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Effective Agent (effective + agent)
Selected AbstractsEtomidate for Pediatric Sedation Prior to Fracture ReductionACADEMIC EMERGENCY MEDICINE, Issue 1 2001Richard Dickinson MD Abstract. Objective: While etomidate is reported as a procedural sedative in adults, its use in children has not been extensively reported. The authors describe their experience with etomidate for procedural sedation in children with extremity fractures and major joint dislocations. Methods: This was a retrospective descriptive chart review. The setting was a university-based emergency department (ED) that follows national guidelines for procedural sedation. Subjects were children less than 18 years old who received etomidate prior to fracture reduction or major joint dislocations. Standardized data were abstracted from the medical records, including patient demographics, diagnosis, weight, types and doses of sedative and analgesic agents used, number of boluses of etomidate, attempts at reduction, complications encountered, vitals signs before, during, and after the reduction, disposition, and the time from procedure to discharge. Descriptive statistics calculated included means and proportions with 95% confidence intervals. Results: Fifty-three children received etomidate for fracture reduction. Their mean age was 9.7; 41.5% were females. Indications for reduction included forearm fractures (38), ankle fractures (12), upper arm fractures (2), and hip dislocations (1). In most cases (83%) reduction was successful after one attempt only. The mean initial and total doses of etomidate were 0.20 mg/kg (range, 0.1 to 0.4) and 0.24 mg/kg (range, 0.13 to 0.52), respectively. Thirteen patients required a second bolus of etomidate or midazolam. Thirty-four patients (64%) were discharged from the ED after a mean observation of 94 minutes (range, 35 to 255). There were no major adverse events (95% CI = 0% to 5.7%). One patient reported nausea and one required a fluid bolus for hypotension. One patient receiving multiple sedatives and opioid analgesics was admitted for observation due to prolonged sedation. No patient required assisted ventilation or intubation. Conclusions: These results suggest that etomidate is a safe and effective agent for procedural sedation in children requiring fracture and major joint reductions. [source] Pharmacology of the Selective 5-HT1B/1D Agonist FrovatriptanHEADACHE, Issue 2002M.B. Comer BSc Objective.,To determine the pharmacological profile of frovatriptan. Background.,Frovatriptan is a new 5-HT1B/1D agonist developed for the treatment of migraine. Methods.,Pharmacological studies were performed using in vitro and in vivo techniques. Results.,Radioligand-binding studies showed that frovatriptan has a high affinity for 5-HT1B and 5-HT1D receptors, and moderate affinity for 5-HT1A, 5-HT1F, and 5-HT7 receptors. In vitro, frovatriptan acts as a potent full agonist at human cloned 5-HT1B and 5-HT1D receptors, and as a moderately potent full agonist at 5-HT7 receptors. Studies of frovatriptan in isolated human arteries demonstrated a lower threshold for constriction of cerebral than coronary vasculature and a bell-shaped dose-response curve was apparent in the coronary arteries. In anesthetized dogs, frovatriptan administration produced no measurable effect on cardiac function or on blood pressure. Frovatriptan had no effects on coronary blood flow following transient coronary artery occlusion, whereas sumatriptan produced a prolonged and significant decrease in coronary blood flow. Conclusion.,The pharmacology of frovatriptan suggests that it should be an effective agent for the acute treatment of migraine, with a low potential for undesirable peripheral effects. [source] Catalposide, a compound isolated from Catalpa Ovata, attenuates induction of intestinal epithelial proinflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in miceINFLAMMATORY BOWEL DISEASES, Issue 5 2004Sang-Wook Kim MD Abstract Certain irinoid-producing plants have been used as herbal anti-inflammatory remedies. Here we evaluated whether catalposide (CATP), a single compound isolated from irinoid-producing plant Catalpa ovata, has a potential for preventing or ameliorating diseases characterized by mucosal inflammation. Preliminary microarray-based gene expression test revealed that CATP, which alone did not significantly affect expression of any of the >8,000 genes analyzed, attenuated the expression of tumor necrosis factor-, (TNF-,)-induced proinflammatory genes including interleukin-8 (IL-8) in human intestinal epithelial HT-29 cells. Down-regulation of IL-8 mRNA accumulation was also reflected by the decreased IL-8 secretion in CATP-treated HT-29 cells. The signal transduction study revealed that CATP significantly attenuates TNF-,-mediated p38 and extracellular signal-regulated kinase (ERK) phosphorylation. Further, CATP reduced NF-,B-mediated transcriptional activation as well as I,-B, degradation. To establish the in vivo relevance of these findings, we examined whether CATP could affect intestinal inflammation in vivo using the mouse model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. Intrarectal administration of CATP dramatically reduced the weight loss, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, CATP suppressed the expression of TNF-,, interleukin-1,, and intercellular adhesion molecule-1 along with the inhibition of NF-, B p65 translocation into nucleus in TNBS colitis. Collectively, current results demonstrate that CATP may be an effective agent for the treatment of diseases characterized by mucosal inflammation. [source] Preliminary study of ciprofloxacin in active Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 1 