bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of Capacitation of Canine Spermatozoa during Co‐culture with Heterologous Oviductal Epithelial Cells
Authors: Petrunkina AM , Simon K , Günzel‐Apel A‐R , Töpfer‐Petersen E 
Published: November 2003

ContentsProgress of essential steps of the capacitation is coordinated in the oviductal isthmus, where sperm are stored in close contact with the epithelium. A crucial capacitational event is the phosphorylation of sperm membrane proteins. Regulation of the tyrosine phosphorylation by the oviduct has not been examined in dog sperm yet. The aim of this work was to study the effect of dog sperm binding to porcine oviductal epithelium on capacitation‐induced cellular and molecular changes. Epithelial cells were stripped from the oviducts of post‐puberal sows and cultured for 5–7 days at 39°C and 5% CO2on Biomatrix‐covered Chamber slides. Sperm washed through Percoll was co‐incubated with the oviductal epithelium cell cultures in a bicarbonate Tyrode's medium. During co‐incubation, sperm membrane changes, the state of tyrosine phosphorylation and motility were determined after 3, 30, 90, 180, 240 and 360 min. Significant increases in the percentage of capacitated and dead cells were observed in unbound sperm, while bound sperm remained uncapacitated, live and motile. An increasing tyrosine phosphorylation of tail proteins in bound, unbound and control sperm suspensions and a subsequent phosphorylation of head proteins in unbound and control sperm suspensions were observed. A significant difference regarding head phosphorylation (p < 0.05) was found between sperm bound to oviductal epithelium and unbound sperm. Binding occurred mainly in sperm with non‐ phosphorylated heads, while higher proportions of phosphorylated cells were found in unbound populations. The head phosphorylation progressed significantly during incubation in unbound spermatozoa (p < 0.05); however, it was suppressed in population of sperm attached to oviductal epithelium. Significant correlations between motility parameters related to hyperactivation and tail phosphorylation were found in unbound sperm. These observations support the hypothesis that spermatozoa with non‐phosphorylated heads preferentially attach to epithelial cells. It can be concluded that tyrosine phosphorylation of head membrane proteins and capacitation are delayed in canine spermatozoa being in closed contact with oviductal epithelium.
The effect of decaffeination of coffee on gastro‐oesophageal reflux in patients with reflux disease
Authors: Pehl C. , Pfeiffer A. , Wendl B. , Kaess H. 
Published: November 2003

Background:Patients with reflux disease often complain of heartburn after ingestion of coffee. Induction of gastro‐oesophageal reflux has been demonstrated by pH‐metry following the intake of coffee in healthy volunteers. The reflux was reduced when the coffee had undergone a decaffeination process. The aim of this study was to investigate the effect of decaffeination of coffee on reflux in patients with reflux disease.Methods:Seventeen reflux patients underwent two oesophageal 3‐h pH measurements. The patients received, in a double‐blind study design in a randomized order, 300 mL of either regular or decaffeinated coffee together with a standardized breakfast. The fraction time oesophageal pH < 4 was calculated during the three postprandial hours.Results:For regular coffee the fraction time was calculated to a median of 17.9% with a range of 0.7–56.6%. The fraction time was significantly reduced to 3.1% (0–49.9%) after ingestion of decaffeinated coffee.Conclusion:The amount of gastro‐oesophageal reflux induced by the intake of regular coffee in patients with reflux disease can be reduced by the decaffeination of coffee.
The absorption of low‐dose methotrexate in patients with inflammatory bowel disease
Authors: Moshkowitz M. , Oren R. , Tishler M. , Konikoff F. M. , Graff E. , Brill S. , Yaron M. , Gilat T. 
Published: November 2003

