Home About us Contact
|
Home About us Contact | ||
|
|
||
Combination Treatment (combination + treatment)
Selected AbstractsHIGH PRESSURE INACTIVATION OF PECTIN METHYL ESTERASE IN ORANGE JUICE USING COMBINATION TREATMENTSJOURNAL OF FOOD BIOCHEMISTRY, Issue 6 2001S. BASAK ABSTRACT The contribution of several high pressure (HP) processing related factors (pressure level, 300-400 MPa; pressure cycle, 1-3, and pressure-hold time, 30,120 min) on the inactivation of pectin methyl esterase (PME) in single strength (pH 3.7 and 11.4 °Brix) and concentrated (pH 3.5 and 42 °Brix) orange juice was evaluated. A response surface methodology was employed to model the combined effects of factors on the enzyme inactivation. The main effects were described by linear or quadratic functions. For both single strength and concentrated orange juices, the effects of all three main factors and some interactions (pressure level, cycle and holding time) were statistically significant (p<0.05). The dual nature of pressure inactivation of PME (with an instantaneous inactivation due to a pressure pulse, instantaneous pressure fall, and first order rate of inactivation during the pressure hold, yielding D and z values) reported in earlier studies was confirmed. Combination models were developed to predict the residual enzyme activity as influenced by the pressure level, number of pressure cycles and pressure hold time. [source] Combination treatment for type 2 diabetesPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2004AN Dixon. No abstract is available for this article. [source] Combination treatment of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitusPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 8 2004AN Dixon MRCP (UK) Clinical Research FellowArticle first published online: 7 DEC 200 Abstract The recently published guidelines from the National Institute for Clinical Excellence (NICE) on the management of blood glucose in type 2 diabetes and the NICE guidelines on the use of the long-acting insulin analogue, glargine, have brought to the fore the use of combination therapy of insulin with oral hypoglycaemic agents (OHAs). The NICE guidelines recommend that when a patient with type 2 diabetes is failing to achieve satisfactory glycaemic control with OHAs alone, insulin should be initiated in combination with OHAs. However, evidence for this approach is less than robust and combination treatment of OHAs with insulin remains a controversial area. This article presents the evidence for different insulin regimens in patients who have secondary failure to OHAs, including combination therapy with basal insulin. The evidence and potential drawbacks of such regimens are discussed. Copyright © 2004 John Wiley & Sons, Ltd. [source] In vivo imaging of retinoic acid receptor ,2 transcriptional activation by the histone deacetylase inhibitor MS-275 in retinoid-resistant prostate cancer cellsTHE PROSTATE, Issue 1 2005David Z. Qian Abstract BACKGROUND In retinoid resistant epithelial tumors, the lack of retinoic acid receptor ,2 (RAR,2) expression due to epigenetic silencing impairs the activation of retinoid target genes including RAR,2, and has been associated with the development of cancer. In this study we developed a strategy to monitor the re-activation of RAR,2 by chromatin remodeling agents combined with retinoids in real time, and to correlate the RAR,2 re-activation with anti-tumor activity. METHODS We selected the RAR,2-negative retinoid resistant human prostate carcinoma cell line PC3 and stably transfected it with a luciferase expression vector under the control of a functional segment of RAR,2 promoter (pGL2-RAR,2-PC3). Then, we used the bioluminescence technology to monitor the reporter gene expression in real time both in vitro and in vivo following combination treatment with the histone deacetylase inhibitor MS-275 and 13- cis retinoic acid (CRA). Based on the effective dose for the RAR,2 re-activation, we tested the anti-tumor activity of this drug combination. RESULTS Following combination treatment with MS-275 and CRA, we observed endogenous RAR,2 re-expression, acetylation at the RAR,2 promoter level, and synergistic activation of the luciferase reporter gene by real time imaging both in vitro and in vivo. Combination treatment with MS-275 and CRA restored retinoid sensitivity in human prostate carcinoma cell lines, and had a greater inhibitory effect on tumor cell growth than single agents in vitro and in vivo. CONCLUSIONS This study provides evidence that HDAC inhibitors restore retinoid sensitivity in prostate cancer cells, and in vivo real time imaging of RAR,2 activation may represent a useful tool to study the pharmacodynamics of combination therapy with HDAC inhibitors and retinoids. © 2005 Wiley-Liss, Inc. [source] Modulation of tamoxifen sensitivity by antisense Bcl-2 and trastuzumab in breast carcinoma cellsCANCER, Issue 10 2005Ph.D., Ryungsa Kim M.D. Abstract BACKGROUND Because the overexpression of HER-2 and Bcl-2 is associated with resistance to tamoxifen (TAM), the authors examined the effect of antisense (AS) Bcl-2 on sensitivity to TAM compared with the effect of trastuzumab on sensitivity to TAM in breast carcinoma cell lines. METHODS Drug sensitivity was assessed in vitro using a [3-4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay with the breast carcinoma cell lines ZR-75-1, MDA-MB-453, and BT-474. AS Bcl-2 18-mer phosphorothioate oligonucleotide was applied. Apoptotic cell death was assessed with the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end labeling method, and gene expression was evaluated with Western blot analysis. RESULTS The expression of Bcl-2 was identified in ZR-75-1 and BT-474 cells and, to a lesser extent, in MDA-MB-453 cells. Overexpression of HER-2 was identified in BT-474 cells, and moderate expression was identified in MDA-MB-453 and ZR-75-1 cells. Combination treatment with trastuzumab or AS Bcl-2 enhanced TAM sensitivity in ZR-75-1 cells, which showed 50% inhibitory concentration (IC50) values of 0.9 ,M (7.2-fold increase) and 0.5 ,M (13.0-fold), respectively. Combination treatment with trastuzumab or AS Bcl-2 slightly enhanced TAM sensitivity of BT-474 cells, with IC50 values of 3.0 ,M (1.3-fold) and 1.5 ,M (2.6-fold), respectively. The sensitivity of MDA-MB-453 cells to TAM was not enhanced by combination with