2002Dr. George L. Arnold Abstract Based on limited reports of the successful use of antibiotics in the treatment of Crohn's disease (CD) and on the possibility that intestinal bacteria may be one of the etiologic factors playing a role in the pathogenesis of this condition, we undertook a study to evaluate the use of a broad-spectrum antibiotic in CD. Our team studied the efficacy of adding the antibiotic ciprofloxacin to the treatment of moderately active, but resistant cases of CD. Forty-seven adults with moderately active CD were randomly assigned treatment with ciprofloxacin 500 mg twice daily versus placebo twice daily for 6 months. The primary endpoint was the change in scores on the Crohn's Disease Activity Index (CDAI) from baseline to month 6. Although 47 patients were randomized, at 1 month of follow-up 28 patients received ciprofloxacin and 19 received placebo. The mean entry CDAI scores were not significantly different: 187 for the ciprofloxacin group versus 230 for the placebo group (p = 0.638). Mean CDAI scores at the completion of study were 112 for the ciprofloxacin group (n = 25) and 205 for the placebo group (n = 12), (p < 0.001). Disease remission is defined as a decrease in the CDAI score to less than 150 points. Our preliminary study suggests that ciprofloxacin may be an effective agent when added to the treatment of moderately active, resistant CD. [source] A specific inducible nitric oxide inhibitor, ONO-1714 attenuates inflammation-related large bowel carcinogenesis in male ApcMin/+ miceINTERNATIONAL JOURNAL OF CANCER, Issue 3 2007Hiroyuki Kohno Abstract It is generally assumed that inflammation influences carcinogenesis. We previously reported that dextran sodium sulfate (DSS) strongly enhances colon carcinogenesis in the ApcMin/+ mice and the over-expression of inducible nitric oxide synthase (iNOS) contributes to this enhancement. In the current study, we investigated the effect of a selective iNOS inhibitor, ONO-1714 on colitis-related colon carcinogenesis in the ApcMin/+ mouse treated with DSS. Male C57BL/6J ApcMin/+ and Apc+/+ mice were exposed to 1% DSS in their drinking water for 7 days. ONO-1714 was given to the mice at a dose level of 50 or 100 ppm in diet for 5 weeks (during the administration of DSS). The tumor inhibitory effects by ONO-1714 were assessed at week 5 by counting the incidence and multiplicity of colonic neoplasms. Additionally, we assessed serum lipid levels and colonic mRNA expression for cyclooxygenase (COX)-2, iNOS, tumor necrosis factor (TNF)-, and interleukin (IL)-1,. Feeding with ONO-1714 significantly inhibited the occurrence of colonic adenocarcinoma in a dose-dependent manner in the ApcMin/+ mice. In addition, the treatment with ONO-1714 significantly lowered the serum triglyceride levels and mRNA expression levels of COX-2, TNF, and IL-1, of colonic mucosa in the DSS-treated ApcMin/+ mice. Neither ONO-1714 nor DSS affected the colonic pathology in the Apc+/+ mice. Our findings may suggest that ONO-1714 could therefore serve as an effective agent for suppression of colitis-related colon cancer development in the ApcMin/+ mice. © 2007 Wiley-Liss, Inc. [source] Targeted delivery of salicylic acid from acne treatment products into and through skin: role of solution and ingredient properties and relationships to irritationINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 4 2004L. Rhein Salicylic acid (SA) is a beta-hydroxy acid and has multifunctional uses in the treatment of various diseases in skin such as acne, psoriasis, and photoaging. One problem often cited as associated with salicylic acid is that it can be quite irritating at pH 3,4, where it exhibits the highest activity in the treatment of skin diseases. We have identified strategies to control the irritation potential of salicylic acid formulations and have focused on hydroalcoholic solutions used in acne wipes. One strategy is to control the penetration of SA into the skin. Penetration of the drug into various layers of skin, i.e. epidermis, dermis, and receptor fluid, was measured using a modified Franz in vitro diffusion method after various exposure times up to 24 h. A polyurethane polymer (polyolprepolymer-15) was found to be an effective agent in controlling delivery of SA. In a dose-dependent fashion it targeted delivery of more SA to the epidermis as compared to penetration through the skin into the receptor fluid. It also reduced the rapid rate of permeation of a large dose of SA through the skin in the first few hours of exposure. A second strategy that proved successful was incorporation of known mild nonionic surfactants like isoceteth-20. These surfactants cleanse the skin, yet due to their inherent mildness (because of their reduced critical micelle concentration and monomer concentration), keep the barrier intact. Also, they reduce the rate of salicylic acid penetration, presumably through micellar entrapment (either in solution or on the skin surface after the alcohol evaporates). Cumulative irritation studies showed that targeting delivery of SA to the epidermis and reducing the rapid early rate of penetration of large amounts of drug through the skin resulted in a reduced irritation potential. In vivo irritation studies also showed that the surfactant system is the most important factor controlling irritancy. SA delivery is secondary, as formulations with less SA content reduced the rate of delivery to the receptor and yet were some of the most irritating formulations tested, presumably due to the action of the specific anionic surfactant on the barrier. Alcohol content also did not appreciably affect irritation and SA delivery; formulations with considerably low alcohol content but containing anionic versus nonionic surfactant systems exhibited