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Increased Efficacy (increased + efficacy)
Selected AbstractsIncreased Efficacies of an Individual Catalytic Site in Clustered Multivalent Dendritic CatalystsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 14-15 2009Govindasamy Jayamurugan Abstract In the studies reported so far on dendrimer-mediated catalysis, the efficacies of the catalytic units were studied and compared primarily across the generations. In order to identify the efficacy of an individual catalytic unit with respect to the number of such units present within a given generation, a series of catalysts were prepared within a generation. Dendrimers incorporated with phosphine-metal complexes were chosen for the study and as many as 11 catalysts within three generations were synthesized. The CC bond-forming reactions, namely, the Heck and the Suzuki coupling reactions, were then selected to study the catalytic efficiencies of the series of partially and fully phosphine-metal complex functionalized dendrimers. The efficacies of the formation of cinnamate and biphenyl, catalyzed by the dendritic catalysts, were compared. The comparative analyses show that an individual catalytic site is far more effective in its catalytic activity when presented in multiple numbers, i.e., in a multivalent dendritic system, than as a single unit within the same generation, i.e., in a monovalent dendritic system. The study identifies the beneficial effects of the multivalent presentation of the catalytic moieties, both within and across the dendrimer generations. [source] Long-Pulsed Dye Laser Treatment for Facial Telangiectasias and Erythema: Evaluation of a Single Purpuric Pass versus Multiple Subpurpuric PassesDERMATOLOGIC SURGERY, Issue 8 2005Shilesh Iyer MD Background and Objective. Subpurpuric treatments with the pulsed dye laser can be effective for treatment of vascular lesions, although less so than when purpuric fluences are used. Increased efficacy may be achieved by performing multiple passes at the time of treatment. We performed a split-face bilateral paired comparison of multiple low-fluence subpurpuric passes compared with a single high-fluence purpuric pass in the treatment of facial telangiectasias. Materials and Methods. Nine patients were included in the study. One cheek was chosen to be treated with four passes of a nonpurpuric fluence, and the contralateral cheek was treated with a single purpuric pass. Reductions in vessel density, diameter, arborization, and background erythema were evaluated 3 weeks after treatment. Results. We found a 43.4% reduction in surface area covered by telangiectasias on the cheek treated with a single purpuric pass compared with 35.9% on the cheek treated with four subpurpuric passes. The purpuric fluences produced greater reduction in vessel diameter and arborization, whereas the subpurpuric protocol was more effective in reducing background erythema. Purpuric fluences were also noted to produce more significant edema and transient hyperpigmentation in one patient. Conclusion. The multipass subpurpuric approach to treatment with the pulsed dye laser is both cosmetically acceptable and effective, although purpuric treatments may be required to effectively eliminate larger-caliber, more highly networked vessels. [source] Synergistic effect of enterocin AS-48 in combination with outer membrane permeabilizing treatments against Escherichia coli O157:H7JOURNAL OF APPLIED MICROBIOLOGY, Issue 6 2005S. Ananou Abstract Aims:, To determine the effects of outer membrane (OM) permeabilizing agents on the antimicrobial activity of enterocin AS-48 against Escherichia coli O157:H7 CECT 4783 strain in buffer and apple juice. Methods and Results:, We determined the influence of pH, EDTA, sodium tripolyphosphate (STPP) and heat on E. coli O157:H7 CECT 4783 sensitivity to enterocin AS-48 in buffer and in apple juice. Enterocin AS-48 was not active against intact cells of E. coli O157:H7 CECT 4783 at neutral pH. However, cells sublethally injured by OM permeabilizing agents (EDTA, STPP, pH 5, pH 8·6 and heat) became sensitive to AS-48, decreasing the amount of bacteriocin required for inhibition of E. coli O157:H7 CECT 4783. Conclusions:, The results presented indicate that enterocin AS-48 could potentially be applied with a considerably wider range of protective agents, such as OM permeabilizing agents, with increased efficacy in inhibiting E. coli O157:H7. Significance and Impact of the Study:, Results from this study support the potential use of enterocin AS-48 to control E. coli O157:H7 in combination with other hurdles. [source] Associations Between Baseline Risk Factors and Vertebral Fracture Risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Olof Johnell Abstract Different