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Maximal Reduction (maximal + reduction)

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Medical Sciences	72%

Selected Abstracts

Action of Celecoxib on Hepatic Metabolic Changes Induced by the Walker-256 Tumour in Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2007
Alexandra Acco
Celecoxib was administered daily (5,50 mg/kg body weight) beginning at the day in which the tumour cells were inocculated. At day 14, the liver was isolated and perfused in order to measure alanine transformation, glycolysis and arginine transformation. Maximal reduction of tumour growth (75%), accompanied by an almost normal weight gain, was attained with a celecoxib dose of 12.5 mg/kg. Diminution of glucose utilization (glycolysis) and inhibition of gluconeogenesis and ureogenesis from alanine caused by the tumor were totally reversed by celecoxib. Oxygen uptake by the liver was also normalized by the drug. Hepatic arginine transformation, which is normally enhanced in rats bearing the Walker-256 tumour, remained elevated in celecoxib-treated animals. It was concluded that preservation of gluconeogenesis and normalization of hepatic glucose utilization can explain, partly at least, the clinical improvement of cancer patients treated with the drug. The lack of action of celecoxib on arginine hydrolysis might indicate that reduction in polyamine synthesis is not a factor contributing to the diminished tumour growth. [source]

Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension study

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2008
D. Lütjohann
Summary Objective:, To assess the long-term efficacy and safety profile of ezetimibe 10 mg/day in patients with homozygous sitosterolemia. Methods:, This was an extension of a multi-centre, randomised, double-blind, placebo-controlled base study in which patients with homozygous sitosterolemia and plasma sitosterol concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or placebo (n = 7) for 8 weeks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive, 1-year extension studies in which ezetimibe 10 mg/day was administered in an open-label manner. Patients remained on their current treatment regimen (e.g. bile salt-binding resins, statins and low-sterol diet) during the base and extension studies. Patients had to be off ezetimibe therapy for , 4 weeks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 26 weeks in the first and second years respectively. The primary efficacy end-point was mean percentage change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension study. Results:, Treatment with ezetimibe 10 mg/day led to significant mean percentage reductions from baseline in plasma concentrations of sitosterol (,43.9%; p < 0.001), campesterol (,50.8%; p < 0.001), low-density lipoprotein (LDL) sterols (,13.1%; p < 0.050), total sterols (,10.3%; p < 0.050) and apolipoprotein (apo) B (,10.1%; p < 0.050). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol and campesterol occurred within the first 52 weeks of treatment and were sustained for the duration of the study. For LDL sterol, total sterols and apo B, maximal reductions were achieved early (by weeks 4 or 16) and waned slightly through the remainder of the study. Overall ezetimibe 10 mg was well tolerated. Conclusion:, In patients with homozygous sitoserolemia, long-term treatment with ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol concentrations with an overall favourable safety and tolerability profile. [source]

The synthetic cannabinoid WIN55212-2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001
Anna Porcella
Abstract The search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212,2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development. [source]

Incubation phase of acute hepatitis B in man: Dynamic of cellular immune mechanisms

HEPATOLOGY, Issue 5 2000
George J.M. Webster
After hepatitis B virus (HBV) infection, liver injury and viral control have been thought to result from lysis of infected hepatocytes by virus-specific cytotoxic T cells. Patients are usually studied only after developing significant liver injury, and so the viral and immune events during the incubation phase of disease have not been defined. During a single-source outbreak of HBV infection, we identified patients before the onset of symptomatic hepatitis. The dynamics of HBV replication, liver injury, and HBV-specific CD8+ and CD4+ cell responses were investigated from incubation to recovery. Although a rise in alanine transaminase (ALT) levels was present at the time of the initial fall in HBV-DNA levels, maximal reduction in virus level occurred before significant liver injury. Direct ex vivo quantification of HBV-specific CD4+ and CD8+ cells, by using human leukocyte antigen (HLA) class I tetramers and intracellular cytokine staining, showed that adaptive immune mechanisms are present during the incubation phase, at least 4 weeks before symptoms. The results suggest that the pattern of reduction in HBV replication is not directly proportional to tissue injury during acute hepatitis B in humans. Furthermore, because virus-specific immune responses and significant reductions in viral replication are seen during the incubation phase, it is likely that the immune events central to viral control occur before symptomatic disease. [source]