considerably higher irritancy. Thus the surfactant type was again the predominant factor in those studies, although arguably alcohol plays some role (solubilization of SA). Results showed that both polymers and mild surfactants work in concert to provide the optimal formulation benefits of targeted delivery and reduced irritation. Synergistic relationships among hydroalcoholic formulation components will be discussed along with the mechanisms likely involved in controlling delivery of SA to skin. [source] Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trialINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Maryam Akhyani MD Background, Rosacea is a common inflammatory disorder of the skin. Systemic antibiotics currently used in the treatment of rosacea are sometimes associated with uncomfortable side effects. Therefore, a need for an effective agent with few side effects and good patient compliance exists. Azithromycin, a macrolide antibiotic with prolonged mode of action, has recently been found to be an effective alternative in the treatment of inflammatory acne. Methods, For evaluation of the efficacy of azithromycin in the treatment of rosacea, we planned a randomized, open, clinical trial study to compare the efficacy of azithromycin with doxycycline in the treatment of this disease. Sixty-seven patients were randomized to receive either azithromycin 500 mg thrice weekly (on Monday, Wednesday, and Saturday) in the first, 250 mg thrice weekly (on Monday, Wednesday, and Saturday) in the second, and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The other group was given doxycycline 100 mg/day for the three months. Clinical assessment was made at baseline, at the end of first, second, third, and 2 months after treatment. Side affects were recorded. The limitation of this study is that there was no blindness. Results, Statistically significant improvement was obtained with both drugs. Neither drug was shown to be more effective than the other. In the azithromycin group four patients had diarrhea, while epigastric burning was seen in two patients using doxycycline. Conclusion, This study indicates that azithromycin is at least as effective as doxycycline in the treatment of rosacea. [source] Binding of several heavy metal ions by polyaspartyl polymers and their application to some Chinese herbal medicinesJOURNAL OF APPLIED POLYMER SCIENCE, Issue 4 2007Bo Sun Abstract Water-insoluble polyaspartyl polymers were synthesized by using water as medium instead of organic medium. Taking Ca2+ as a reference, the binding of several heavy-metal ions, including Pb2+, Cd2+, Hg2+, Cr3+, Cu2+, and Mn2+, by polyaspartyl polymers was studied. The experimental results revealed that polyaspartate is an excellent binding agent for the investigated heavy-metal ions. These cation ions were bound to polyaspartate polymer by the same mechanism as Pb2+, which can be explained by ion exchange model. Since polyaspartate has a protein-resembling structure that is sensitive to trace heavy metal, it was used to remove some trace heavy-metal elements in Chinese herbal medicines. It was found that polyaspartate material was an effective agent for the removal of Pb2+, Cd2+, and Hg2+ ions from glycyrrhizin, angelica, and gynostemma pentaphyllum. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007 [source] PLC-,2 monitors the drug-induced release of differentiation blockade in tumoral myeloid precursorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Federica Brugnoli Abstract The differentiation therapy in treatment of acute promyelocytic leukemia (APL), based on the administration of all-trans retinoic acid (ATRA), is currently flanked with the use of As2O3, a safe and effective agent for patients showing a resistance to ATRA treatment. A synergy between ATRA and As2O3 was also reported in inducing granulocytic differentiation of APL-derived cells. We have demonstrated that phospholipase C-,2 (PLC-,2), highly expressed in neutrophils and nearly absent in tumoral promyelocytes, largely increases during ATRA treatment of APL-derived cells and strongly correlates with the responsiveness of APL patients to ATRA-based differentiating therapies. Here we report that, in APL-derived cells, low doses of As2O3 induce a slight increase of PLC-,2 together with a moderate maturation, and cooperate with ATRA to provoke a significant increase of PLC-,2 expression. Remarkably, the amounts of PLC-,2 draw a parallel with the differentiation levels reached by both ATRA-responsive and -resistant cells treated with ATRA/As2O3 combinations. PLC-,2 is not necessary for the progression of tumoral promyelocytes along the granulocytic lineage and is unable to overcome the differentiation block or to potentiate the agonist-induced maturation. On the other hand, since its expression closely correlates with the differentiation level reached by APL-derived cells induced to maturate by drugs presently employed in APL therapies, PLC-,2 represents indeed a specific marker to test the ability of differentiation agents to induce the release of the maturation blockade of tumoral myeloid precursors. J. Cell. Biochem. 98: 160,173, 2006. © 2006 Wiley-Liss, Inc. [source] Recent concepts in plaque formationJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2003J.