bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor–β1 in supernatants from stored red blood cells inhibits neutrophil locomotion
Authors: Ghio Massimo , Ottonello Luciano , Contini Paola , Amelotti Massimo , Mazzei Clemente , Indiveri Francesco , Puppo Francesco , Dallegri Franco 
Published: July 2003

AbstractStudies comparing transfusion and nontransfusion patients suggest an increased risk of postoperative infections in transfusion groups. Supernatants of blood components have been shown to affect the function of T lymphocytes and natural killer cells. Here, we found that supernatants from stored red blood cells (RBCs) inhibit human neutrophil migration in response to formyl peptides and stimulate neutrophil locomotion. These effects can be observed with high dilutions of RBC supernatants, such as 1:5 × 106 (vol/vol), able to trigger locomotion as well as desensitization of the cells to alternative chemoattractants. The phenomenon might be mediated by chemoattractants present in the supernatants. As RBC supernatants failed to mobilize intracellular free calcium, the chemoattractants should belong to the group of pure chemoattractants, that is, soluble Fas ligand (sFasL) and transforming growth factor–β1 (TGF-β1), known to act without increasing calcium levels. Recombinant TGF-β1, but not sFasL, was found to reproduce the ability of RBC supernatants to both inhibit neutrophil response to formyl peptides and stimulate neutrophil locomotion. Moreover, TGF-β1–immunodepleted supernatants did not display neutrophil-directed activities. Finally, RBC supernatants from RBCs stored after depletion of leukocytes were incapable of affecting neutrophil function. With neutrophils acting as a first-line antimicrobial defense, the ability, shown here, of high dilutions of RBC supernatants to inhibit neutrophil chemotaxis through TGF-β1 may be a relevant determinant of infections in the postoperative period for transfusion patients. Consistently, the neutrophil chemotactic response to formyl peptide was inhibited by the plasma obtained from 5 transfusion patients.
Reconstitution of the Epstein-Barr virus–specific cytotoxic T-lymphocyte response following T-cell–depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation
Authors: Chakrabarti Suparno , Milligan Donald W. , Pillay Deenan , Mackinnon Stephen , Holder Kathleen , Kaur Narinder , McDonald Dorothy , Fegan Christopher D. , Waldmann Herman , Hale Geoff , Rickinson Alan , Steven Neil 
Published: July 2003

AbstractThe recovery of circulating antigen-specific T-cell immunity to Epstein-Barr virus (EBV) was determined in ELIspot assays following allogeneic myeloablative or nonmyeloablative stem cell transplantation (MST/NST). In 8 of 12 MST patients receiving an alemtuzumab-treated graft, the frequency of the EBV-specific reactivities was similar to or greater than that seen in the healthy controls. A response was detectable in 3 of 6 and 6 of 9 patients by 3 and 6 months, respectively, and in all patients by one year following MST. In contrast, only 1 of 9 (95% confidence interval [CI], 0-2.8) patients made a detectable EBV-specific response by 6 months following NST conditioned with fludarabine, melphalan, and alemtuzumab. Responses were detected in 7 of 10 patients by 1 year after NST. Parallel surveillance demonstrated that other virus infections occurred more frequently and earlier after transplantation in NST patients. The use of alemtuzumab in vivo in the nonmyeloablative conditioning might have resulted in the delay in EBV-specific T-cell recovery and increased virus infections.
Are Older French Patients As Willing As Older American Patients to Undertake Chemotherapy?
Authors: Extermann Martine , Albrand Gilles , Chen Hongbin , Zanetta Sylvie , Schonwetter Ronald , Zulian Gilbert B. , Cantor Alan , Droz Jean-Pierre 
Published: July 2003