Background:Recent clinical trials have demonstrated that methotrexate may have an important therapeutic role in the treatment of patients with inflammatory bowel disease, who are either refractory or intolerant to traditional medical therapy. The aim of this study was to evaluate the pharmacokinetics of low‐dose oral methotrexate in patients with inflammatory bowel disease.Methods:Methotrexate (12.5 mg) was given orally to nine patients with inflammatory bowel disease: five with Crohn's disease, and four with ulcerative colitis, and to six patients with rheumatoid arthritis who served as a control group. Blood samples were drawn at specific intervals to evaluate methotrexate plasma levels.Results:Methotrexate was rapidly absorbed in all patients. Peak concentrations (Cmax) varied considerably, ranging from 0.25–0.87 μM . The mean Cmax values were similar in all patient groups (0.59 ± 0.12, 0.69 ± 0.16 and 0.54 ± 0.18 μM, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean area under curve in 120 min (AUC0–120) was also similar in all patient groups (32.9 + 11.3, 43.6 + 9.9 and 41.8 + 14.9 ng.min/mL, P not significant) for Crohn's disease, ulcerative colitis and rheumatoid arthritis, respectively. The mean time to reach Cmax, (tmax), varied between patient groups (84, 112 and 95 min, respectively, with a significant difference, P<0.02, between the Crohn's disease and ulcerative colitis groups. A negative correlation was found between methotrexate dosage/kg and Cmax (r=−0.74) only in Crohn's disease patients but not in the other patient groups.Conclusions:Orally administered methotrexate is well absorbed in patients with inflammatory bowel disease including those with severe small bowel disease or resection. If methotrexate is proven to be effective in inflammatory bowel disease, it should be administered orally.
Treating the symptoms of gastro‐oesophageal reflux disease: a double‐blind comparison of omeprazole and cisapride
Authors: Galmiche J.‐P. , Barthelemy P. , Hamelin B. 
Published: November 2003

Background: Few studies have specifically addressed the management of the symptoms of gastro‐oesophageal reflux disease, and there are no comparative data in this respect for acid pump inhibitors and prokinetic agents. Methods: Following endoscopy 424 patients presenting with heartburn as the predominant symptom of gastro‐oesophageal reflux disease were randomized to treatment with omeprazole 20 or 10 mg once daily, or cisapride 10 mg four times daily, in a double‐blind, double‐dummy, parallel group, multicentre study. Symptoms and quality of life were assessed at 4 weeks. Patients still experiencing heartburn continued therapy for a further 4 weeks and the assessments were repeated. Results: At 4 weeks, heartburn was resolved in 65% (95% CI: 57–73%), 56% (48–64%) and 41% (32%–49%) of patients treated, respectively, with omeprazole 20 mg and 10 mg once daily, and cisapride. Both omeprazole doses were significantly more effective than cisapride (P < 0.01). The same order of efficacy was observed regardless of the presence of erosive oesophagitis. Regurgitation and epigastric pain also improved to a greater degree with omeprazole than with cisapride. Quality of life was improved in all treatment groups, and the improvement in the reflux dimension of the Gastrointestinal Symptom Rating Scale (GSRS) score was significantly different between groups (P = 0.002). Conclusions: Omeprazole 20 or 10 mg once daily is significantly more effective than cisapride in the resolution of heartburn, regardless of the presence of erosive oesophagitis, and this is accompanied by an improvement in patient quality of life.
Nicotine tartrate liquid enemas for mildly to moderately active left‐sided ulcerative colitis unresponsive to first‐line therapy: a pilot study
Authors: SANDBORN W. J. , TREMAINE W. J. , LEIGHTON J. A. , LAWSON G. M. , ZINS B. J. , COMPTON R. F. , MAYS D. C. , LIPSKY J. J. , BATTS K. P. , OFFORD K. P. , HURT R. D. , GREEN J. 
Published: November 2003

Background: Ulcerative colitis is predominantly a disease of non‐smokers, and transdermal nicotine is therapeutic but often results in side‐effects. Administration of nicotine as a liquid rectal enema results in less systemic nicotine absorption. Aim: To determine the safety and clinical response of nicotine tartrate liquid enemas for active left‐side ulcerative colitis in a pilot study. Methods: Ten non‐smoking patients with mildly to moderately active left‐sided ulcerative colitis unresponsive to first‐line therapy were treated in an open protocol with nightly nicotine tartrate liquid enemas at a dose of 3 mg nicotine base for 1 week then 6 mg for 3 weeks. Clinical assessments were determined at baseline and 4 weeks by endoscopy, physician assessment and a patient diary of daily symptoms. Peak and trough serum nicotine and trough plasma cotinine were determined by gas chromatography/mass spectrometry and high performance liquid chromatography, respectively. Results: After 4 weeks of treatment, 5/7 patients (71%) showed clinical and sigmoidoscopic improvement (per protocol analysis). The other three patients discontinued therapy within 7 days because of inability to retain the liquid enemas. No patients showed histologic improvement. Six of the patients who completed the 4‐week study had peak and trough serum nicotine concentration determined, only 1 of 6 patients had a detectable peak nicotine concentration (value 2.3 ng/mL), and all six patients had undetectable trough nicotine concentrations. The mean trough plasma cotinine concentration was 13 ± 10 ng/mL. Transient and mild adverse events occurred in 4/10 patients (nausea, lightheadedness, tremor, sleep disturbance). Given the low or undetectable serum nicotine concentrations, these adverse events are not likely to be related to the nicotine enemas. Conclusions: Nicotine tartrate liquid enemas administrated at a dose of 3 mg nicotine base/day for 1 week and then 6 mg/day for 3 weeks are safe and appear to result in clinical improvement in some patients with mildly to moderately active, left‐sided ulcerative colitis unresponsive to first‐line therapy. Placebo‐controlled trials are warranted to confirm these preliminary findings.
Age‐dependent eradication of Helicobacter pylori with dual therapy
Authors: TREIBER G. , AMMON S. , KLOTZ U. 
Published: November 2003

