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Combined Treatment (combined + treatment)
Selected AbstractsCombined Treatment of Perchlorate and RDX in Ground Water Using a Fluidized Bed ReactorGROUND WATER MONITORING & REMEDIATION, Issue 3 2007Mark E. Fuller A bench-scale study was conducted to assess the effectiveness of biological treatment of comingled perchlorate and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in ground water using fluidized bed reactors (FBRs). In addition, the ability of FBRs to treat low concentrations of perchlorate was examined. Pilot-scale FBRs were fed either acetic acid or molasses as an electron donor to facilitate simultaneous perchlorate and RDX reduction. The acetic acid-fed FBR consistently removed perchlorate from an influent level of 100 ,g/L to below 6 ,g/L, and values below the method detection limit of 1 ,g/L occurred approximately 70% of the time. RDX breakthrough from all FBRs was minimal due to sorption of the explosive on the granulated activated carbon media, but mass balance calculations indicated that more than 99.5% of the total RDX entering the acetic acid-fed FBR was biologically degraded. Approximately 80% of the RDX fed to the control FBR (i.e., no substrate addition) was accounted for at the end of the study; the remainder was assumed to have been degraded. Molasses was much less effective than acetic acid as an electron donor for treatment of perchlorate and RDX. This work demonstrates that combined treatment of perchlorate and RDX is feasible using FBR technology, and that very low levels of perchlorate (less than 100 ,g/L) can be effectively treated in an FBR. [source] Amelioration of Cadmium-Induced Oxidative Stress, Impairment in Lipids and Plasma Lipoproteins by the Combined Treatment with Quercetin and ,-Tocopherol in RatsJOURNAL OF FOOD SCIENCE, Issue 7 2010S. Milton Prabu Abstract:, Cadmium (Cd) exposure results in numerous pathological consequences including oxidative stress and dyslipidemia. The present study was designed to investigate the efficacy of combined treatment with quercetin (QE) and ,-tocopherol (AT) against Cd-induced oxidative stress and alterations in lipids and lipoproteins in the plasma and liver of rats. Oral administration of Cd (5 mg/kg bw/d) for 4 wk has shown a significant (P < 0.05) increase in thiobarbituric acid reactive substances (TBARS), lipid hydro peroxides (LOOH), total cholesterol, low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), free fatty acids (FFA), phospholipids (PL), triglycerides (TGs), and the activity of hydroxyl-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) in plasma with a significant (P > 0.05) reduction in the levels of reduced glutathione (GSH), high density lipoprotein cholesterol (HDL-C), and the activity of lecithin cholesterol acyl transferase (LCAT) in plasma. In addition, the levels of hepatic thiobarbituric acid reactive substances (TBARS), LOOH, conjugated dienes (CD), protein carbonyls (PC), and the activity of HMG-CoA reductase, levels of cholesterol, FFA, and TGs were significantly (P > 0.05) increased and the level of PL is significantly (P > 0.05) decreased along with the decreased activity of LCAT in the liver of Cd-treated rats. Oral supplementation with QE (50 mg/kg bw/d) and AT (50 mg/kg bw/d) for 4 wk in Cd intoxicated rats significantly (P > 0.05) has reduced the plasma levels of TBARS, LOOH, GSH, cholesterol, FFA, TGs, VLDL-C, LDL-C, and the activity of HMG-CoA and significantly (P > 0.05) has increased the activity of LCAT and the plasma levels of HDL-C. The oral supplementation also significantly (P > 0.05) has reduced the hepatic oxidative stress markers, cholesterol, TGs, FFA, and significantly (P > 0.05) has increased the LCAT activity and the PL in liver. Our results indicate that the combined treatment with QE and AT has normalized all the previously mentioned biochemical parameters in Cd-intoxicated rats than the individual treatments. The combined treatment has provided remarkable protection against Cd-induced oxidative stress and alterations in lipid metabolism and, thereby, reduced the Cd-mediated cardiovascular diseases. [source] Antitumour Activity and Side Effects of Combined Treatment with Chitosan and Cisplatin in Sarcoma 180-Bearing MiceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2000YOSHIYUKI KIMURA We examined the possible modulation by chitosan of the antitumour effects and side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed that CDDP had potent antitumour activity