trastuzumab or AS Bcl-2. Modulation of TAM sensitivity by AS Bcl-2 was superior to modulation by trastuzumab in HER-2-expressing and Bcl-2 -expressing breast carcinoma cells. Enhanced sensitivity in combination with AS Bcl-2 was associated with down-regulation of Bcl-2 and pAkt, which was correlated with the induction of Bax and caspase-3, leading to apoptosis. CONCLUSIONS AS Bcl-2 appeared to be superior to trastuzumab with respect to regulating the signal-transduction pathways involved in breast carcinoma cells. Cancer 2005. © 2005 American Cancer Society. [source] Preclinical evaluation of antisense bcl -2 as a chemosensitizer for patients with gastric carcinomaCANCER, Issue 10 2004Ph.D., Ryungsa Kim M.D. Abstract BACKGROUND Because bcl -2 is a critical factor for anticancer drug-induced apoptosis, the authors conducted a preclinical evaluation of antisense (AS) bcl -2 as an enhancer of the chemotherapeutic effect in the treatment of patietns with gastric carcinoma. METHODS AS bcl -2 was used with 18-mer phosphorothiated oligonucleotides in the MKN-45 gastric carcinoma cell line. Drug sensitivity in vitro was evaluated using the methyl-thiazoldiphenyl tetrazolium assay, and antitumor effects in vivo were evaluated using the nude mouse xenograft. Apoptosis was determined with the terminal deoxyuridine triphosphate nick-end labeling assay. AS bcl -2 in vitro was treated with lipofectin, whereas it was administered intraperitoneally for 6 consecutive days twice every 2 weeks in vivo. Anticancer drugs were administered intraperitoneally four times per week. RESULTS bcl -2 was down-regulated to 60% of its initial value after treatment with 1.0 ,M AS bcl -2 compared with the controls of random and mismatched oligonucleotides. Drug sensitivity to doxorubicin, cisplatin, and paclitaxel (TXL) was increased 3,4-fold when used in combination with AS bcl -2, which was determined with 50% inhibitory concentration values, compared with the control group. Increased drug sensitivity was associated with apoptosis, which increased in Bax and poly-adenosine diphosphate (ADP-ribose) polymerase and decreased in phosphorylated Akt (pAkt). The antitumor effect of cisplatin and TXL in vivo was enhanced significantly in combination with AS bcl -2. Down-regulation of bcl -2 was observed on Day 4 after the treatment with AS bcl -2. CONCLUSIONS Combination treatment with AS bcl -2 and anticancer drugs, including cisplatin and TXL, may be a new strategy for enhancing chemotherapeutic effects in the treatment of gastric carcinoma. Cancer 2004. © 2004 American Cancer Society. [source] Cardioprotection from ischemia-reperfusion injury due to Ras-GTPase inhibition is attenuated by glibenclamide in the globally ischemic heartCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2007Ibrahim Al-Rashdan Abstract The present study was designed to see if acute local inhibition of Ras-GTPase before or after ischemia (during perfusion) would produce protection against ischemia and reperfusion (I/R)-induced cardiac dysfunction. The effect of glibenclamide, an inhibitor of cardiac mitochondrial ATP-sensitive potassium (mitoKATP) channels, on Ras-GTPase-mediated cardioprotection was also studied. A 40,min episode of global ischemia followed by a 30,min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (Pmax) and left ventricular end-diastolic pressure (LVEDP). Perfusion with Ras-GTPase inhibitor FPT III before I/R [FPT(pre)], significantly enhanced cardiac recovery in terms of left ventricular contractility. Pmax was significantly higher at the end of 30,min reperfusion in FPT(pre)-treated hearts compared to pre-conditioned hearts. However, the degree of improvement in left ventricular contractility was significantly less when FPT III was given only after ischemia during reperfusion [FPT(post)]. Combination treatment with FPT III and glibenclamide before I/R resulted in significant reduction of FPT III-mediated cardioprotection. These data suggest that activation of Ras-GTPase signaling pathways during ischemia are critical in the development of left ventricular dysfunction and that opening of mitoKATP channels, at least in part, contributes to cardioprotection produced by Ras-GTPase inhibition. Copyright © 2006 John Wiley & Sons, Ltd. [source] Additive beneficial effects of amlodipine and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive ratsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2009Jing-Chao Lu Summary 1Additive beneficial effects on cardiovascular disease have been reported for amlodipine and atorvastatin. However, it is still unclear whether the combination of amlodipine and atorvastatin has additive beneficial effects on the regression of advanced cardiac hypertrophy in hypertension. In the present study, the effects of the drug combination on advanced cardiac hypertrophy were investigated in elderly spontaneously hypertensive rats (SHR). 2Elderly SHR (36 weeks old) were randomly allocated into four groups of 12: (i) a vehicle-treated control group; (ii) an amlodipine (10 mg/kg per day)-treated group; (iii) an atorvastatin (10 mg/kg per day)-treated group; and (iv) a group treated with a combination of amlodipine and atorvastatin (both at 10 mg/kg per day). Drugs were administered by oral gavage every morning for a period of 12 weeks before hearts were harvested for analysis. 3Combined administration of amlodipine and atorvastatin significantly suppressed cardiomyocyte hypertrophy, interstitial fibrosis and upregulation of hypertrophic and profibrotic genes, and also improved left ventricular diastolic dysfunction to a greater extent than did amlodipine monotherapy. Further beneficial effects of combination therapy on advanced cardiac hypertrophy were associated with a greater reduction of NADPH oxidase-mediated increases in cardiac reactive oxygen species (ROS), rather than decreased blood pressure and serum cholesterol levels. 4To elucidate the underlying molecular mechanisms, we examined cardiovascular NADPH oxidase subunits and found that amlodipine clearly attenuated the expression of p47phox and p40phox and slightly but significantly reduced p22phox and Rac-1 levels in heart tissue. Combination treatment with amlodipine plus atorvastatin led to a further reduction in p22phox, p47phox and Rac-1 protein levels compared with amlodipine alone. 