Background: Combined treatment using an acid‐inhibiting drug with antibiotics can cure Helicobacter pylori infection. However, eradication rates are highly variable, especially if a proton pump inhibitor is used with amoxycillin. Therefore it is important to define factors/predictors of the clinical outcome. Methods: In a single‐blind study, 60 H. pylori‐positive patients prospectively matched for diagnosis (erosive gastritis, duodenal and gastric ulcer), age (above and below 50 years) and smoking habits were randomly treated (each group n = 20) for 2 weeks with amoxycillin (1 mg b.d.) and either omeprazole (20 mg b.d.), lansoprazole (30 mg b.d.) or ranitidine (300 mg b.d.). Intragastric pH and plasma levels of the administered drugs were monitored over a dosing interval of 12 h. Results: The overall eradication rates were 45% (intention‐to‐treat, ITT, 27/60) or 47% (per protocol 27/58); they did not differ (ITT) between omeprazole (50%), lansoprazole (40%) and ranitidine (45%). Median pH and time at which intragastric pH was above 4 was slightly lower for ranitidine (4.0 ± 1.7; 51 ± 25%) than for omeprazole (5.4 ± 1.1; 77 ± 25%; P < 0.05) or lansoprazole (4.4 ± 1.6; 68 ± 32%). Plasma concentrations of amoxycillin were comparable in all three treatment groups. Post‐treatment H. pylori status was not dependent on those levels, or the drug‐induced extent or duration of increased intragastric pH. However, H. pylori‐eradicated patients were significantly (P < 0.05) older (56 ± 13 years) than patients still H. pylori‐positive (47 ± 14 years). In addition, in patients older than 50 years (n = 33), eradication was higher (P < 0.01) than in patients (n = 25) below 50 years (65 vs. 24%). Eradication rate was highest (75–83%) in subgroups of patients (>50 years and history of peptic ulcer or smokers). Neither activity/grade of peptic ulcer or erosive gastritis nor initial diagnosis were predictors for clinical outcome. Conclusion: The age of patients must be regarded as a major determinant of H. pylori eradication rate and may represent an important factor contributing to the highly variable clinical results.
Ferrous sulphate interacts with captopril
Authors: Schaefer J. P. , Tam Y. , Hasinoff B. B. , Tawfik S. , Peng Y. , Reimche L. , Campbell N. R. C. 
Published: November 2003

Aims
To determine if iron binds strongly to captopril and reduces captopril absorption.
Methods
A variety of in vitro experiments was conducted to examine iron binding to captopril and a randomized, double‐blind, placebo controlled, cross‐over study design was used to assess the in vivo interaction. Captopril (25 mg) was coingested with either ferrous sulphate (300 mg) or placebo by seven healthy adult volunteers. Subjects were phlebotomized and had blood pressure measured at 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 12 h post ingestion. A 1 week washout period was used.
Results
The coingestion of ferrous sulphate and captopril was associated with a 37% (134 ng ml−1 h, 95% CI 41–228 ng ml−1 h, P=0.03) decrease in area under the curve (AUC) for unconjugated plasma captopril. There were no substantial changes in Cmax (mean difference;–32; 95% CI −124–62 ng ml−1 (P=0.57)) or in tmax (mean difference; 0; 95% CI −18–18 min (P=0.65)) for unconjugated captopril when captopril was ingested with iron. There was a statistically insignificant increase in AUC for total plasma captopril of 43% (1312 ng ml−1 h, 95% CI −827–3451 ng ml−1 h P=0.27) when captopril was ingested with iron. The addition of ferric chloride to captopril resulted in the initial rapid formation of a soluble blue complex which rapidly disappeared to be replaced by a white precipitant. The white precipitate was identified as captopril disulphide dimer. There were no significant differences in systolic and diastolic blood pressures between the treatment and placebo groups.
Conclusions
Co‐administration of ferrous sulphate and iron results in decreased unconjugated captopril levels likely due to a chemical interaction between ferric ion and captopril in the gastrointestinal tract. Care is required when coprescribing captopril and iron salts.
The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload
Authors: Jensen P. D. , Heickendorff L. , Pedersen Bent , Bendix‐Hansen K. , Jensen F. T. , Christensen T. , Boesen A. M. , Ellegaard J. 
Published: November 2003