Purpose: A view often held in Europe is that older Europeans are less willing than older Americans to undertake chemotherapy. This study assesses whether this view is valid. Patients and Methods: Three-hundred twenty outpatients aged 70 years and older were interviewed via anonymous questionnaires: French patients with and without cancer and American patients with and without cancer. The response rate was 61% (195 of 320 questionnaires). Ages ranged from 70 to 95 years (29% aged 80 years and older). Two scenarios were presented: a strong chemotherapy (platinum/taxane combination–like) and a milder chemotherapy (weekly vinorelbine–like). The options were to refuse chemotherapy or to accept for a threshold chance of cure, of life prolongation, or of symptom relief. Functional status, education, self-rated health, and depression were controlled for. Results: French noncancer patients (34%) were less willing to accept the strong chemotherapy than French cancer patients (77.8%), American noncancer patients (73.8%), and American cancer patients (70.5%) (P < .001 for each pair). This was also true for the moderate chemotherapy (67.9% v 100%, 95.2%, and 88.5%, respectively; P < .001). Age and sex did not correlate with response, but self-rated health, cancer status, and nationality did. Thresholds varied from patient to patient. Conclusion: Whereas older French people without cancer are more reluctant than older Americans to envision chemotherapy, older cancer patients in both countries have the same amenability to treatment. Chemotherapy options should be fully discussed with older cancer patients, given that most are willing to consider them.
Stereospecific reduction of the original anticancer drug oracin in rat extrahepatic tissues
Authors: Szotáková Barbora , Skálová Lenka , Jílek Petr , Buchta Vladimír , Wsól Vladimír 
Published: July 2003

Abstract
The liver is the major site of drug metabolism in the body. However, many drugs undergo metabolism in extrahepatic sites and in the gut wall and lumen. In this study, the distribution and activity of reductases in rat that reduced potential cytostatic oracin to its principal metabolite 11-dihydrooracin (DHO) were investigated. The extension and stereospecificity of oracin reduction to DHO were tested in microsomal and cytosolic fractions from the liver, kidney, heart, lung and wall of small intestine, caecum and large intestine. Intestinal bacterial reduction of oracin was studied as well. The amount of DHO enantiomers was measured by HPLC with Chiralcel OD-R as chiral column. Reductive biotransformation of oracin was mostly stereospecific for (+)-DHO, but the enantiomeric ratio differed significantly among individual tissues and subcellular fractions (from 56% (+)-DHO in heart microsomes to 92% (+)-DHO in liver cytosol). Stereospecificity for (-)-DHO (60%) was observed in bacterial oracin reduction in the lumen of small intestine, caecum and large intestine. Shift of the (+)-DHO/(-)-DHO enantiomeric ratio from 90:10 (in liver subcellular fractions) to 60:40 (in-vivo) clearly demonstrated the importance of the contribution of extrahepatic metabolism to the total biotransformation of oracin to DHO.
Hypochlorite scavenging activity of hydroxycinnamic acids evaluated by a rapid microplate method based on the measurement of chloramines
Authors: Firuzi Omidreza , Giansanti Luisa , Vento Roberta , Seibert Cathrin , Petrucci Rita , Marrosu Giancarlo , Agostino Roberta , Saso Luciano 
Published: July 2003

Abstract
Scavengers of hypochlorite (XOCI) could have beneficial effects in diseases in which this oxidant plays a pathogenic role. It has been reported that ferulic acid and chlorogenic acid, the quinic ester of caffeic acid, are good hypochlorite scavengers, but a systematic evaluation of the naturally occurring hydroxycinnamic acids (HCAs), which these substances belong to, has not been performed yet. Thus, in this work we studied, by two different in-vitro methods, the antioxidant activity of five HCAs: p-coumaric acid, ferulic acid, sinapinic acid, caffeic acid and chlorogenic acid. The methods applied in this study were based on the oxidation of human serum albumin (HSA) by XOCI, a new microplate method based on the measurement of chloramines and a previously described carbonyl assay. Firstly, lysine-derived chloramines, in the presence or absence of the HCAs, were detected using 5-thio-2-nitrobenzoic acid (TNB), measuring the absorbance at 415nm by a microplate reader. To remove excess XOCI, Trolox, a known XOCI scavenger, was added before TNB. Secondly, lysine-derived carbonyls, in the presence or absence of the HCAs, were detected by using 2,4-dinitro-phenylhydrazine. Hydroxycinnamic acids appeared active (caffeic≥sinapinic&gt;chlorogenic≅ferulic&gt;p-coumaric acid) by both methods, suggesting possible pharmacological applications for these compounds, which are present at high concentrations in the plant kingdom.
A new animal model for evaluation of long-term growth rate over one month by rhGH/PLGA microcapsule formulations
Authors: Takada Shigeyuki , Kurokawa Tomofumi , Misaki Masafumi , Taira Keiko , Yamagata Yutaka 
Published: July 2003