Neodymium-YAG Laser for hemangiomas and vascular malformations , long term results

JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 6 2005
Die Behandlung von Hämangiomen und vaskulären Fehlbildungen mit dem Neodymium-YAG-Laser, Langzeitergebnisse
Hämangiom; Lasertherapie; Nd:YAG-Laser; vaskuläre Malformation Summary Background: Hemangiomas and vascular malformations are the most common vascular lesions of infancy. Different lasers can be used for treatment. Nd:YAG laser photocoagulation is particularly effective because of its deep penetration into tissue. Patients and methods: Thirty-one patients, aged from three months to 18,years, with voluminous hemangiomas and venous malformations were treated with a cw-neodymium:YAG laser. The quartz fibre was used in percutaneous and intralesional technique. Long-term follow-up data were acquired by clinical control or a patient questionnaire for a maximal period of eight years. Twenty patients could be evaluated. Results: In the group with hemangiomas (n,=,15), three cases showed nearly complete remission (> 90 %), ten cases had a partial reduction in size (50,,,90 %), in one case there was stable disease and in one case tumor growth. In the group with venous malformations (n,=,5) two cases showed an excellent response (> 90 %), one case a moderate response (25,,,50 %) and in two cases there was no improvement. Adverse effects included scars (40 %), hyper- and hypopigmentation (23 %), mild atrophy (20 %) and a wrinkled texture (17 %). After maximal reduction in size, 30 % of the patients were not satisfied with the laser treatment outcome and elected surgical excision of the residual lesion. Conclusions: The neodymium:yttrium aluminium garnet (Nd:YAG) laser with percutaneous or intralesional application technique is a valuable tool for selected patients with hemangiomas and venous malformations. Zusammenfassung Hintergrund: Hämangiome und vaskuläre Malformationen sind die häufigsten Gefäßfehlbildungen in der Kindheit. Eine Therapieoption stellt die Laserbehandlung dar. Der Nd:YAG-Laser ist besonders effektiv aufgrund seiner hohen Eindringtiefe ins Gewebe. Patienten und Methodik: Insgesamt wurden 31,Patienten im Alter zwischen drei Monaten und achtzehn Jahren mit voluminösen Hämangiomen und venösen Malformationen mit einem cw-Neodymium:YAG-Laser behandelt. Die Laserfaser wurde in perkutaner und intraläsionaler Technik angewendet. Die Nachbeobachtung über einen Zeitraum von maximal acht Jahren erfolgte mittels klinischer Kontrollen oder einem Patientenfragebogen. Von den insgesamt 31,Patienten konnten 20 ausgewertet werden. Ergebnisse: In der Gruppe der Patienten mit Hämangiomen zeigten drei Patienten eine fast vollständige Rückbildung (> 90 %), zehn Patienten eine partielle Rückbildung (50,,,90 %), in einem Fall zeigte sich ein unveränderter Befund und bei einem Patienten beobachteten wir weiterhin Wachstum. In der Gruppe der Patienten mit venösen Malformationen zeigten zwei Patienten ein exzellentes Ansprechen (> 90 %), ein Patient ein moderates Ansprechen (25,,,50 %) und bei zwei Patienten kam es zu keiner Verbesserung. Nebenwirkungen beinhalteten Narben (40 %), Hyper- und Hypopigmentierungen (23 %), geringe Atrophie (20 %) und eine Hautfältelung. Nach vollständiger Rückbildung waren 30 % der Patienten unzufrieden mit dem Ergebnis und unterzogen sich einer operativen Entfernung der Residuen. Schlußfolgerungen: Der Nd:YAG-Laser mit perkutaner und intraläsionaler Applikationstechnik stellt eine wirksame Methode zur Behandlung ausgewählter Patienten mit Hämangiomen und venösen Malformationen dar. [source]