-P. Bernimoulin Abstract Dental plaque is an adherent, bacterial film, and is the main pathological agent for periodontal diseases. The formation of dental plaque can occur both supragingivally and subgingivally. The development of plaque is a three-step process. Following the formation of a pellicle, pioneer micro-organisms will adhere to it, proliferate and form colonies. The final stage involves the aggregation of filamentous organisms and spirochetes into a cohesive biofilm. Many products of the plaque bacteria reach the subepithelial tissue, causing inflammatory responses such as increased vascularity and leukocyte diapedesis. Both supragingival and subgingival plaque may form a hard, mineralized mass called calculus. The surface of calculus harbours bacteria, which may exacerbate the inflammatory responses. An effective oral antiseptic must be active against a wide range of Gram-positive and Gram-negative bacterial species, including streptococci and fusobacteria. Ideally, an effective agent would also penetrate the plaque biofilm. Data show that essential oil and chlorhexidine mouthwashes have the broadest antimicrobial effects. [source] Two-dimensional electrophoresis with cationic detergents, a powerful tool for the proteomic analysis of myelin proteins.JOURNAL OF NEUROSCIENCE RESEARCH, Issue 4 2008Part 1: Technical aspects of electrophoresis Abstract The analysis of proteins in damaged myelin is crucial to clarify the mechanisms of dysmyelination and demyelination. In the present study, proteomic analysis of myelin using a modified two-dimensional electrophoresis (2-DE) method was carried out to obtain a better understanding of myelin biology. Although standard 2-DE (immobilized pH gradient isoelectric focusing/sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IPG/SDS-PAGE) methods of analysis provide high resolutions of soluble proteins with isoelectric focusing points in the pH range of 4,8, major myelin components include highly basic proteins are compacted at the basic edge of the 2-DE gels and are not sufficiently separated for satisfactory analysis. In an attempt to improve the separation of these proteins, an alternative 2-DE method using the cationic detergents was applied. In part 1 of this study, we describe technical aspects of conditioning 2-DE using cationic detergent. In the accompanying paper (part 2), practical 2-DE analysis using cationic detergents is described to identify proteins in the purified CNS myelin fraction. We carried out benzyldimethyl- n -hexadecylammonium chloride (16-BAC)/SDS-PAGE 2-DE and tested 2-DE with four other cationic detergents. We found that 16-BAC was the most effective agent for separation of myelin proteins and that hexadecyltrimethylammonium bromide (cetyltrimethylammonium bromide; CTAB) was the most effective agent for solubilization of myelin proteins. The combination of 16-BAC/SDS-PAGE and CTAB/SDS-PAGE is a powerful tool for the analysis of myelin proteins, including highly basic, high-MW (MW > 100K), and integral membrane proteins. © 2007 Wiley-Liss, Inc. [source] Clinical trial: a dose,response study of fospropofol disodium for moderate sedation during colonoscopyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2008L. B. COHEN Summary Background, An effective agent is needed that provides rapid onset of sedation and quick recovery for patients undergoing colonoscopy. Aim, To assess the efficacy and safety of fospropofol disodium in providing sedation in patients undergoing colonoscopy. Methods, A randomized, double-blind, multicentre trial evaluated 127 adult patients who received fospropofol (2, 5, 6.5 or 8 mg/kg) or midazolam 0.02 mg/kg following pre-treatment with fentanyl. Supplemental doses of study medication were allowed to reach a Modified Observer's Assessment of Alertness/Sedation scale score ,4. Efficacy end points included sedation success, measures of clinical benefit, sedation, and recovery as well as patient- and doctor-rated satisfaction. Results, Fospropofol produced a significant dose-dependent increase in sedation success from 24% (2 mg/kg), 35% (5 mg/kg) and 69% (6.5 mg/kg) to 96% (8 mg/kg; P < 0.001). There were also dose-dependent trends for time to sedation, requirements for alternative sedative medication, supplemental doses of sedative and fentanyl, time to ready for discharge and doctor-rated satisfaction scores. Fospropofol was well tolerated, with most adverse events mild-to-moderate in severity. Conclusion, The 6.5 mg/kg dose of fospropofol provides the ideal balance of efficacy and safety for patients undergoing colonoscopy and has been selected for phase 3 clinical development. [source] The chemopreventive compound curcumin is an efficient inhibitor of Epstein-Barr virus BZLF1 transcription in Raji DR-LUC cells,MOLECULAR CARCINOGENESIS, Issue 3 2002Manfred Hergenhahn Abstract To characterize the effects of inhibitors of Epstein-Barr virus (EBV) reactivation, we established Raji DR-LUC cells as a new test system. These cells contain the firefly luciferase (LUC) gene under the control of an immediate-early gene promoter (duplicated right region [DR]) of EBV on a self-replicating episome. Luciferase induction thus serves as an intrinsic marker indicative for EBV reactivation from latency. The tumor promoter 12- O -tetradecanoylphorbol-13-acetate (TPA) induced the viral key activator BamH fragment Z left frame 1 (BZLF1) protein ("ZEBRA") in this system, as demonstrated by induction of the BZLF1 protein-responsive DR promoter upstream of the luciferase gene. Conversely, both BZLF1 protein and luciferase induction were inhibited effectively by the chemopreventive agent curcumin. Semiquantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) further demonstrated that the EBV inducers TPA, sodium butyrate, and transforming growth factor-, (TGF-,) increased levels of the mRNA of BZLF1 mRNA at 12, 24, and 48 h after treatment in these cells. TPA treatment also induced luciferase mRNA with similar kinetics. Curcumin was found to be highly effective in decreasing TPA-, butyrate-, and TGF-,-induced levels of BZLF1 mRNA, and of TPA-induced luciferase mRNA, indicating that three major pathways of EBV are inhibited by curcumin. Electrophoretic