risk factors may influence the effectiveness of osteoporosis therapies. The interaction of 30 baseline risk factors and the effectiveness of raloxifene in the MORE study were assessed. The efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. Introduction: The aim of this analysis was to determine the effect of different risk factors on the effectiveness of raloxifene to reduce vertebral fractures in the Multiple Outcomes of Raloxifene Evaluation (MORE) study using logistic regression models. Materials and Methods: The association was assessed using univariate analyses and a multivariate model between 30 potential risk factors at baseline and the risk of vertebral fractures after 3 years in the placebo group, as well as the interaction of risk factors with raloxifene therapy (at a dose of 60 or 120 mg/day). Results and Conclusions: In the univariate analysis of the placebo group, after adjusting for baseline lumbar spine BMD (LS BMD), short stature (odds ratio [OR] = 1.18), age (OR = 1.38), years since menopause (OR = 1.38), impaired cognitive function, visuospatial capabilities (OR = 1.19), impaired musculoskeletal strength (OR = 1.23), low femoral neck BMD (OR = 1.21), and prior vertebral fracture (OR = 4.95) were significantly associated with the incidence of new vertebral fractures. In the univariate analysis, significant interactions were observed between raloxifene treatment and age (p = 0.04), serum triglycerides (p = 0.03), LS BMD (p = 0.08), and diabetes mellitus (p = 0.04). In the multivariate analysis, the effectiveness of raloxifene was independent of almost all risk factors, with the exception of baseline serum triglyceride level and LS BMD, suggesting an increased efficacy of raloxifene in patients with increased triglyceride levels (p = 0.006) and lower LS BMD values (p = 0.008) at baseline. These data suggest that the efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. [source] Comparison of the binding pockets of two chemically unrelated allosteric antagonists of the mGlu5 receptor and identification of crucial residues involved in the inverse agonism of MPEPJOURNAL OF NEUROCHEMISTRY, Issue 2 2006Pari Malherbe Abstract Fenobam [N- (3-chlorophenyl)- N, -(4,5-dihydro-1-methyl-4-oxo-1H -imidazole-2-yl)urea], a clinically validated non-benzodiazepine anxiolytic, has been shown to be a potent and non-competitive metabotropic glutamate (mGlu)-5 receptor antagonist. In the present study, we have used the site-directed mutagenesis coupled with three-dimensional receptor-based pharmacophore modelling to elucidate the interacting mode of fenobam within the seven-transmembrane domain (7TMD) of mGlu5 receptor and its comparison with that of 2-methyl-6-(phenylethynyl)pyridine (MPEP), the prototype antagonist. The common residues involved in the recognition of MPEP and fenobam include Pro6543.36, Tyr6583.40, Thr7806.44, Trp7846.48, Phe7876.51, Tyr7916.55 and Ala8097.47. The differentiating residues between both modulators' interacting modes are Arg6473.29, Ser6573.39 and Leu7435.47. Our data suggest that these chemically unrelated mGlu5 antagonists act similarly, probing a functionally unique region of the 7TMD. Using [3H]inositol phosphates accumulation assay, we have also identified the critical residues involved in the inverse agonist effect of MPEP. The mutation W7846.48A completely blocked the inverse agonist activity of MPEP; two mutations F7876.51A and Y7916.55A, caused a drastic decrease in the MPEP inverse agonism. Furthermore, these three mutations led to an increased efficacy of quisqualate without having any effect on its potency. The fact that the residues Trp7846.48 and Phe7876.51 are essential equally in antagonism and inverse agonism effects emphasizes again the key role of these residues and the involvement of a common transmembrane network in receptor inactivation by MPEP. [source] Treatment of port wine stains with photodynamic therapy, using pulsed dye laser as a Light Source, Compared With Pulsed dye laser alone: A pilot study,LASERS IN SURGERY AND MEDICINE, Issue 4 2005Alun V. Evans MRCP Abstract Background and Objectives Laser-induced photo thermal damage has been combined with photodynamic therapy (PDT) using a systemic photosensitiser to treat vascular lesions. The efficacy of PDT using systemic 5-aminolaevulinic acid (5-ALA) as the photosensitiser and pulsed dye laser (PDL) as the light source in port wine stains (PWS) is unknown. Study Designs/Materials and Methods We conducted an internally controlled pilot study comparing the efficacy of PDT using PDL as a light source, to PDL alone in the treatment of PWS. Results The PWS improved slightly in all patients but no significant difference was found between the three treatment arms in terms of lesional lightening or incidence