when administered orally as well as intraperitoneally. We also compared the antitumour activity and side effects of orally administered CDDP plus orally administered chitosan versus intraperitoneally administered CDDP plus orally administered chitosan in sarcoma 180-bearing mice. When CDDP (1.25 mg kg,1 × 2 day,1) was intraperitoneally administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen urea level), immunotoxicity (the reduction of spleen and thymus weight) and a reduction in body weight resulted. These intraperitoneally administered CDDP-induced side effects were not prevented by oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1) for 14 consecutive days. On the other hand, the side effects such as the reductions of body and spleen weights induced by orally administered CDDP (1.25 mg kg,1 × 2 day,1) were prevented by the oral administration of chitosan (150 mg kg,1 × 2 day,1 and 750 mg kg,1 × 2 day,1). From these results, we conclude that the orally administered chitosan plus CDDP might be useful for the prevention of body weight reduction and immunotoxicity (the reduction of spleen weight) induced by the orally administered CDDP without diminishing antitumour activity. [source] Induction of Primary Cutaneous Melanomas in C3H Mice by Combined Treatment with Ultraviolet Radiation, Ethanol and Aloe Emodin ,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2000Faith M. Strickland ABSTRACT The role of ultraviolet (UV) radiation in the induction of nonmelanoma skin cancer is widely accepted, although its precise contribution to the development of primary cutaneous melanoma skin cancer requires further definition. We found that painting aloe emodin, a trihydroxyanthraquinone from Aloe barbadensis, in ethyl alcohol vehicle on the skin of mice in conjunction with exposure to UVB (280,320 nm) radiation results in the development of melanin-containing skin tumors. C3H/HeN mice were treated thrice weekly with aloe emodin in a 25% ethanol in water vehicle and exposed to 15 kJ/m2 UV radiation. Neither ethanol vehicle nor aloe emodin alone induced skin tumors in the absence of UV radiation. In two separate experiments, 20,30% of the mice treated with a combination of UV radiation and ethanol vehicle and 50,67% of the UV-irradiated animals given aloe emodin in ethanol vehicle developed primary cutaneous melanin-containing tumors. The diagnosis of melanoma was established using Fontana silver stain for melanin; these tumors were negative for vimentin and keratin. Melanin-containing melanosomes were observed by transmission electron microscopy in tumors diagnosed as melanomas. Although the mechanism of carcinogenesis in these mice is currently unknown, our findings have led to the development of the first facile murine model for the induction of primary melanoma. This model has the potential to clarify the role of UV radiation in the etiology of malignant melanoma. [source] Surgery and Adjuvant Radiotherapy in Patients with Cutaneous Head and Neck Squamous Cell Carcinoma Metastatic to Lymph Nodes: Combined Treatment Should be Considered Best Practice,THE LARYNGOSCOPE, Issue 5 2005FRANZCR, Michael J. Veness MMed Abstract Objective: Patients with cutaneous squamous cell carcinoma (SCC) may develop metastatic SCC to nodes in the head and neck. Recent data support best outcome with the addition of adjuvant radiotherapy. This study aims to present further supportive evidence. Study Design: Retrospective chart review. Methods: Patients were identified with metastatic cutaneous SCC to nodes of the head and neck treated with surgery or surgery and adjuvant radiotherapy. Relapse and outcome were analyzed using Cox regression analysis. Disease-free survival and overall survival rates were calculated using Kaplan-Meier survival curves. Results: Between 1980 to 2000, 167 patients were treated with curative intent at Westmead Hospital, Sydney. Median age was 67 years (range, 34,95) in 143 men and 24 women with a minimum follow-up of 24 months. Patients underwent surgery (21/167; 13%), or surgery and adjuvant radiotherapy (146/167; 87%). The majority (98/167; 59%) of metastatic nodes were located in the parotid and/or cervical nodes. The remaining 69 (41%) had metastatic cervical nodes (levels I,V). Forty-seven patients (28%) had recurrences, with the majority (35/47; 74%) as locoregional failures. On multivariate analysis, spread to multiple nodes and single-modality treatment significantly predicted worse survival. Patients undergoing combined treatment had a lower rate