Long‐term follow‐up data are presented on changes in peripheral blood counts and Hb requirements of 11 patients with myelodysplastic syndromes (MDS) during iron chelation treatment with desferrioxamine for up to 60 months. The erythroid marrow activity was indirectly evaluated by repeated determinations of the serum transferrin receptor concentration. The efficacy of iron chelation was evaluated by repeated quantitative determination of the liver iron concentration by magnetic resonance imaging.Reduction in the Hb requirement (≥50%) was seen in 7/11 (64%) patients. Five patients (46%) became blood transfusion independent. Platelet counts increased in 7/11 (64%) patients and the neutrophil counts in 7/9 (78%) evaluable patients. All patients in whom iron chelation was highly effective showed improvement of erythropoietic output accompanied by an increase in the serum transferrin receptor concentration.It is concluded that reduction in cytopenia in MDS patients may be accomplished by treatment with desferrioxamine, if the iron chelation is efficient and the patients are treated for a sufficiently long period of time. Exactly how treatment with desferrioxamine works remains a challenge for further investigation.
Treatment of acute myelogenous leukaemia in patients aged 50–65: idarubicin is more effective than zorubicin for remission induction and prolonged disease‐free survival can be obtained using a unique consolidation course
Authors: Pignon B. , Witz F. , Desablens B. , Leprise P. Y. , Francois S. , Linassier C. , Berthou C. , Caillot D. , Lioure B. , Cahn J. Y. , Casassus P. , Sadoun A. , Audhuy B. , Guyotat D. , Briere J. , Vilque J. P. , Baranger L. , Polin V. , Berthaud P. , Hurteloup P. , Herve P. , Harousseau J. L. 
Published: November 2003

From December 1987 to June 1992, 251 patients aged 50–65 with de novo acute myelogenous leukaemia (AML) were recruited to a multi‐institutional randomized clinical trial. Induction therapy consisted of Ara‐C (200 mg/m2, continuous infusion, days 1–7) with either zorubicin (ZRB) (200 mg/m2, i.v., days 1–4) or idarubicin (IDR) (8 mg/m2, i.v., days 1–5). Consolidation therapy consisted of a single course of intensive chemotherapy with high‐dose Ara‐C (3 g/m2, 3 h infusion, q 12 h, days 1–4) and m‐Amsa (100 mg/m2/d, i.v., days 5–7).The complete remission (CR) rate was (73%) with Ara‐C/IDR versus (60%) with Ara‐C/ZRB (P = 0.033). In multivariate analysis, factors found to be significant in predicting CR were normal karyotype and treatment with IDR. With a median follow‐up of 73 months, the median disease‐free survival (DFS) duration of all CR patients and the probability of CR at 6 years were 17 months and 29%. In multivariate analysis the only factor associated with an increased DFS duration was a normal karyotype. The median event‐free survival (EFS) duration for all evaluable patients and the median overall survival duration for all eligible patients were respectively 7 and 12 months without any difference between induction arms.The study shows that in patients aged 50–65 idarabicin is more effective than zorubicin for remission induction. However, the type of anthracycline did not influence overall survival duration. Using a unique consolidation course, we observed a prolonged DFS which compares favourably with results obtained with more prolonged consolidation therapy or maintenance treatment.
Rapid genetic screening for haemochromatosis using heteroduplex technology
Authors: Jackson Helen A. , Bowen Derrick J. , Worwood Mark 
Published: November 2003

The recently described association between haemochromatosis and mutations in the HFE or HLA‐‘H’ gene has prompted the need for a simple and rapid genetic test capable of detecting multiple mutations simultaneously. Heteroduplex analysis, a new diagnostic technique, fulfills such criteria and we have investigated the potential for the detection of the Cys282Tyr mutation.100 subjects were genotyped using the heteroduplex approach. The results showed clear distinction between individuals who did not carry the mutation, individuals who were heterozygous for the mutation and homozygous individuals. Heteroduplex results obtained by both silver staining and capillary electrophoresis showed 100% concordance with those obtained by restriction digestion of PCR product.
Phenotypic characterization and analysis of allogeneic T cell responses in ZAP-70 dominant negative transgenic mice
Authors: GLADUE R P , ALLEN M , CUNNINGHAM A , GARDNER J , LAQUERRE A M , CONNELLY P A , SHAW A S , MCNEISH J 
Published: November 2003