mobility shift assays (EMSA) showed that activator protein 1 (AP-1) binding to a cognate AP-1 sequence was detected at 6 h and could be blocked by curcumin. Protein binding to the complete BZLF1 promoter ZIII site (ZIIIA+ZIIIB) demonstrated several specific complexes that gave weak signals at 6 h and 12 h but strong signals at 24 h, all of which were reduced after application of curcumin. Autostimulation of BZLF1 mRNA induction through binding to the ZIII site at 24 h was confirmed by antibody-induced supershift analysis. The present results confirm our previous finding that curcumin is an effective agent for inhibition of EBV reactivation in Raji DR-CAT cells (carrying DR-dependent chloramphenicol acetyltransferase), and they show for the first time that curcumin inhibits EBV reactivation mainly through inhibition of BZLF1 gene transcription. © 2002 Wiley-Liss, Inc. [source] Progressive Hemifacial Atrophy with Linear SclerodermaPEDIATRIC DERMATOLOGY, Issue 5 2005Emine Dervis M.D. She had a linear white-colored sclerotic plaque on the right submandibular area of skin. Histologic findings of the lesion were consistent with a diagnosis of scleroderma. The relationship between progressive facial hemiatrophy and linear scleroderma are discussed. We think that linear scleroderma of childhood and hemifacial atrophy have considerable clinical overlap and these two syndromes appear to be manifestations of the same or related pathogenic processes. Recently, the beneficial effects of 1.25-dihydroxyvitamin D3 (calcitriol) were reported in adults and in children with linear scleroderma. We assessed the efficacy of oral calcitriol treatment in our patient. Our result indicates that calcitriol may be an effective agent for treating localized scleroderma in children. [source] Risk assessment of thiacloprid and its chemical decontamination on eggplant, Solanum melongena L.PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 2 2009Jayakrishnan Saimandir Abstract BACKGROUND: Thiacloprid [(Z)-3-(6-chloro-3-pyridylmethyl)-1,3-thiazolidin-2-ylidenecyanamide; CalypsoÔ] is a systemic insecticide having persistence in the plant system. It was chosen for the management of the eggplant shoot and fruit borer, Leucinodes orbonalis Guen. Management of this insect pest is difficult because it harbours inside the shoot and fruit portions of eggplant. The persistence of thiacloprid on eggplant has not been studied in India. The Food and Agriculture Organisation (FAO) has proposed its maximum residue limit (MRL) on eggplant as 0.7 mg kg,1, and there is a need to validate this value. Since residues were found to be above this level, five different decontamination agents were tested for the decontamination of thiacloprid from eggplant. RESULTS: The half-life of thiacloprid was 11.1 and 11.6 days from trials in 2 years. Safety factors such as theoretical maximum daily intake (TMDI) and maximum permissible intake (MPI) were used to arrive at a risk assessment to human health from the analytical data obtained from the field trials. Thiacloprid at the doses tested (30 and 60 g AI ha,1) was not effective in managing eggplant fruit borer. A waiting period of 3 days before harvest of the fruits after insecticide application and a processing factor (PF) could not ensure a sufficient margin of safety (MOS). Subjecting the data to a processing factor of 60% could not bring the residues below the proposed MRL. CONCLUSION: Thiacloprid is not found to be an appropriate and effective agent for application to eggplant. Either the proposed MRL needs to be revised or good agricultural practice involving thiacloprid for plant protection in eggplant cultivation is required. Copyright © 2008 Society of Chemical Industry [source] WST11, A Novel Water-soluble Bacteriochlorophyll Derivative; Cellular Uptake, Pharmacokinetics, Biodistribution and Vascular-targeted Photodynamic Activity Using Melanoma Tumors as a Model,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005Ohad Mazor ABSTRACT WST11 is a novel negatively charged water-soluble palladiumbacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t1/2= 1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2= 7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2= 20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates. [source] Changes of psychiatric parameters and their relationships by oral isotretinoin in acne patientsTHE JOURNAL OF DERMATOLOGY, Issue 5 2009Bong Jin HAHM ABSTRACT Oral isotretinoin is a highly effective agent for the treatment of moderate to severe acne, but ever since oral isotretinoin was introduced as a modality for acne, the relationship between oral isotretinoin therapy and psychiatric problems, especially depression, has been controversial. The purposes of this study were to know the acute effects of oral isotretinoin therapy on psychiatric symptoms and to investigate the relationships among them, which have not been reported in the published work. This cohort study included 38 acne patients who started oral isotretinoin therapy. Individual patients were examined before administering oral isotretinoin and 2 and 8 weeks after commencement. Acne severity was graded using the Leeds revised acne grading system. Acute psychiatric effects of oral isotretinoin were assessed using a questionnaire authorized by two psychiatrists. This questionnaire included assessments of acne-related quality of life (Assessment of the Psychological and Social Effects of Acne [APSEA]), depression (Beck's depression inventory [BDI]), anxiety (Beck's anxiety inventory [BAI]) and psychopathology (Symptomchecklist-90-revised [SCL-90-R]). Acne grading and APSEA showed similar change patterns. Both improved after 8 weeks of oral isotretinoin treatment. On the other hand, the