5In conclusion, combined amlodipine and atorvastatin treatment has a greater beneficial effect on advanced cardiac hypertrophy compared with amlodipine monotherapy. The benefits are likely to be related to the additive effects of the drugs on the suppression of NADPH oxidase-mediated ROS generation. [source] Combination treatment with telmisartan and hydrochlorothiazide in black patients with mild to moderate hypertensionCLINICAL CARDIOLOGY, Issue 1 2001Janet B. Mcgill M.D. Abstract Background: Hydrochlorothiazide (HCTZ) is commonly used to treat black patients with hypertension. To avoid the metabolic disturbances associated with high-dose HCTZ, blood pressure control may be achieved by combining low doses with another antihypertensive. Hypothesis: The study was undertaken to assess the tolerability and antihypertensive dose-response efficacy of telmisartan and HCTZ and their combination in black patients with mild to moderate hypertension (mean supine blood pressure 140/95-200/114 mmHg). Methods: Following a 4,week, single-blind, placebo run-in period, 222 black patients were randomized to once-daily treatment with one of 20 different double-blind combinations of telmisartan (0, 20, 40, 80, 160 mg) and HCTZ (0, 6.25, 12.5, 25 mg) for 8 weeks. Blood pressure was measured at baseline and after 2, 4, and 8 weeks. Results: Telmisartan 80 mg/HCTZ 12.5 mg reduced supine trough diastolic blood pressure (DBP),primary efficacy parameter,by 13.3 mmHg, and supine trough systolic blood pressure (SBP) by 21.5 mmHg. These reductions represented benefits of 13.7/8.7 mmHg over telmisartan 80 mg and 12.3/8.1 mmHg over HCTZ 12.5 mg(p<0.01). Telmisartan 40 mg/HCTZ 12.5 mg reduced supine trough SBP/DBP by 14.3/10.0 mmHg, amounting to 12.3/3.3 mmHg more than telmisartan 40 mg and 5.1/4.8 mmHg more than HCTZ 12.5 mg, This reached significance for the comparisons with telmisartan 40 mg for SBP and HCTZ 12.5 mg for DBP (p,0.05). A response surface analysis and therapeutic response rates confirmed the additive antihypertensive effects of telmisartan and HCTZ. All treatments were well tolerated, with side-effect profiles comparable with placebo. Adverse events were mainly transient and of mild to moderate severity. Conclusions: Telmisartan 80 mg combined with HCTZ 12.5 mg is effective and well tolerated in black patients with mild to moderate hypertension, providing greater antihypertensive activity than the corresponding monotherapies. [source] Methylseleninic acid enhances the effect of etoposide to inhibit prostate cancer growth in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Oscar Gonzalez-Moreno Abstract New therapeutic agents are needed for the treatment of androgen-independent prostate cancer (PrCa). We have investigated the effect of methylseleninic acid (MSA) on tumor stage-specific prostate cells derived from the C3 (1)/Tag model for PrCa: Pr111, a slow-growing and nontumorigenic cell line isolated from a prostate intraepithelial neoplasia lesion; Pr14, a tumorigenic line derived from a primary tumor; and Pr14C1, a sub-clone of Pr14 explanted from a lung metastasis. We demonstrate that MSA strongly inhibits cell growth and induces apoptosis in C3 (1)/Tag tumor cells, in a dose-dependent manner. A decrease in phosphorylated ERK1/2 and AKT was also found in tumor cells, but not in Pr111. Microarray analysis using affymetrix showed that the number of genes with an altered expression in tumor cells is significantly higher (p < 0.01) than in nontumoral cells. Pathways analyses revealed a decrease in the expression of genes involved in metabolism (Fabp5, Cyba), signal transduction (ERK, AKT), angiogenesis (neuropilin-1, Flt-4) and transcription (cAMP response element-binding protein) in tumor cells. The expression of neuropilin-1, a protein involved in VEGF signaling and tumor angiogenesis, was 97-fold repressed in Pr14 cells treated with MSA. Combination treatments using low doses of etoposide or taxotere (docetaxel), plus low doses of MSA revealed a strong enhancement of cell growth inhibition and apoptosis in tumor cells. Our in vivo studies using Pr14 cells xenografted into nude mice demonstrated that MSA significantly enhances the chemotherapeutical effect of etoposide, resulting in 78.3% tumor growth inhibition. These results suggest that MSA could be used against PrCa to enhance the effect of etoposide. © 2007 Wiley-Liss, Inc. [source] Meta-analysis of the effectiveness of psychological and pharmacological treatments for binge eating disorderINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 3 2010Silja Vocks PhD Abstract Objective: The aim of this study was to compute and compare mean effects of various treatments for binge eating disorder. Method: A total of 38 studies with 1973 participants fulfilled the defined inclusion criteria. Effect sizes, odds ratios, and simple rates were integrated in fixed and random (mixed) effects categorical models. Results: From randomized controlled trials, psychotherapy and structured self-help, both based on cognitive behavioral interventions, were found to have large effects on the reduction of binge eating. Regarding pharmacotherapy, mainly comprising antidepressants, randomized controlled trials revealed medium effects for the reduction of binge eating. Uncontrolled studies on weight-loss treatments demonstrated moderate reductions of binge eating. Combination treatments did not result in higher effects compared with single-treatment regimens. Except for weight-loss treatment, none of the interventions resulted in a considerable weight reduction. Discussion: Psychotherapy and structured self-help, both based on cognitive-behavioral interventions, should be recommended as the first-line treatments. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2010 [source] Managing amyotrophic lateral sclerosis: Slowing disease progression and improving patient quality of life,ANNALS OF NEUROLOGY, Issue S1 2009Benjamin Rix Brooks MD It is now possible to slow the disease progression of amyotrophic lateral sclerosis (ALS), but documented improvement in the quality of life of ALS patients has been difficult to quantitate. Putative mechanisms involved in motor neuron degeneration in ALS include oxidative damage, mitochondrial dysfunction, neuroinflammation, growth factor deficiency, and glutamate excitotoxicity. Several pharmacological agents that target these potential targets have demonstrated therapeutic potential in animal models with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Many treatments that have been moderately effective in this animal model have not been successfully translated into effective treatments for humans with ALS. Only the glutamate modulator riluzole has demonstrated efficacy in clinical trials and is approved for treating ALS. Combination treatments may represent a potential therapeutic strategy to more robustly prolong life and preserve function, but only vitamin E with riluzole has been formally studied in clinical trials, and to date, no combination treatments have been found to be more effective than currently available single agents. Ann Neurol 2009;65 (suppl):S17,S23 [source] Combined Ultrapulse CO2 Laser and Q-Switched Alexandrite Laser Compared with Q-Switched Alexandrite Laser Alone for Refractory Melasma: Split-Face DesignDERMATOLOGIC SURGERY, Issue 1 2003Suhattaya Angsuwarangsee MD Background. Melasma is common and can cause major psychological impact. To date, the mainstay of treatment, including various hypopigmenting agents and chemical peels, is ineffective and can cause adverse effects. Laser is a new approach and is yet to be explored for its efficacy and safety. Objective. To compare combined Ultrapulse CO2 laser and Q-switched alexandrite laser (QSAL) with QSAL alone in the treatment of refractory melasma. Methods. Six Thai females were treated with combined Ultrapulse CO2 laser and QSAL on one side of the face and QSAL alone on the other side. The outcome was evaluated periodically for up to 6 months using the modified Melasma Area and Severity Index score and the modified Melasma Area and Melanin Index score. Results. The side with combination treatment had a statistically significant reduction of both scores. On the QSAL side, the score reduction was not significant. Two cases developed severe postinflammatory hyperpigmentation and were effectively treated with bleaching agents. Transient hypopigmentation and contact dermatitis were observed with the combination treatment side. Conclusions. Combined Ultrapulse CO2 laser and QSAL showed a better result than QSAL alone but was associated with more frequent adverse effects. Long-term follow-up and a larger number of cases are required to determine its efficacy and safety for refractory melasma. [source] Antipsychotic combination therapy in schizophrenia.ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002A review of efficacy, risks of current combinations Objective:, To review the literature on efficacy and risks of combining antipsychotics (atypical with atypical or conventional) and suggest a rationale and strategies for future clinical trials. Method:, A computerized Medline search supplemented by an examination of cross-references and reviews was performed. Results:, Empirical evidence for the efficacy of combining antipsychotics is too limited to draw firm conclusions. The practice of augmenting clozapine with more ,tightly bound' D2 receptor antagonists as exemplified by risperidone augmentation of clozapine has some empirical and theoretical support. The risks of augmentation strategies have not been studied systematically. No study has examined the economic impact of combination treatment. Conclusion:, Further trials of antipsychotic combination therapies are needed before this currently unsupported practice can be recommended. Rationales for combination treatment include a broadening of the range of receptor activity or an increase in D2 receptor occupancy with certain atypical agents. Trial methodology needs to take into account subject characteristics, duration of treatment, optimization of monotherapy comparators, and appropriate outcome measures. [source] Examination of intravenous and intra-CSF protein delivery for treatment of neurological diseaseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2009Kim M. Hemsley Abstract Mucopolysaccharidosis type IIIA is a neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Absent or greatly reduced activity of sulphamidase, a lysosomal protein, results in intracellular accumulation of heparan sulphate. Subsequent neuroinflammation and neurodegeneration typify this and many other lysosomal storage disorders. We propose that intra-cerebrospinal fluid protein delivery represents a potential therapeutic avenue for treatment of this and other neurodegenerative conditions; however, technical restraints restrict examination of its use prior to adulthood in mice. We have used a naturally-occurring Mucopolysaccharidosis type IIIA mouse model to determine the effectiveness of combining intravenous protein replacement (1 mg/kg) from birth to 6 weeks of age with intra-cerebrospinal fluid sulphamidase delivery (100 ,g, fortnightly from 6 weeks) on behaviour, the level of heparan sulphate-oligosaccharide storage and other neuropathology. Mice receiving combination treatment exhibited similar clinical improvement and reduction in heparan sulphate storage to those only receiving intra-cerebrospinal fluid enzyme. Reductions in micro- and astrogliosis and delayed development of ubiquitin-positive lesions were seen in both groups. A third group of intravenous-only treated mice did not exhibit clinical or neuropathological improvements. Intra-cerebrospinal fluid injection of sulphamidase effectively, but dose-dependently, treats neurological pathology in Mucopolysaccharidosis type IIIA, even when treatment begins in mice with established disease. [source] Rational Combination Therapy in Refractory MigraineHEADACHE, Issue 6 2008B. Lee Peterlin DO Refractory migraine (RM) headaches pose important treatment challenges to the patients who live with them and the clinicians who try to treat them. Defined based on the lack of response to acute, preventive, and nonpharmacologic treatment, RM is often treated with a combination of treatments. Although combination therapy for RM has not been systematically studied in randomized trials, clinical experience suggests that a rational approach to RM treatment, utilizing a combination of treatments, may be effective where monotherapy has failed. In this article we briefly identify patient populations appropriate for more aggressive migraine prevention with combination therapy. We then discuss modifiable risk factors and comorbidities in migraine and then focus on the