Abstract
A new animal model to evaluate the long-term growth rate produced by a sustained-release formulation of recombinant human growth hormone (rhGH) over one month was developed and the usefulness of our microcapsule formulations was demonstrated in this model. Long-term pharmacological effects by subcutaneous injection of microcapsules for sustained release of rhGH were evaluated in hypophysectomized (Hpx) rats treated with immunosuppressive agent along with hormone supplement. Copoly(dl-lactic/glycolic)acid (PLGA) microcapsules for sustained release of rhGH, a two-week sustained-release formulation (rhGH-SR-2W) and a one-month sustained-release formulation (rhGH-SR-1M), were prepared by a solid-in-oil-in-water emulsion solvent evaporation technique. Body-weight gain, body-length gain and serum levels of rat insulin-like growth factor-l (rlGF-l) induced by subcutaneous injection of rhGH-SR were compared with those by daily injections of rhGH solution in Hpx rats for 35 days. Serum IGF-l levels in Hpx rats after the injection of rhGH-SR-2W microcapsules were higher than those after daily injections of rhGH solution. Body-length gain, a new parameter, after single injection of rhGH-SR-1M microcapsules demonstrated the higher growth rate than that after daily injections of rhGH solution for 35 days. Thus, single injection of rhGH-SR microcapsules demonstrated long-term pharmacological effects greater than those by daily injections of rhGH solution in a newly developed model, immunosuppressed Hpx rats.
Controlled release of anti-cocaine catalytic antibody from biodegradable polymer microspheres
Authors: Homayoun P , Mandal T , Landry D , Komiskey H 
Published: July 2003

Abstract
Recent reports have shown that anti-cocaine catalytic monoclonal antibody 15A10 reduces the toxic effect of cocaine by increasing its breakdown to systemically inert products ecgonine methylester and benzoic acid. This study reports the microencapsulation of antibody 15A10 using biodegradable poly (lactic-glycolic) acid (PLGA) by double emulsion technique. Formulation parameters such as protein loading, polymer molecular weight and the presence of zinc carbonate were studied for their effects on in-vitro release of antibody from microspheres. The initial burst release was decreased by the reduction of the protein (as % of total ingredients) in the formulation. Although changing the polymer molecular weight did not cause a reduction in initial burst release, it was effective in improving the release rate. The inclusion of zinc carbonate in microsphere preparation resulted in increase in initial burst release. An in-vivo study in mice revealed the presence of antibody in blood up to ten days following subcutaneous injections. These data demonstrate a potential for a sustained-release formulation of monoclonal antibody 15A10 for treatment of cocaine addiction.
Rofecoxib: an update on physicochemical, pharmaceutical, pharmacodynamic and pharmacokinetic aspects
Authors: Ahuja Naveen , Singh Amarjit , Singh Bhupinder 
Published: July 2003

Abstract
Rofecoxib (MK-966) is a new generation non-steroidal anti-inflammatory agent (NSAID) that exhibits promising anti-inflammatory, analgesic and antipyretic activity. It selectively inhibits cyclooxygenase (COX)-2 isoenzyme in a dose-dependent manner in man. No significant inhibition of COX-1 is observed with rofecoxib up to doses of 1000 mg. The pharmacokinetics of rofecoxib has been found to be complex and variable. Mean oral bioavailability after single dose of rofecoxib (12.5, 25 or 50 mg) is 93% with tmax varying widely between 2 and 9 h. It is highly plasma-protein bound and is metabolized primarily by cytosolic reductases to inactive metabolites. Rofecoxib is eliminated predominantly by hepatic metabolism with a terminal half-life of approximately 17 h during steady state. Various experimental models and clinical studies have demonstrated rofecoxib to be superior, or at least equivalent, in anti-inflammatory, analgesic and antipyretic efficacy to comparator nonselective NSAIDs in osteoarthritis, rheumatoid arthritis and other pain models. Emerging evidence suggests that rofecoxib may also find potential use as supportive therapy in various pathophysiologic conditions like Alzheimer's disease, and in various malignant tumours and polyps, where COX-2 is overly expressed. Rofecoxib is generally well-tolerated. Analysis of data pooled from several trials suggests that rofecoxib is associated with fewer incidences of clinically symptomatic gastrointestinal ulcers and ulcer complications vis-à-vis conventional NSAIDs. However, this gastropreserving effect may be negated by concurrent use of low-dose aspirin for cardiovascular risk reduction. Rofecoxib tends to show similar tolerability for renal and cardiothrombotic events as compared with non-naproxen nonselective NSAIDs. No clinically significant drug interaction has been reported for rofecoxib except with diuretics, where it reverses their salt-wasting effect and thus can be clinically exploited in electrolyte-wasting disorders. There is only modest information about the physicochemical and pharmaceutical aspects of rofecoxib. Being poorly water soluble, its drug delivery has been improved using varied formulation approaches. Although it is stable in solid state, rofecoxib is photosensitive and base-sensitive in solution form with its degradation mechanistics elucidated. Analytical determinations of rofecoxib and its metabolites in biological fluids employing HPLC with varied types of detectors have been reported. Isolated studies have also been published on the chromatographic and spectrophotometric assay of rofecoxib and its degradants in bulk samples and pharmaceutical dosage forms. The current article provides an updated overview on the physicochemical, pharmaceutical, pharmacokinetic and pharmacodynamic vistas of rofecoxib.
Transdermal delivery of paracetamol for paediatric use: effects of vehicle formulations on the percutaneous penetration
Authors: Sintov Amnon C , Krymberk Igor , Gavrilov Vladimir , Gorodischer Rafael 
Published: July 2003