severity of depression decreased after 2 weeks of treatment. A significant correlation was found between BDI and APSEA, but no correlation was found between BDI and acne grade. These results indicate that oral isotretinoin therapy alleviates depressive symptoms. Improvements in depression are directly related to acne-related life quality improvements rather than to improvement in acne grade. [source] Protective Effect of Sesamol against 3-Nitropropionic Acid-Induced Cognitive Dysfunction and Altered Glutathione Redox Balance in RatsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Puneet Kumar It is a well-known antioxidant, currently being tried against several neurological disorders. The present study was designed to evaluate the potential of sesamol treatment against 3-nitropropionic acid (3-NP)-induced cognitive impairment and oxidative damage in striatal, cortex and hippocampal regions of the rat. The memory performance was assessed by Morris water maze and elevated plus maze paradigms. The oxidative damage was assessed by estimating the total glutathione, reduced glutathione, oxidized glutathione levels and glutathione redox ratio. Glutathione- S -transferase and lactate dehydrogenase enzymes were also measured in different brain areas. 3-NP significantly impaired memory performance as assessed in Morris water maze and elevated plus maze, which was significantly attenuated by sesamol (5, 10 and 20 mg/kg) pre-treatment. On the other hand, 3-NP significantly induced oxidative stress and depleted total glutathione, reduced glutathione, glutathione- S -transferase, lactate dehydrogenase enzyme levels and redox ratio in the striatum, cortex and hippocampal regions as compared to the vehicle-treated group. Sesamol pre-treatment restored oxidative defence possibly by its free radical scavenging activity as compared to the 3NP-treated group. The present study suggests that sesamol could be used as an effective agent in the management of Huntington's disease. [source] The Protective Effect of Bee Venom against Ethanol-Induced Hepatic Injury via Regulation of the Mitochondria-Related Apoptotic PathwayBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Kyung-Hyun Kim Death of hepatocytes is a characteristic feature of chronic liver disease for various causes. Bee venom (Apis mellifera) has been traditionally used for the treatment of various chronic diseases, such as chronic inflammatory arthritis and chronic liver disease. However, the precise mechanism for bee venom in chronic liver disease is not still cleared. To assess the effects of bee venom in chronic liver disease, we investigated the potential role of the bee venom in the ethanol-induced hepatocyte apoptosis. Bee venom treatment inhibited the apoptotic cell morphology and increased the cell viability in ethanol-induced hepatocyte apoptosis. With ethanol treatment, bee venom-treated hepatocytes increased activity of Bcl-2 and Bcl-xL, reduced activity of Bax, Caspase and PARP. In conclusion, bee venom treatment in ethanol-induced hepatocyte apoptosis occurred through the regulation of Bcl family with subsequent inactivation of the Caspase and PARP. These results suggest that bee venom could be an effective agent to reduce ethanol-induced hepatocyte apoptosis. [source] Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantationCLINICAL TRANSPLANTATION, Issue 4 2010Kyota Fukazawa Fukazawa K, Poliac LC, Pretto EA. Rapid assessment and safe management of severe pulmonary hypertension with milrinone during orthotopic liver transplantation. Clin Transplant 2010: 24: 515,519. © 2009 John Wiley & Sons A/S. Abstract:, The incidence of porto-pulmonary hypertension (PPHN) in patients with end stage liver disease is 8.5%. Evidence indicates that proceeding with orthotopic liver transplantation (OLT) in patients diagnosed with severe PPHN (mean pulmonary artery pressure [mPAP] > 45 mmHg) at the time of OLT surgery is associated with high perioperative mortality. We describe a case of severe PPHN that was diagnosed by right heart catheterization at the time of surgery. We quickly determined the reversibility of PPHN with a bolus of milrinone and proceeded with OLT. Further episodes of pulmonary hypertension were successfully managed with continuous milrinone infusion and transesophageal echocardiography monitoring. Reversibility via vasodilator trial after identification of high pulmonary artery pressures (PAP) may be an important indication of the feasibility of OLT. Milrinone may be useful for the rapid identification of the reversibility of high PAP and may be an effective agent to control abrupt increases in PAP during OLT. [source] Metallic Taste: An Unusual Reaction to Botulinum Toxin ADERMATOLOGIC SURGERY, Issue 5 2003Christian Murray MD BACKGROUND Botulinum neurotoxin formulations are safe and effective agents for the treatment of facial rhytides. OBJECTIVES A patient is described who complained of metallic taste after each treatment with botulinum toxin A (BTX-A). RESULTS The sensation of metallic taste diminished after successive treatments with BTX-A, despite adequate dosing for cosmetic purposes. CONCLUSION Metallic taste is associated with the use of numerous medications; however, the pathogenesis remains unclear. Alteration in zinc metabolism, which may occur with BTX-A administration, has been suggested as a possible mechanism. Although this is the first known report of dysgeusia after BTX-A, physicians and patients may be reassured that the taste alteration was self-limited and was not significantly problematic for the patient in our case. [source] Prediction of cardiovascular risk in people with diabetesDIABETIC MEDICINE, Issue 7 2003P. H. Winocour Abstract People with diabetes are at high risk of cardiovascular