use of rational combination therapy, as well as the duration migraine preventatives should be considered for use. Future research is needed to evaluate the full potential of rational combination treatment as a strategy for treating and ultimately preventing RM. [source] Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta,,HEPATOLOGY, Issue 3 2006Grazia Anna Niro Therapy of chronic hepatitis delta with standard interferon therapy has met with limited efficacy. This study was designed to examine the efficacy and safety of peginterferon with or without ribavirin. Thirty-eight serum hepatitis B surface antigen- and HDV RNA-positive patients with alanine aminotransferase (ALT) more than 1.5 times the upper normal limit received peginterferon alpha-2b (1.5 ,g/kg) alone as monotherapy (n = 16) or in combination with ribavirin (n = 22), for 48 weeks. Thereafter, all the patients were maintained on peginterferon for 24 weeks and followed for 24 weeks off therapy. The primary end point studied was the virological and biochemical response at the end of follow-up. HDV RNA was determined by single or nested polymerase chain reaction assays. Twenty-seven patients (71%), 11 receiving monotherapy and 16 receiving the combination treatment, completed the follow-up. At the end of treatment, a virological response was observed in 3 of the patients treated with peginterferon (19%) and in 2 of the patients treated with combination therapy (9%), and a biochemical response was observed in 6 (37.5%) and 9 patients (41%), respectively. In nonresponders, ALT diminished from a mean of 174 ± 53 to 86 ± 41 IU/L. At the end of follow-up, serum HDV RNA was negative in 8 patients (21%), and a biochemical response was detected in 10 patients (26%). Treatment was discontinued in 25% of the patients, and dosing was modified in 58%. In conclusion, a prolonged course of peginterferon alpha-2b resulted in clearance of serum HDV RNA and ALT normalization in a fifth of patients with chronic hepatitis D, while ribavirin had no effect on the viral clearance rate. Overall tolerance of therapy was poor. (HEPATOLOGY 2006;44:713,720.) [source] A pilot study of interferon alfa and ribavirin combination in liver transplant recipients with recurrent hepatitis CHEPATOLOGY, Issue 5 2002A. Obaid Shakil Although interferon alfa (IFN-,) and ribavirin are widely used in the treatment of hepatitis C, their role in the transplant recipient is unclear. We conducted a pilot study to determine the efficacy and safety of this therapy in transplant recipients with recurrent hepatitis C. Patients at least 6 months posttransplantation were treated with IFN-, 3 million units 3 times a week subcutaneously and ribavirin 800 mg daily by mouth for 48 weeks followed by ribavirin monotherapy for 24 weeks. The primary end point was sustained virologic response, and secondary end points included biochemical, virologic, and histologic responses at the end of combination treatment. Thirty-eight patients initiated therapy but 16 withdrew due to adverse effects, including 2 with myocardial infarction. Median age was 50 years; 74% were men, and 91% had genotype 1. The median interval between transplantation and enrollment was 23 months. On an intention-to-treat basis, 7 patients (18%) had a biochemical and 5 (13%) had a virologic response at the end of combination treatment. Inflammatory activity did not change, but fibrosis worsened in virologic nonresponders. Ribavirin maintenance caused a further decrease in serum alanine aminotransferase levels, but hepatitis C virus (HCV) RNA levels increased. Only 2 of the 38 patients (5%) had a sustained virologic response. Several patients required treatment with erythropoietin for anemia. In conclusion, IFN-, and ribavirin are effective in a small proportion of liver allograft recipients with recurrent hepatitis C. Adverse effects occur commonly, requiring dose reductions and treatment withdrawal. [source] Management of hepatitis C; Report of the Consensus Meeting at the 45th Annual Meeting of the Japan Society of Hepatology (2009)HEPATOLOGY RESEARCH, Issue 4 2010Izumi Namiki The consensus meeting for the diagnosis, management and treatment for hepatitis C was held in 45th annual meeting for the Japan Society of Hepatology (JSH) in June 2009 where the recommendations and informative statements were discussed including organizers and presenters. The Several important informative statements and recommendations have been shown. This was the fourth JSH consensus meeting of hepatitis C, however, the recommendations have not been published in English previously. Thus, this is the first report of JSH consensus of hepatitis C. The rate of development of hepatocellular carcinoma (HCC) in HCV-infected patients in Japan is higher than in the USA, because the average age of the HCV-infected patients is greater and there are more patients with severe fibrosis of the liver than in the USA. In Japan, more than 60% of HCV-infected patients are genotype 1b infection, and they show lower response to perinterferon and ribavirin combination treatment. To improve the response rate is also an important issue in our country. To establish the original recommendations and informative statements to prevent the development of HCC is a very important issue in Japan. [source] Effect of risperidone on plasma catecholamine metabolites and brain-derived neurotrophic factor in patients with bipolar disordersHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2006Reiji Yoshimura Abstract A combination treatment with a mood stabilizer and an antipsychotic drug is often used in as many as 90% of subjects with acute mania. Recently, augmentation therapy with atypical antipsychotics has been investigated in both the acute and long-term treatment of bipolar disorder with or without psychosis. In the present study, the authors investigated the efficacy of risperidone treatment for both acute manic and depressive episodes in bipolar disorder. Eighteen patients (M/F: 8/10, age: 34,±,15,yr) who met the DSM-IV criteria for bipolar I disorder (12 cases of manic episodes, 6 cases of depressive episodes) with risperidone treatment were evaluated regarding their clinical improvement using the Young Mania rating Scale (YMRS) and the Hamilton rating Scale for Depression (Ham-D). Plasma concentrations of HVA and MHPG were analyzed by HPLC-ECD and