Abstract
Paracetamol is a safe and effective analgesic and antipyretic agent, and is one of the most widely used medications for infants and children. The formulations currently available have been designed for oral and rectal administration. However, they are not practical in young patients with vomiting and diarrhoea, or in those who refuse to take the full dose. An alternative route of administration would be a significant contribution to the paediatric pharmacopoeia. The aim of this study was to develop a new transdermal system for optional therapeutic administration of paracetamol in infants and children. In-vivo studies were carried out in animals using a transdermal system of high-loaded, soluble paracetamol in a hydrogel patch, which was also tested in-vitro for 8 h. Although the beneficial contribution of glyceryl oleate to the transdermal penetration of paracetamol seemed to be significant in-vitro, it was shown to be insufficient in-vivo. To improve the penetration of the drug, 4% PEG-40 stearate and 10% ethanol were incorporated as absorption enhancers into the dermal patches. A few hours after application of the improved patches to rats, plasma drug concentrations were elevated to levels comparable with those obtained after oral and subcutaneous administration of a high dose of paracetamol. Since plasma drug concentrations did not reach a constant steady state (as a peak or plateau) during the short-term animal experiments, longer pharmacokinetic studies in conscious animals are necessary.
Spray-dried carbamazepine-loaded chitosan and HPMC microspheres: preparation and characterisation
Authors: Filipović-Grčić Jelena , Perissutti Beatrice , Moneghini Mariarosa , Voinovich Dario , Martinac Anita , Jalšenjak Ivan 
Published: July 2003

Abstract
In this study, the potential of the spray-drying technique for preparing microspheres able to modify the release profile of carbamazepine was investigated. Low-, medium- and high-molecular-weight chitosan and hydroxypropyl methylcellulose (HPMC) in different drug–polymer ratios were used for the preparation of microspheres. The microspheres, characterized by X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC), were also studied with respect to particle size distribution, drug content and drug release. The results indicated that the entrapment efficiency (EE), as well as carbamazepine release profile, depended on polymeric composition and drug– polymer ratios of the microspheres prepared. The best entrapment efficiencies were obtained when chitosan of low-molecular-weight (CL) or HPMC were used for the microencapsulation. For all types of polymer used, the microspheres with low carbamazepine loading (6.3% w/w) showed better control of drug release than the microspheres with higher drug loadings. The HPMC microspheres showed the slowest carbamazepine release profile with no initial burst effect. Carbamazepine release profiles from ternary systems, carbamazepine–CL–HPMC microspheres, depended mostly on HPMC content and showed similar carbamazepine release profile as CL microspheres when HPMC content was low (9:1 CL–HPMC ratio, w/w). Otherwise, the carbamazepine release from CL–HPMC microspheres was remarkably faster than from either chitosan or HPMC microspheres. The release profile of carbamazepine from the microspheres was highly correlated with the crystalline changes occurring in the matrix.
Adverse Drug Events Involving COX-2 Inhibitors
Authors: Verrico Margaret M , Weber Robert J , McKaveney Teresa P , Ansani Nicole T , Towers Adele L 
Published: July 2003