morbidity and mortality, especially if they have already developed vascular problems. For patients who are apparently free of vascular complications, risk tables are often used to assess the risk of cardiovascular events in the following years, and to decide on treatment with statins or anti-platelet therapy. These risk prediction tables include estimates of traditional cardiovascular risk factors and are based on populations, some of which only contained a very small number of people with diabetes. Multiple problems can be identified with these tables, and many seriously underestimate cardiovascular risk in people with diabetes. Possible ways of addressing this include using risk estimation tools based solely on diabetic populations, adding in additional traditional variables such as triglycerides or left ventricular hypertrophy, including novel cardiovascular risk factors, or intervening at a lower level of estimated risk in people with diabetes compared with non-diabetic subjects. Alternatively, estimates of individual risk could be abandoned and all people with diabetes could be treated with statins and other effective agents. Diabet. Med. 20, 515,527 (2003) [source] Are lobster fisheries being managed effectively?FISHERIES MANAGEMENT & ECOLOGY, Issue 5 2010Examples from New Zealand, Nova Scotia Abstract, Based on performance, management of the New Zealand and Nova Scotia lobster fisheries can be considered successful, but management can be improved by clearer statements of objectives, more efficient mechanics of governance and quicker response to changes in stocks or fisheries. Principal tactics for lobster fishery management are individual transferable quotas and input controls in New Zealand and Nova Scotia respectively. Decision rules were considered important in both approaches and examples are provided of underperforming fisheries in the absence of decision rules. In Nova Scotia, strong fishers' organisations and fishery scientists were effective agents for change, whereas fisher advisory committees operating by consensus were not. In New Zealand, the quota management system provided strong incentives for fishers to become involved in responsible management, to take longer-term views of their resource and to take major management action on their own. [source] What potential role is there for medication treatment in anorexia nervosa?INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 1 2009Scott J. Crow MD Abstract Objective: To review selected issues regarding the development of drug treatments for anorexia nervosa (AN). Method: The existing pharmacotherapy literature for AN is reviewed, and the theoretical and practical considerations are discussed. Results: A very wide variety of drugs have been examined in AN, generally with negative results. There are a number of potential reasons for this finding, including compliance, nutritional deficits, selection of the wrong targets or the wrong outcome measures, use of monotherapy, lack of animal models, or factors intrinsic to AN. Conclusion: Pharmacotherapy provides little benefit in the treatment of AN at present. Several strategies might lead to the identification of more effective agents, including new measurement strategies, identification of novel pharmacologic targets, and consideration of a clinical trials network. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [source] Management of Bone Loss After Organ Transplantation,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2004Adi Cohen Organ transplant recipients experience rapid bone loss and high fracture rates, particularly during the early post-transplant period. Early rapid bone loss occurs in the setting of uncoupled bone turnover with increased bone resorption and decreased bone formation. Because there are no clinical factors that reliably predict post-transplant bone loss and fractures in the individual patient, all transplant recipients should be considered candidates for early preventive therapy for osteoporosis. Long-term transplant recipients with densitometric osteoporosis and/or fractures should also receive treatment. Although active metabolites of vitamin D and bisphosphonates have both shown efficacy, data from clinical trials suggest that bisphosphonates are the safest and most consistently effective agents for the prevention and treatment of post-transplantation osteoporosis in adults. Kidney transplant recipients represent a special population, and more research is needed to delineate the risks and benefits of treating bone disease in these patients. [source] Study Design in Osteoporosis: A European Perspective,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2003Ja Kanis MD The advent of effective agents for the treatment of osteoporosis has led to the view that placebo-controlled trials to test new agents for efficacy are no longer appropriate. Rather, studies of superiority, equivalence, or non-inferiority have been recommended. Such studies require very large sample sizes, and the burden of osteoporotic fracture in a trial setting is substantially increased. Studies of equivalence cannot be unambiguously interpreted because the variance in effect of active comparator agents is too large in osteoporosis. If fracture studies are required by regulatory agencies, there is still a requirement for placebo-controlled studies, although perhaps of shorter duration than demanded at present. [source] Corticosteroid Osteoporosis: Practical Implications of Recent TrialsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000Philip N. Sambrook Abstract Corticosteroids are widely used and effective agents for control of many inflammatory diseases, but osteoporosis is a common problem associated with their long-term use. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis recently have been published, indicating it is possible to prevent or reverse this bone loss. Ultimately, the aim of treatment is to prevent fractures, especially vertebral fractures that are the most common type of fracture associated with corticosteroid therapy, yet it remains unclear exactly which patients should receive prophylaxis. Understanding the differences between these trials is key to interpreting the results, which have important practical implications for patient management. [source] Polyhydroxylated fullerene derivative C60(OH)24 prevents mitochondrial dysfunction and oxidative damage in an MPP+ -induced cellular model of Parkinson's diseaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 16 2008Xiaoqing Cai Abstract To find effective agents for Parkinson's disease (PD) prevention and therapy, we examined the protective effects of the polyhydroxylated fullerene derivative C60(OH)24 in a 1-methyl-4-phenylpyridinium (MPP+)-induced acute cellular PD model in human neuroblastoma cells and the free radical scavenging effects in this model with an electron spin resonance (ESR) spectrometer. Pretreatment with C60(OH)24 at concentrations greater than 20 ,M showed significant protective effects on MPP+ -induced loss in cell viability, decreases in mitochondrial function (including mitochondrial membrane potential and activities of complex I and II), and increases in the levels of reactive oxygen species and oxidative damage to DNA and proteins. In addition, C60(OH)24 acts as a phase 2 enzyme inducer to protect cells from MPP+ -induced decreases in expression of nuclear factor-E2-related factor 2, expression and activity of ,-glutamyl cysteine ligase and level of glutathione. The ESR study showed that C60(OH)24 is a powerful radical scavenger for superoxide, hydroxyl, and lipid radicals. These data suggest that C60(OH)24 is a mitochondrial protective antioxidant with direct radical scavenging activity and indirect antioxidant inducing activity. © 2008 Wiley-Liss, Inc. [source] Polyporenic acid C induces caspase-8-mediated apoptosis in human lung cancer A549 cellsMOLECULAR CARCINOGENESIS, Issue 6 2009Hui Ling Abstract Lung cancer continues to be the leading cause of cancer-related mortality worldwide. This warrants the search for new and effective agents against lung cancer. We and others have recently shown that lanostane-type triterpenoids isolated from the fungal species Poria cocos (P. cocos) can inhibit cancer growth. However, the mechanisms responsible for the anticancer effects of these triterpenoids remain unclear. In this study, we investigated the effect of polyporenic acid C (PPAC), a lanostane-type triterpenoid from P. cocos, on the growth of A549 nonsmall cell lung cancer cells (NSCLC). The results demonstrate that PPAC significantly reduced cell proliferation via induction of apoptosis as evidenced by sub-G1 analysis, annexin V-FITC staining, and increase in cleavage of procaspase-8, -3, and poly(ADP-ribose)-polymerase (PARP). However, unlike our previously reported lanostane-type triterpenoid, pachymic acid, treatment of cells with PPAC was not accompanied by disruption of mitochondrial membrane potential and increase in cleavage of procaspase-9. Further, PPC-induced apoptosis was inhibited by caspase-8 and pan caspase inhibitors but not by a caspase-9 inhibitor. Taken together, the results suggest that PPAC induces apoptosis through the death receptor-mediated apoptotic pathway where the activation of caspase-8 leads to the direct cleavage of execution caspases without the involvement of the mitochondria. Furthermore, suppressed PI3-kinase/Akt signal pathway and enhanced p53 activation after PPAC treatment suggests this to be an additional mechanism for apoptosis induction. Together, these results encourage further studies of PPAC as a promising candidate for lung cancer therapy. © 2008 Wiley-Liss, Inc. [source] Quality changes of treated fresh-cut tropical fruits in rigid modified atmosphere packaging containersPACKAGING TECHNOLOGY AND SCIENCE, Issue 1 2007Vanee Chonhenchob Abstract There has been increasing demand for various fresh-cut tropical fruits. However, their short shelf-life has limited the market increase of this product. Quality changes (firmness, colour, total soluble solids (TSS), titratable acidity (TA), sensory quality and microbial safety) of fresh-cut mangoes, pineapples, melons and mixes of these fruits were evaluated. Chemical treatments to reduce browning, firmness loss and decay of fresh-cut tropical fruits were investigated. The most effective agents for fresh-cut mangoes, pineapples and melons were 0.1m ascorbic acid, 0.2m ascorbic acid and 0.2m ascorbic acid + 0.2m calcium chloride, respectively. Fresh-cut tropical fruits were packaged in various rigid containers (PET, OPS and OPLA). Gas composition in the package headspace and time to reach steady-state condition varied among fresh-cut packaging systems and affected their quality and shelf-life. The effects of package permeability of O2 and CO2 on quality and shelf-life of the fresh-cut products are discussed. Extended shelf-life was observed in fresh-cut mangoes, pineapples and mixes packaged in PET due to reduced O2 and elevated CO2 atmosphere. A modified atmosphere of 6% O2 and 14% CO2 achieved in PET extended the shelf-life of fresh-cut pineapples from 6 to 13 days. Accumulation of CO2 may impart an off-odour of fresh-cut fruits. The results suggested that the shelf-life of fresh-cut fruits could be extended by using proper rigid containers. Suitable mixes to create optimal equilibrium modified atmosphere had a potential to extend shelf-life of short shelf-life fresh-cut tropical fruits. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||