INACTIVATION OF STAPHYLOCOCCUS AUREUS EXPOSED TO DENSE-PHASE CARBON DIOXIDE IN A BATCH SYSTEM

JOURNAL OF FOOD PROCESS ENGINEERING, Issue 1 2009
HUACHUN HUANG
ABSTRACT The inactivation of Staphylococcus aureus exposed to dense-phase carbon dioxide (DPCD) was investigated, and the kinetics of come-up time (CUT) in pressurization was monitored with come-down time (CDT) and temperature fluctuation in depressurization. CUT was about 2.5, 3.5, 4.0 and 4.0 min; CDT was 3.4, 3.7, 4.5 and 4.5 min; lowest temperature of samples in depressurization was 4, ,1, ,15 and ,22C, corresponding to 10, 20, 30 and 40 MPa at 37C. The inactivation behavior of S. aureus was closely related to the variables of process pressure, holding-pressure time (HPT), process temperature and process cycling. The log reduction of S. aureus at 40 MPa for 30-min HPT was significantly greater (P < 0.05), but the inactivation effect at 10, 20 and 30 MPa was similar. The log reduction of S. aureus at 30 and 40 MPa for 60-min HPT was similar and significantly greater (P < 0.05), while the inactivation effect at 10 and 20 MPa was similar. The inactivation of S. aureus against HPT conformed to a fast,slow biphase kinetics; the two stages were well fitted to a first-order model with higher regression coefficients R2 = 1.000 and 0.9238; their respective D values (decimal reduction time) were 16.52 and 70.42 min. As the process temperature increased, the log reduction of S. aureus increased significantly (P < 0.05); the inactivation kinetics of S. aureus versus process temperature was characterized with a fast inactivation rate from 32 to 45C and a slow inactivation rate from 45 to 55C. As compared to one-process cycling for a total of 60-min HPT, four-process cycling resulted in a significant reduction of S. aureus, and its maximal reduction was near to 5 log cycles, indicating that more process cycling caused more inactivation of S. aureus under identical pressure and temperature with equal HPT. However, the maximal reduction was 0.09 and 0.12 log cycles for two- and four-process cyclings with 0-min HPT, indicating that pressurization and depressurization had a lesser effect on the inactivation of S. aureus, while HPT was significant in DPCD to inactivate S. aureus. PRACTICAL APPLICATIONS Dense-phase carbon dioxide (DPCD) is a novel technology to achieve cold pasteurization and/or sterilization of liquid and solid materials, and is likely to replace or partially substitute currently and widely applied thermal processes. This study showed that DPCD effectively inactivated Staphylococcus aureus inoculated in 7.5% sodium chloride broth, and the inactivation behavior of S. aureus was closely related to the pressure, holding-pressure time, temperature and process cycling. Based on this observation, the technology of DPCD can be applied in the pasteurization of foods such as milk and various fruit juices, especially thermal-sensitive materials. [source]

Endothelium-independent Vasorelaxant Effect of Dioclein, a New Flavonoid Isolated from Dioclea grandiflora, in the Rat Aorta

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 11 2000
F. TRIGUEIRO
We have investigated the endothelium-independent vasorelaxant effect of the new Flavonoid dioclein (5,2,,5,-trihydroxy-6,7-dimethoxyflavanone) in the rat aorta. In endothelium-denuded vessels, dioclein induced a concentration-dependent relaxation of aortic rings precontracted with noradrenaline (IC50 = 3.5 ± 0.89 times 10,4 M and KCl (IC50 = 5.2 ± 1.2 times 10,4 M). In the absence of extracellular calcium, dioclein reduced the contraction induced by noradrenaline (maximal reduction approximately 33%) but not that induced by caffeine. Dioclein also produced a concentration-dependent inhibition of the sustained contractions induced by the phorbol ester 12- O -tetradecanoyl phorbol-13-acetate in normal (IC50 = 4.0 ± 0.2 times 10,4 M) and Ca2+ -free solution (IC50 = 4.0 ± 0.3 times 10,4 M). The results indicate that the endothelium-independent vasorelaxant effect of dioclein may be explained by inhibition of contractions dependent on activation of protein kinase C, voltage-dependent Ca2+ influx and on the release of intracellular Ca2+ stores sensitive to noradrenaline. [source]

Optimization of the ohmic contact processing in InAlN//GaN high electron mobility transistors for lower temperature of annealing