plasma brain-derived neurotrophic factor (BDNF) levels were detected by sandwich ELISA. The mean scores of the YMRS were 22, 18, 12, 8, and 5 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The mean scores of the Ham-D were 24, 25, 21, 21, and 19 at time points before and 1, 2, 3, and 4 weeks after the risperidone administration, respectively. The plasma levels of HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) were observed to have decreased 4 weeks after risperidone administration in manic patients. The levels did not change in depressive patients. The plasma levels of BDNF were decreased in depressive patients compared with manic patients or healthy controls. However, the administration of risperidone did not alter plasma BDNF levels. Copyright © 2006 John Wiley & Sons, Ltd. [source] Efficacy of an esfenvalerate plus methoprene aerosol for the control of eggs and fifth instars of Plodia interpunctella (Lepidoptera: Pyralidae)INSECT SCIENCE, Issue 1 2010Emily A. Jenson Abstract, Aerosol insecticides may provide an alternative to fumigants for control of the Indianmeal moth, Plodia interpunctella (Hübner), the Indianmeal moth, a major insect pest of stored processed food. In this study, eggs and larvae (5th instars) of P. interpunctella were exposed to aerosol applications of the pyrethroid esfenvalerate and insect growth regulator methoprene, alone and in combination, in open and obstructed positions inside small sheds. When larvae were exposed to methoprene alone, adult emergence from those exposed larvae was 7.1%± 1.5%. In contrast, adult emergence was 92.5%± 3.5% when larvae were exposed to esfenvalerate alone. When eggs were exposed to methoprene, adult emergence of those exposed eggs was approximately 75%; however, when eggs were exposed to esfenvalerate, adult emergence was approximately 35%. In the combination treatment of methoprene plus esfenvalerate at their respective label rates, adult emergence following larval exposure was 0.91%± 0.61% compared to 16.3%± 9.6% when eggs were exposed. Based on our results, methoprene alone is highly effective in reducing adult emergence after larval exposure. However, it is not as effective on eggs as esfenvalerate. A combination treatment of esfenvalerate plus methoprene could be used to control eggs and the wandering-phase larval stages of P. interpunctella. An economic risk analysis also supports a strategy of combining methoprene and esfenvalerate. [source] The combination of epigallocatechin gallate and curcumin suppresses ER,-breast cancer cell growth in vitro and in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 9 2008Tiffany J. Somers-Edgar Abstract Both epigallocatechin gallate (EGCG) and curcumin have shown efficacy in various in vivo and in vitro models of cancer. This study was designed to determine the efficacy of these naturally derived polyphenolic compounds in vitro and in vivo, when given in combination. Studies in MDA-MB-231 cells demonstrated that EGCG + curcumin was synergistically cytotoxic and that this correlated with G2/M-phase cell cycle arrest. After 12 hr, EGCG (25 ,M) + curcumin (3 ,M) increased the proportion of cells in G2/M-phase to 263 ± 16% of control and this correlated with a 50 ± 4% decrease in cell number compared to control. To determine if this in vitro result would translate in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with curcumin (200 mg/kg/day, po), EGCG (25 mg/kg/day, ip), EGCG + curcumin, or vehicle control (5 ml/kg/day, po) for 10 weeks. Tumor volume in the EGCG + curcumin treated mice decreased 49% compared to vehicle control mice (p < 0.05), which correlated with a 78 ± 6% decrease in levels of VEGFR-1 protein expression in the tumors. Curcumin treatment significantly decreased tumor protein levels of EGFR and Akt, however the expression of these proteins was not further decreased following combination treatment. Therefore, these results demonstrate that the combination of EGCG and curcumin is efficacious in both in vitro and in vivo models of ER,- breast cancer and that regulation of VEGFR-1 may play a key role in this effect. © 2007 Wiley-Liss, Inc. [source] Combining adenoviral oncolysis with temozolomide improves cell killing of melanoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 12 2007Christina Quirin Abstract Oncolytic Adenoviruses are emerging agents for treatment of cancer by tumor-restricted virus replication, cell lysis and virus spread. Clinical studies with first generation oncolytic adenoviruses have revealed that an increased potency is warranted in order to achieve therapeutic efficacy. One approach towards this end is to combine adenoviral oncolysis with chemotherapy. Here, a fundamental requirement is that chemotherapy does not interfere with adenovirus replication in cancer cells. We have previously developed a melanoma-targeted oncolytic adenovirus, Ad5/3.2xTyr, which features tyrosinase promoter regulated replication and enhanced cell entry into melanoma cells. In this study, we investigated a combination treatment of melanoma cells with Ad5/3.2xTyr and temozolomide (TMZ), which produces the same active metabolite as Dacarbazine/DTIC, the standard chemotherapy for advanced melanoma. We report that TMZ does not inhibit adenovirus replication in melanoma cells. Additive or synergistic cell killing of melanoma cells, dependent on the cell line used, was observed. Enhanced cell binding was not responsible for synergism of adenoviral oncolysis and TMZ treatment. We rather observed that higher numbers of virus genomes are produced in TMZ-treated cells, which also showed a cell cycle arrest in the G2 phase. Our results have important implications for the clinical implementation of adenoviral oncolysis for treatment of malignant melanoma. It suggests that such studies are feasible in the presence of TMZ or DTIC chemotherapy and recommends the investigation of a viro-chemo combination therapy. © 2007 Wiley-Liss, Inc. [source] Enhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Maarten L. Janmaat Abstract In this study, we have characterized a panel of NSCLC cell lines with differential sensitivity to gefitinib for activating mutations in egfr, pik3ca, and k-ras, and basal protein expression levels of PTEN. The egfr mutant NSCLC cell line H1650 as well as the egfr wild type cell lines H292 and A431 were highly sensitive to gefitinib treatment, indicating that other factors determine gefitinib-sensitivity in egfr wild type cells. Activating k-ras mutations were specifically detected in gefitinib-resistant cells, suggesting that the occurrence of k-ras mutations is correlated with resistance to EGFR antagonists. No pik3ca mutations were detected within the panel of cell lines, and PTEN protein expression levels did not correlate with gefitinib sensitivity. Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib-sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib-resistance of NSCLC cell lines. Gefitinib-resistant NSCLC cell lines, showing EGFR-independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Additive cytotoxicity was observed in A549 cells co-treated with gefitinib and the MEK inhibitor U0126 or the farnesyl transferase inhibitor SCH66336 and in H460 cells treated with gefitinib and the PI3K inhibitor LY294002, but not in H460 cells treated with gefitinib and rapamycin. These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. © 2005 Wiley-Liss, Inc. [source] Cyclooxygenase-2 inhibitor celecoxib augments chemotherapeutic drug-induced apoptosis by enhancing activation of caspase-3 and -9 in prostate cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 3 2005Devendra S. Dandekar Abstract Many tumors constitutively express high levels of the inducible form of proinflammatory enzyme, cyclooxygenase-2 (COX-2). Increased COX-2 expression is associated with tumor cell resistance to many cytotoxic chemotherapy drugs. Furthermore, increased resistance to cytotoxic antitumor drugs is also known to be dependent on associated stromal cells in many tumors. We investigated whether prostate tumor-associated stromal cells, marrow-derived osteoblasts, affect cytotoxicity of 2 antitumor drugs, COL-3 and docetaxel (TXTR), and whether it is dependent on COX-2 activity. We further examined whether inhibiting the activity of COX-2 negate the stroma-induced decrease in drug sensitivity in tumor cells. COX-2-specific inhibitor celecoxib (CXB) was used to inhibit COX-2 activity and associated alteration in cell death signaling was investigated. Coculturing PC-3ML cells with osteoblasts decreased the cytotoxicity of the tested antitumor drugs and was associated with increased COX-2 activity in PC-3ML cells. A significant decrease in drug-induced PGE2 increase and an increase in cytotoxicity were observed when cells were treated with COL-3 or TXTR combined with CXB. Cytotoxicity of single or combination treatment increased apoptosis, which was associated with caspase-3 and -9 activation, PARP cleavage, increased BAD protein, but decreased protein levels of XIAP and BCL- xL. Oral administration of CXB (40 mg/kg) to mice with PC-3ML tumors for 42 days increased tumor latency, decreased tumor growth and enhanced tumor control with COL-3 or TXTR. Overall, a synergistic enhancement of antitumor activity in combination treatment was observed in vitro and an additive effect in vivo. These observations suggest a potential clinical use of combined dosing of COX-2 inhibitors and cytotoxic drugs at lower, nontoxic dose than currently used to treat advanced prostate cancer. © 2005 Wiley-Liss, Inc. [source] Oral fish cartilage polysaccharides in the treatment of photoageing: biophysical findingsINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2002F. Distante Synopsis The topically applied cosmetic products can be helpful in improving the aged skin condition. The present study shows how oral fish-cartilage food supplementation can be helpful in improving the treatment of ageing skin. A total of 30 healthy women with signs of skin ageing were studied. Fifteen of the women were treated with a food supplement based on polysaccharides derived from the fish cartilage and a natural mix of antioxidants for 2 months and the other 15 with a placebo. Clinical evaluation and biophysical parameters related to skin function and wrinkle severity, such as silicone replica, skin thickness, mechanical properties, skin colour and capacitance, were measured. The results showed statistically significant changes in the active-treated group in comparison to the placebo. In particular, dermal thickness (treatment: from 1.13 to 1.23 mm; P < 0.001), skin wrinkling (treatment: from 9.5 to 3.5 Ra; P< 0.002), skin colour (treatment: brighter and less pigmented; P < 0.02) and viscoelasticity (treatment: from 0.70 to 0.97%; P < 0.02) showed considerable improvement. Most of these parameters are related to changes occurring within the dermal matrix, which is improved after the treatment, whereas most of the topically applied cosmetic products have a short-term effect on superficial structures. A combination treatment (oral and topical) can be more effective in reducing the signs of skin-ageing. Résumé Les produits cosmétiques en topiques locaux ont montré leur efficacité pour ralentir le vieillissement cutané. Cette étude montre qu'un traitement oral, à base de cartilage de poisson sous forme de suppléments nutritifs, peut être un complément efficace dans le traitement du vieillissement cutané. 30 femmes en bonne santé présentant des signes de vieillissement cutané ont été incluses dans notre étude. 15 d'entre elles ont reçu pendant 2 mois une supplémentation alimentaire à base de polysaccharides dérivés de cartilage de poisson, associée à un mélange normal d'antioxydants. Les 15 autres femmes ont été traitées avec un placebo. Les paramètres cliniques et biophysiques suivants, évaluant la fonction de la peau et la sévérité des rides ont été mesurés: réplica?? de silicone, épaisseur de la peau, propriétés mécaniques, couleur de peau et état d'hydratation cutanée. Les résultats ont mis en évidence des changements significatifs entre le groupe placebo et le groupe traité pour les paramètres étudiés. En particulier, l'épaisseur cutanée (traitement: de 1.13 à 1.23 mm; P < 0.001), les rides (traitement: de 9.5 à,3.5 Ra; P < 0.002), la couleur de la peau (traitement: plus claire et moins pigmentée; P < 0.02) et la visco-élasticité (traitment: de 0.70 à 0.97%; P < 0.02) ont été considérablement améliorées. La plupart de ces paramètres sont liées aux changements qui se produisent en profondeur dans la matrice dermique, alors que la plupart des produits cosmétiques topiques ont un effet à court terme sur les structures superficielles. La combinaison