OBJECTIVE: To describe the types and severity of adverse drug-related events (ADEs) observed in patients receiving cyclooxygenase-2 (COX-2) inhibitors and to increase the awareness of risk factors that predispose patients to ADEs associated with COX-2 inhibitors. METHODS: A review of ADEs reported at the University of Pittsburgh Medical Center Presbyterian Hospital (UPMC-P) revealed significant events related to use of celecoxib or rofecoxib. A query of the internal ADE database was performed to identify ADEs involving COX-2 inhibitors from January 1999 to June 2002. A similar query was performed to identify ADEs involving nonselective nonsteroidal antiinflammatory drugs (NSAIDs) reported during this same time period. Utilization data were also collected. RESULTS: Forty-eight ADEs involving 24 patients receiving COX-2 inhibitors were reported and validated via the UPMC-P ADE review process compared with 38 events in 33 patients receiving nonselective NSAIDs. The types of ADEs reported as related to COX-2 inhibitors were similar to those reported in association with nonselective NSAIDs. Forty-two percent of ADEs (n = 20) involving COX-2 inhibitors and 45% of events (n = 17) involving nonselective NSAIDs were classified as severe. All patients receiving COX-2 inhibitors and 91% of patients receiving nonselective NSAIDs exhibited risk factors that increased their risk to experience an ADE; all but 1 of these patients were receiving outpatient COX-2 inhibitor therapy. CONCLUSIONS: The observed ADEs involving COX-2 inhibitors were similar to those associated with nonselective NSAIDs. Most events may have been preventable, highlighting the need for education regarding the appropriate use of COX-2 inhibitors.
Weight Change after an Atypical Antipsychotic Switch
Authors: Ried L Douglas , Renner Bernard T , Bengtson Michael A , Wilcox Brian M , Wilfred W Acholonu 
Published: July 2003

Background Atypical antipsychotics successfully treat schizophrenia and other conditions, with a lower incidence of extrapyramidal side effects than other agents used in treatment of these disorders. However, some atypical antipsychotics are associated with weight gain. Objective To quantify the impact on weight and identify atypical antipsychotics causing the least amount of weight gain among patients switched from risperidone to olanzapine and olanzapine to risperidone. Methods Patients included in the study (n = 86) were ≥18 years and had received ≥2 prescriptions for risperidone or olanzapine for ≥60 days, switched to the other atypical antipsychotic, and were dispensed ≥2 prescriptions for at least 60 days after the index date. Age, weight, and body mass index (BMI) were retrospectively abstracted from automated databases containing patient-specific prescription and vital sign information. Results At the time of their switch, the average patient age was 53.2 years (range 25–83). The average weight change in patients switched to olanzapine (n = 47) was +2.3 kg (p = 0.01) and the BMI change was +0.8 kg/m2 (p = 0.02). The average percent body weight change was +2.8% and the BMI change was +3.0%. The average weight change after patients switched to risperidone (n = 39) was −0.45 kg (p = 0.69) and BMI change was −0.2 kg/m2 (p = 0.64). The average percentage weight change was −0.4% and BMI change was −0.5%. Conclusions Practitioners' concern regarding weight changes after switching atypical antipsychotics seems warranted and patients should be provided consistent, ongoing weight monitoring. Further investigations should examine whether weight changes associated with atypical antipsychotic treatment further jeopardize this already at-risk population for severe comorbid conditions such as hypertension, coronary artery disease, and type 2 diabetes.
Intravenous Corticosteroids to Reduce Gemtuzumab Ozogamicin Infusion Reactions
Authors: Giles Francis J , Cortes Jorge E , Halliburton Terri A , Mallard Susie J , Estey Elihu H , Waddelow Tracey A , Lim JoAnn T 
Published: July 2003

OBJECTIVE: To assess whether the addition of a brief course of intravenous corticosteroids reduces the incidence of infusion-related adverse events associated with gemtuzumab ozogamicin (GO) administration. METHODS: One hundred forty-three sequential patients received GO-based therapy for refractory myeloid leukemias: 110 patients received the standard regimen of acetaminophen 650 mg orally with diphenhydramine 50 mg intravenously and 33 patients received the same premedications with methylprednisolone sodium succinate 50 mg intravenous piggyback (IVPB) prior to infusion and repeated 1 hour into the infusion. RESULTS: Of 110 patients who received GO with standard premedications alone, 32 (29%) had grade 2 or above infusion-related adverse events. In 33 patients who received these premedications with methylprednisolone 50 mg IVPB prior to infusion and repeated 1 hour into the infusion, only 1 (3%) experienced any infusion-related adverse events (p = 0.0009, 95% CI 0.16 to 0.36). There was no significant difference between the patient cohorts in terms of hepatotoxicity, rate of development of hepatic venoocclusive disease, response rates, or infectious complications. CONCLUSIONS: A brief course of intravenous corticosteroids significantly reduces the incidence of GO infusion–related adverse events.