SUMMARY
Antigen stimulation of T cells results in a series of biochemical events including the interaction of both SH2 domains of ZAP-70 with phosphorylated ITAMS on the T cell receptor. In order to study the physiological relevance of decreasing native ZAP-70–SH2 interaction in vivo, we generated transgenic mice expressing a T cell-specific, dominant negative form of ZAP-70 consisting of only the tandem SH2 domains (ZAP-NC). Phenotypically, these animals had a comparable distribution of lymphocyte subsets in the thymus and spleen compared with the wild-type (WT) controls. However, examination of peripheral blood revealed a slow but progressive decrease in the number of lymphocytes, particularly CD4+ cells, with age (17% reduction by 3 months, 58% reduction by 6 months). Allogeneic responses were then evaluated in vitro as well as in vivo using a subcutaneous sponge matrix implant. Although spleen cells cultured for 4 days in vitro with alloantigen developed normal functional responses, allogeneic responses generated in vivo within a subcutaneous sponge matrix were impaired. This was characterized by a depression in cytotoxic T lymphocyte (CTL) activity, a 82% reduction in the frequency of helper T cells, and a 78% reduction in the capacity of sponge-infiltrating lymphocytes to produce IL-2 in response to secondary antigen stimulation. These results indicate that although overt lymphocyte development and in vitro function were unremarkable, expression of a truncated ZAP-70 affected the in vivo survival of peripheral lymphocytes and altered the in vivo generation of functional activity to alloantigen.
Inhibition of nitric oxide synthase (NOS) aggravates Staphylococcus aureus septicaemia and septic arthritis
Authors: SAKINIENE E , BREMELL T , TARKOWSKI A 
Published: November 2003

SUMMARY
The aim of this study was to assess the role of NO and its metabolites in bacterial arthritis. The murine model of haematogenously acquired septic arthritis was used. Swiss mice treated with NOS inhibitors (NG-monomethyl-l-arginine or Nω-nitro-l-arginine methyl ester) were injected intravenously with toxic shock syndrome toxin-1 (TSST-1) producing Staphylococcus aureus LS-1. Arthritis was evaluated clinically and histopathologically. Serum cytokine levels, bacterial isolates and intracellular capacity of macrophages to kill bacteria were also analysed. The frequency of arthritis in mice treated with NOS inhibitors was three to four-fold higher than that in non-treated controls (75% versus 20%). The severity of arthritis, expressed as mean arthritic index, was 1·4 and 0·4, respectively. Cartilage and/or bone destruction occurred in 63% of NOS inhibitor-treated mice, but only in 10% of controls. Also, the cumulative septicaemia-induced mortality was clearly higher in mice treated with NOS inhibitors compared with non-treated controls. Intracellular killing capacity of the peritoneal macrophages, treated in vitro with NOS inhibitors, was decreased. Thus, 24 h after bacterial inoculation peritoneal macrophages pretreated with NOS inhibitors killed more than 10 times less bacteria than the control ones (P &lt; 0.01). We conclude that NOS inhibitors aggravate S. aureus arthritis, possibly by inducing impairment of the intracellular killing capacity of macrophages.
Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies
Authors: Audrain M A P , Baranger T A R , Moguilevski N , Martin S J , Devys A , Lockwood C M , Muller J Y , Esnault V L M 
Published: November 2003

Abstract
Myeloperoxidase (MPO) is one of the main antigen targets of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitides. It has been suggested that anti-MPO antibodies may recognize a single epitope on recombinant MPO. If confirmed on native MPO, this might allow specific therapeutic intervention with anti-idiotypic MoAbs to prevent antibody–antigen interaction which is thought to cause activation of neutrophils and vasculitis. We searched for restriction in the epitope recognition profile in 50 patients with anti-MPO autoantibodies, using both native and recombinant MPO. Mouse monoclonals were purified and tested in competition assays. At least four epitopes were identified on native MPO using these monoclonals and only two were conserved on recombinant MPO. We found that human MPO autoantibody response was not restricted to a single epitope on native MPO, as all sera tested did not show the same profile in competitive studies with monoclonals. Furthermure, 30% of human anti-native MPO sera failed to recognize rMPO.