capacity of BMMNC from iron overload patient was deficient, and ROS level was higher, which were partially recovered following iron chelation therapy.In vitro, exposure of BMMNC to ferric ammonium citrate (FAC) for 24 h decreased the ratio of CD34+cell from 0.91 ± 0.12% to 0.39 ± 0.07%. Excessive iron could also induce apoptosis, arrest cell cycle, and decrease function of BMMNC and UC‐MSC, which was accompanied by increased ROS level and stimulated p38MAPK, p53 signaling pathway. More importantly, N‐acetyl‐L‐cysteine (NAC) or DFO could partially attenuate cell injury and inhibit the signaling pathway induced by excessive iron.ConclusionsOur study shows that iron overload injures the hematopoiesis by damaging hematopoietic cell and hematopoietic microenvironment, which is mediated by ROS‐related signaling proteins.
Detection, pharmacokinetics and cardiac effects following administration of clenbuterol to exercised horses
Authors: Knych H. K. , Mitchell M. M. , Steinmetz S. J. , McKemie D. S. 
Published: June 2013

SummaryReasons for performing studyThe use of clenbuterol in performance horses necessitates the establishment of appropriate withdrawal times.ObjectivesTo describe plasma and urine concentrations of clenbuterol following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds.Study designExperimental.MethodsTwenty‐two horses received an oral dose of 0.8 μg/kg bwt of clenbuterol twice daily for 30 days. A second group of 6 horses received clenbuterol according to the escalating dose protocol on the manufacturer's label. Blood and urine samples were collected prior to, throughout and at various times up to 35 days post administration of the final dose. Drug concentrations were measured using liquid chromatography‐mass spectrometry, and plasma data were analysed using noncompartmental analysis. Behavioural and physiological effects were monitored and heart rate was recorded throughout the course of the study.ResultsClenbuterol plasma concentrations were below the limit of quantification (10 pg/ml) of the assay by Day 4 in all horses receiving the chronic low‐dose regimen and by Day 7 in 5 of 6 horses receiving the escalating dosing protocol. Urine clenbuterol concentrations fell below the limit of quantification of the assay between Days 21 and 28 in all 22 horses in the low‐dose group and in 5 of 6 of the horses in the escalating dose group. Muscle fasciculations, sweating and transient increases in heart rate were noted in a small number of horses following clenbuterol administration, but tolerance to these effects occurred rapidly.Conclusions and potential relevanceEstablishment of appropriate withdrawal times for specific racing jurisdictions depends upon the threshold adopted by that specific jurisdiction. This study extends previous studies describing the pharmacokinetics of clenbuterol and describes plasma and urine concentrations following administration of 2 commonly used dosing regimens to racing fit Thoroughbreds, which will allow jurisdictions to establish withdrawal times in order to prevent inadvertent positive regulatory findings.
Characterization of skin‐resident T cells using a crawl‐out method and flow cytometry
Authors: Poot Jacqueline , Thewissen Mariëlle , Booi Darren , Nieuwhof Chris 
Published: June 2013

AbstractA large fraction of the skin‐homing T‐cell population resides in the skin even under resting, non‐inflammatory conditions. Here, we used a crawl‐out culture method to retrieve T cells from human skin and characterized them using flow cytometric analysis. On average, 48000 viable, non‐proliferating cells were retrieved per biopsy. We found that human skin contains a larger fraction of IL‐17‐, IL‐4‐, IL‐10‐ and IL‐22‐positive T cells as compared with paired blood samples. Our research indicates that it is feasible to use the crawl‐out method in combination with flow cytometry to characterize T‐cell subpopulations in patient‐derived skin biopsies. This method enables further study of the skin immune system and could function as a valuable tool for evaluation of the effects of immunotherapy in skin diseases.
Identification and expression of iron regulators in human synovium: evidence for upregulation in haemophilic arthropathy compared to rheumatoid arthritis, osteoarthritis, and healthy controls
Authors: Nieuwenhuizen L. , Schutgens R. E.G. , van Asbeck B. S. , Wenting M. J. , van Veghel K. , Roosendaal G. , Biesma D. H. , Lafeber F. P.J.G. 
Published: June 2013

SummaryRecurrent joint bleeding is the most common manifestation of severe haemophilia resulting in haemophilic arthropathy (HA). Iron plays a central role in the pathogenesis of the two main features of HA: synovitis and cartilage destruction. The aim of this study was to investigate the synovial presence of the iron regulator proteins ferroportin (FPN), hepcidin, haemoglobin scavenger receptor CD163 (CD163), feline leukaemia virus subgroup C (FLVCR), and heme carrier protein 1 (HCP‐1). A comparison of the expression in HA with rheumatoid arthritis (RA), osteoarthritis (OA), and healthy controls (HC) is made. Synovial expression of iron regulators was investigated by immunohistochemistry in human synovial tissue and in a murine haemophilia model. We demonstrate for the first time the synovial presence of the investigated iron regulator proteins. Expression of the iron regulator proteins FPN, CD163, FLVCR, and HCP‐1 was enhanced in HA in comparison to RA, OA, and HC synovium. In addition, in a murine haemophilia model of acute joint bleeding, synovial expression of FPN, CD163, and HCP‐1 was increased. In both human and murine experiment, synovial expression of hepcidin was not altered. These findings indicate the presence of iron regulator proteins in the synovium, demonstrate an enhanced expression of FPN, CD163, FLVCR, and HCP‐1 in HA, and suggest a synovial adaptation mechanism to maintain synovial iron homeostasis in HA.
Therapeutic effects of the direct renin inhibitor, aliskiren, on non‐alcoholic steatohepatitis in fatty liver Shionogi ob/ob male mice
Authors: Kishina Manabu , Koda Masahiko , Kato Jun , Tokunaga Shiho , Matono Tomomitsu , Sugihara Takaaki , Ueki Masaru , Murawaki Yoshikazu 
Published: June 2013

AimNon‐alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin–angiotensin system (RAS) appears to play important roles in NASH. Direct renin inhibitors (DRI) reduce plasma renin activity (PRA) through interaction with the active site of the enzyme and reduce the formation of angiotensin‐II (AT‐II). Therefore, the DRI aliskiren may further suppress the RAS. This study examined the effects of aliskiren on NASH in fatty liver Shionogi (FLS)‐ob/ob male mice that are the closest animal model of metabolic syndrome‐related NASH in humans.MethodsAliskiren (100 mg/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight FLS‐ob/ob mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups.ResultsAmounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of α‐smooth muscle actin positivity, the numbers of F4/80 positive, 8‐hydroxy‐2‐deoxyguanosine positive cells and immunohistochemical staining of 4‐hydroxynonenal were also significantly decreased in the aliskiren group. Levels of RNA expression for transforming growth factor‐β1, connective tissue growth factor and monocyte chemoattractant protein‐1 were significantly lower in the aliskiren group.ConclusionAliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.