and severity of side effects. Conclusions There was no evidence of increased efficacy of PDT using PDL as a light source compared to PDL alone. There was also no significant difference in adverse events. Further studies using different treatment regimens over longer periods of time may be warranted. © 2005 Wiley-Liss, Inc. [source] Cardioversion for Atrial Fibrillation: Treatment Options and AdvancesPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 8 2009JAMES A. REIFFEL M.D. Atrial fibrillation (AF) is associated with significant morbidity and mortality. There are two basic approaches to managing AF: slowing the ventricular rate, while allowing the arrhythmia to continue (the rate-control approach), and restoring and maintaining sinus rhythm (the rhythm-control approach) with antiarrhythmic drugs (AADs) and/or ablation, electrical cardioversion (CV), if needed, or both. Strategy trials comparing rate and rhythm control have found no survival advantage of one approach over the other, but other considerations, such as symptom reduction, often necessitate pursuit of rhythm control. Electrical, or direct current, CV is a widely used and effective method for termination of nonparoxysmal AF, although its success can be affected by patient- and technique-related variables. Pharmacological CV options also exist and are preferable in specific circumstances. Both pharmacological and electrical CV are associated with the risk of proarrhythmia. Many AADs are under development for both CV and maintenance of sinus rhythm. Some are atrioselective, such as vernakalant, and target ion channels in the atria, with little or no effects in the ventricle. Vernakalant, currently under Food and Drug Administration review, appears to offer a safer profile than current CV agents and is likely to expand the role of pharmacological CV. Other new AADs that provide increased efficacy or safety while maintaining normal sinus rhythm may also be better than current drugs; if so, rate-rhythm comparisons will differ from those of previous studies. In conclusion, further trials should clarify the long-term safety profiles of new atrioselective agents and other investigational drugs and define their role in the treatment of AF. [source] Reduced dose of lenograstim is as efficacious as standard dose of filgrastim for peripheral blood stem cell mobilization and transplantation: A randomized study in patients undergoing autologous peripheral stem cell transplantationAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2008Selmin Ataergin In vitro studies have demonstrated a 27% increased efficacy of lenograstim over filgrastim. However, equal doses of 10 ,g/kg/day of filgrastim and lenograstim have been recommended for mobilization of CD34+ cells without associated chemotherapy. In this study, we investigated whether a 25% reduced dose of lenograstim at 7.5 ,g/kg/day is equavalent to 10 ,g/kg/day filgrastim for autologous peripheral blood stem cell (PBSC) mobilization and transplantation. A total of 40 consecutive patients were randomized to either filgrastim (n = 20) or lenograstim (n = 20). The two cohorts were similar in regard to disease, sex, body weight, body surface area, conditioning regimens, previous chemotherapy cycles and radiotherapy. Each growth factor was administered for 4 consecutive days. The first PBSC apheresis was done on the 5th day. In the posttransplant period, the same G-CSF was given at 5 ,g/kg/day until leukocyte engraftment. Successful mobilization was achieved in 95% of patients. Successful mobilization with the first apheresis, was achieved in 10/20 (50%) patients in the filgrastim group versus 9/20 (46%) patients in the lenograstim group. No significant difference was seen in the median number of CD34+cells mobilized, as well as the median number of apheresis, median volume of apheresis, percentage of CD34+ cells, and CD34+ cell number. Leukocyte and platelet engraftments, the number of days requiring G-CSF and parenteral antibiotics, the number of transfusions were similar in both groups in the posttransplant period. Lenograstim 7.5 ,g/kg/day is as efficious as filgrastim 10 ,g/kg/day for autologous PBSC mobilization and transplantation. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source] Sunscreens containing the broad-spectrum UVA absorber, Mexoryl® SX, prevent the cutaneous detrimental effects of UV exposure: a review of clinical study resultsPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2008Anny Fourtanier Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones. Aim: To assess the efficacy of sunscreens containing a broad-spectrum UVA absorber the Mexoryl® SX or ecamsule and to compare formulations with and without it through a large number of clinical studies in human volunteers and patients. Methods: The following assessments were conducted: ,Prevention of excessive pigmentation induced by UV exposure in Caucasian and Asian skins using a method that measures pigmentation protection factors (PPF). ,Efficacy against DNA damage by measurement of pyrimidine dimer formation and p53 protein accumulation. ,Protection of immune system using delayed type hypersensitivity (DTH) reactions to recall antigens, isomerization of urocanic acid (UCA), alteration of Langerhans cells (LC) density, morphology and function. ,Reduction of epidermal and dermal alterations induced by repeated UVA or UV solar simulated radiation (SSR) using histology or immunohistology. ,Prevention of the polymorphous light eruption (PMLE) in patients prone to develop this disease. Results: Mexoryl® SX-containing formulations showed a dose-dependent level of protection against pigmentation. For a same sun protection factor (SPF) the higher the UVA protection was, the higher was the PPF. Pyrimidine dimer formation and p53 accumulation were significantly reduced by formulations with Mexoryl® SX. In the studies looking at the suppression of DTH reactions to recall antigens by the different UV spectra, the LC alterations and the cis UCA formation, Mexoryl® SX formulations always showed a higher protective potency than sunscreen without it even when the protection against erythema was similar (products with same SPF). Mexoryl® SX formulations also prevented or significantly decreased to minimal, ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR exposure. It also reduced the enhancement of collagenase 2 mRNA expression induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was essential for the prevention of this photodermatose. Conclusion: Mexoryl® SX formulated in sunscreens or daily use products have been shown to be an effective UV absorber, leading to an increased efficacy of these products against a large number of biological damage induced by UVA, SSR or sun exposure. [source] Recent developments of glaucoma in childrenACTA OPHTHALMOLOGICA, Issue 2009KK NISCHAL Pediatric glaucoma can be a very challenging area of practice. There have been four areas of advances in the last 5-10 years to help improve the outcomes of treatment. Improved pharmacological agents available have been developed for adult glaucoma some of which have been safely used in children , the exception being brimonidine. A better understanding of the dynamics of aqueous flow and how to harness this have led to a safer filtration methodology with the use of antimetabolites especially Mitomycin C. Tubes or setons have been improved in terms of design with valved tubes eg the Ahmed tube , becoming more popular. Lastly, high frequency ultrasound has led to a better understanding and also better delievery of cyclodiode laser ab externo. Endophotocycloablation has also offered increased efficacy of cyloablation. [source] Infliximab (Remicade?) in uveitis: a reviewACTA OPHTHALMOLOGICA, Issue 2009A ABU EL ASRAR Tumor necrosis factor (TNF)-, has been implicated as an important mediator in autoimmune ocular inflammatory disease pathogenesis as shown by animal studies and its detection in the ocular fluids of patients with uveitis. Blockade of TNF-, has emerged as one of the most promising therapies in autoimmune diseases including uveitis. Currently, there are three TNF-, antagonists: two monoclonal antibodies (infliximab and adalimumab) and a soluble receptor that binds soluble TNF-, (etanercept). Infliximab is a chimeric monoclonal antibody directed against TNF-,. It binds with high affinity to both the soluble and the membrane-bound TNF-, and inhibits a broad range of biologic activities of TNF-,. Binding to membrane TNF-, can mediate programmed cell death. Several studies reported that infliximab therapy was rapidly effective and safe treatment for refractory noninfectious uveitis including childhood uveitis and is indicated as rescue therapy for relapses of ocular inflammation or as maintenance therapy when conventional immunosuppression fails. It also allowed a reduction of corticosteroids and immunosuppressive drugs required to control the disease. However, repeated infusions are required to maintain long-term remission. Moreover, infliximab administration is costly and requires hospital admission. Adalimumab, fully humanized monoclonal anti- TNF-, antibody, was also found to be effective and safe therapy for the management of refractory noninfectious uveitis. Several studies reported that infliximab was more effective than etanercept in the treatment of refractory uveitis. Perhaps infliximab's ability to target membrane-bound TNF-, in addition to the soluble form may contribute to its increased efficacy in comparison with etanercept for uveitis. [source] | |||||||||||||