PHYSICA STATUS SOLIDI (C) - CURRENT TOPICS IN SOLID STATE PHYSICS, Issue 1 2010
Karol
Abstract In this article, we optimized the ohmic contact processing in InAlN/GaN high electron mobility transistors for the lower temperature of annealing by recessing of metalliza-tion to approach the 2DEG at the InAlN/GaN interface. The ohmic contacts which were recessed down to 5 nm depth and annealed at 700 °C 2 min. exhibited the contact resistance of 0,39 ,mm while the channel sheet resistance was 210 ,/square. These values are comparative to values of contacts processed at more conventional an-nealing conditions (800 °C, 2 min). Moreover we applied the recessed ohmic contact technology to fabricate Schottky barrier (SB) HEMTs and MOSHEMTs with Al2O3 dielectric film. For MOSHEMTs, we measured the maximal reduction of the gate leakage current by about 6 orders of magnitude if compared with SB HEMTs. The maximal drain current of MOSHEMTs was about 750 mA/mm at VGS = 0 V and the maximal extrinsic transconductance (gme) reached 101 mS/mm. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source]

A randomised controlled study comparing conventional and magnetic guidewires in a two-dimensional branching tortuous phantom simulating angulated coronary vessels

CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 5 2007
DPHIL, Steve Ramcharitar MRCP
Objectives: To directly compare the magnetic navigation system (MNS) guidewires with conventional guidewires in branching tortuous phantoms with operators of varying MNS and percutaneous coronary intervention experience. Background: Vessel tortuosity, angulation, and side branches remain limiting factors in coronary interventions. The MNS addresses these limitations by precisely directing the tip of a magnetised guidewire in vivo aided by two permanent adjustable external magnets. Methods: Crossing and fluoroscopy times of six operators were evaluated in five tortuous Perspex® phantom vessels in three consecutive attempts. Standard guidewire (SG) usage was unrestricted. Two 2nd generation magnetic guidewires (MG) were used. Failure was noted if the cross was unsuccessful within 5 min. Results: The magnetic navigation was vastly superior to SG techniques with increasingly tortuous phantoms. It dramatically decreased both the crossing and fluoroscopy times with maximal reduction from 201.7 ± 111 to 36.4 ± 13 sec, P < 0.001 and 204.7 ± 24 to 47.2 ± 19 sec, P < 0.001, respectively. The MNS had a 98.8% procedural success rate compared to 68% with SG techniques. Moreover it considerably limited the amount of wire usage from 5.5 to 1.3. Operators with prior MG experience performed significantly better than those without, except in the simplest phantom where the difference was nonsignificant (33.8 ± 13 sec vs. 41.7 ± 17 sec, P = 0.2). Conclusion: MNS significantly reduces both the crossing and fluoroscopy times in tortuous coronary phantom models achieving excellent success rates with dramatic reductions in guidewire usage. Operators with prior MNS experience had an advantage over the inexperienced. © 2007 Wiley-Liss, Inc. [source]

Acute decrease of coronary flow after indomethacin delivery in newborn lambs

ACTA PAEDIATRICA, Issue 10 2007
Solweig Harling
Abstract Aim: To document the effects of indomethacin (IND) on coronary flow. Methods: We studied nine premature lambs during the first day of life. The gestational age varied between 132 and 134 days (term 145 days) and weight 3.1,4.7 kg. Coronary flow velocities were recorded with an intracoronary Doppler guide wire in the proximal left anterior descending coronary artery (LAD). Average peak flow velocity was measured before, during and after an intravenous IND injection of 0.2 mg per kilogram of body weight. Results: IND increased systemic blood pressure (p < 0.05) and rate pressure product (RPP; p < 0.05) indicating that IND increased cardiac workload. IND decreased coronary average peak flow velocity in all lambs (p < 0.05). The maximal fall in coronary velocity appeared after 3 min (range 1,7 min) and was regained 10 min (range 4,53 min) after the drug delivery. The maximal reduction of coronary average peak flow velocity was 52% (median 26). The recovery time was directly related to the maximal reduction of the coronary average peak flow velocity (R = 0.91, R2 0.84, p < 0.002). Conclusion: Coronary flow velocity decreased markedly in premature born lambs given a bolus dose of IND. [source]