d'un traitement oral associéà un traitement local peut être plus efficace dans la prévention du vieillissement cutané. [source] Modulation of angiogenesis is effective in a model of rheumatoid arthritisJOURNAL OF ANATOMY, Issue 5 2002A. O. Afuwape A feature of rheumatoid arthritis (RA) is prominent hyperplasia of the synovium, which results in an increased distance between the invasive pannus and the existing synovial vasculature. Concomitantly the hyperplastic tissue imposes an augmented metabolic demand on the pre-existing vasculature. As a consequence the synovium in RA becomes hypoxic, resulting in an increased rate of formation of new blood vessels, to supply nutrients and oxygen. Targeting the vasculature in RA is a potential therapeutic approach in RA. VEGF, a key vascular permeability and angiogenic factor, is expressed in RA. In this study we utilised adenovirus expressing the secreted form of the extracellular domain of the Flt-1 VEGF receptor (sFlt-1) to inhibit VEGF in the collagen-induced arthritis (CIA) model, to determine whether blocking the effects of vegf might be an effective treatment for RA. AdvsFlt-1, administered intravenously on the first day of arthritis, significantly suppressed CIA. For example, on d 6 of arthritis the mean increase in paw thickness, which reflects oedema, for untreated and null adenovirus-treated animals was 0.23 ± 0.05 mm and 0.38 ± 0.08, respectively, compared to 0.07 ± 0.05 for AdvsFlt-1-treated mice (P < 0.001 vs. Adv0-treated and untreated mice by 2-way anova). Western blot analyses revealed the presence of a 100-kDa band, corresponding to human sFlt-1, in liver extracts from arthritic mice infected with AdvsFlt-1 at 24 h but not 72 h after infection. This band was absent in liver extracts from Adv0-infected mice and all synovial extracts. Measurement of protein levels by ELISA demonstrated the presence of sFlt-1 in liver, synovium and serum, although levels declined by 72 h post infection. These data suggest efficient but transient expression of sFlt-1. Sera from adenovirus infected mice were found to contain antiviral antibodies and additionally, sera from AdvsFlt-1-infected but not Adv0-infected mice recognised human recombinant sFlt-1. These observations demonstrate that adenoviral mediated delivery of human sFlt-1 leads to transient gene expression and suppression of CIA. This effect is reduced later in the course of disease due to the expression of antiadenovirus as well as antisFlt-1 antibodies. Future studies will assess the effect of combination treatment, using AdvsFlt-1 together with anti-TNF(antibody, to prolong the beneficial effects of VEGF blockade. These results suggest that blocking the pro-angiogenic and permeability action of VEGF may be beneficial for treatment of RA. [source] Preparation and characterization of PDLC films formed using a two-step procedureADVANCES IN POLYMER TECHNOLOGY, Issue 1 2007Yu-Che Hsiao Abstract A novel polymer-dispersed liquid crystal composite film was prepared using liquid crystal and dual resins, namely, UV-curable urethane diacrylate and thermo-curable epoxy, with a fixed LC content of 50 wt%. A combination treatment of UV irradiation and heat was performed in sequential steps. At first, the urethane diacrylate resin was cross-linked through UV irradiation and a pre-UV-cured film was formed. Then, the pre-UV-cured film was heat treated for curing the thermo-curable epoxy resin. As the thermal polymerization continued, LC droplets were formed and became embedded within the polymer matrix. PDLC films obtained from the polymer matrix with refractive indices in a range from 1.511 to 1.523 (1.517 ± 0.006) have optimal electro-optical properties. Films with a refractive index higher than 1.523 have high contrast ratio (CR), threshold voltage (Vth), and V90, whereas those with a low refractive index of 1.508 have low CR, Vth, and V90. In this study, we found that PDLC composite films with optimal compositions prepared by dual resins (UV/thermal) have good electro-optical properties. © 2007 Wiley Periodicals, Inc. Adv Polym Techn 26:14,20, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20087 [source] Striae treated by a novel combination treatment , sand abrasion and a patent mixture containing 15% trichloracetic acid followed by 6,24 hrs of a patent cream under plastic occlusionJOURNAL OF COSMETIC DERMATOLOGY, Issue 2 2003M A Adatto Summary Background, Striae are a common cosmetic problem, especially for women. Little has been published about chemical peel treatment of striae. Objective, To recount 5 years experience of striae treated by a novel combination treatment , sand abrasion and a patent mixture containing 15% trichloracetic acid followed by 6,24 h of a patent cream under plastic occlusion. Materials and methods, Sixty-nine females of various phototypes, aged 14,63 years, were treated at various anatomical sites: abdomen (43), lateral thighs (11), breasts (4), back (3), waist (3) and others (5). Striae of all types: fresh, old, mild and severe, were treated. Average follow up was 18 months. Results, After 1,8 treatments (median 4.2), appearance of the striae improved by 70%. Results were best in fresher and more superficial striae. Conclusions, A novel combination treatment is reported which safely, predictably and effectively improved striae in all skin types. [source] The Effects of Irradiation, High Hydrostatic Pressure, and Temperature during Pressurization on the Characteristics of Cooked-reheated Salmon and Catfish FilletsJOURNAL OF FOOD SCIENCE, Issue 1 2003D.R. McKenna ABSTRACT: Fully-cooked salmon and catfish fillets were treated by ionizing radiation (0, 3, or 6 kGy), high hydrostatic pressure (HHP) (0, 414, or 690 MPa), 2 different temperatures during pressurization (ambient-HHP approximately equal to 21 °C, or heated-HHP = 70 °C), and combinations of the treatments. Kramer shear values increased for salmon and catfish fillets treated by HHP, heated-HHP, and a combination treatment. Tenderness and juiciness scores of salmon and catfish fillets were lower with HHP, heated-HHP, and a combination treatment. Irradiation decreased CIE a* values of salmon, and CIE b* values of salmon and catfish. Irradiation increased tenderness and juiciness scores of salmon and increased flavor intensity of catfish. [source] | ||||||||||||||||||||||||||||||||||||||||||||||