of locoregional recurrence (20% vs. 43%) and a significantly better 5-year disease-free survival rate (73% vs. 54%; P = .004) compared to surgery alone. Conclusions: In patients with metastatic cutaneous head and neck SCC, surgery and adjuvant radiotherapy provide the best chance of achieving locoregional control and should be considered best practice. [source] The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: a randomized controlled studyDIABETIC MEDICINE, Issue 5 2004R. Rachmani Abstract Objective The effect of spironolactone, cilazapril and their combination on albuminuria was examined in a randomized prospective study in female patients with diabetes and hypertension. Patients and methods Sixty female diabetic patients aged 45,70 years with blood pressure (BP) 140,180/90,110 mmHg, serum creatinine (sCr) , 160 µmol/l, HbA1c , 10%, and albuminuria were treated by atenolol 12.5,75 mg/d and hydrochlorothiazide 6.25,25 mg/d. Titration-to-target helped to reach BP values , 135/85 mmHg in 46 patients after 12 weeks. These patients were randomized to spironolactone 100 mg/d or cilazapril 5 mg/d for 24 weeks. Then both groups received spironolactone 50 mg/d and cilazapril 2.5 mg/d for 24 weeks. BP was stabilized by tapering the dose of the initial agents. Urinary albumin/creatinine ratio (ACR), BP, K+. sCr and HbA1c were assessed at baseline and at weeks 12, 16, 36 and 60. Results The average BP at week 12 was 128 ± 4/81 ± 3 mmHg and remained constant, in both groups, throughout the study. ACR declined on spironolactone from a median value (range) of 452 (124,1571) to 216 (64,875) mg/g (P = 0.001), and on cilazapril to 302 (90,975) mg/g (P = 0.001). The difference between spironolactone and cilazapril was significant (P = 0.002). Combined treatment resulted in a further modest decline in ACR. Serum creatinine was unaltered by spironolactone and rose slightly (121 to 126 µmol/l, P = 0.02) on cilazapril. Conclusion At the doses tested, spironolactone was superior to cilazapril in reducing albuminuria. Combined administration was more effective than either drug alone. These effects were independent of BP values. Hyperkalaemia was the main side-effect. [source] Combined treatment of achalasia , botulinum toxin injection followed by pneumatic dilatation: long-term resultsDISEASES OF THE ESOPHAGUS, Issue 2 2010R. Kroupa SUMMARY Injection of botulinum toxin (BT) and pneumatic dilatation are available methods in nonsurgical treatment of achalasia. Authors anticipate beneficial effect of prior BT injection on the success of pneumatic dilatation and duration of its effect. There are no long-term data available to assess efficacy of combined treatment. From 1998 to 2007, 51 consecutive patients (20 men and 31 women, age 24,83) with achalasia were included and prospectively followed up. Each patient received injection of 200 IU of BT into the lower esophageal sphincter (LES) during endoscopy and 8 days later pneumatic dilatation (PD) under X-ray control was performed. The follow-up was established every 3 months first year and then annually. The efficacy was evaluated by a questionnaire concerning patient's symptoms and manometry. Results were compared with 40 historical controls (16 men and 24 women, age 26,80) treated by PD alone using the same method and follow-up. Fifty-one patients underwent combined treatment. Four patients failed in follow-up and were not included for analysis. The mean duration of follow-up was 48 months with range 12,96 months. Thirty-four of forty-seven (72%) patients were satisfied with results with none or very rare and mild troubles at the time of the last visit. Forty-one patients were followed up more than 2 years. Effect of therapy lasted in 75% (31/41) of them. In 17 patients, more than 5 years after treatment, effect lasted in 12 (70%). Mean tonus of LES before therapy was 29 mm Hg (10,80), 3 months after therapy decreased to 14 mmHg (5,26). The cumulative 5 years remission rate (±95% CI) in combined treated patients 69% ± 8% was higher than in controls 50% ± 9%; however it, was not statistically significant (P= 0.07). In control group 1, case of perforation (2.5%) occurred. Eight patients (17%) with relapse of dysphagia were referred to laparoscopic Heller myotomy with no surgical complication. The main adverse effect was heartburn that appeared in 17 patients (36%). Initial injection of BT followed by PD seems to be effective for long-term results with fewer complications. But the combined therapy is not significantly superior to PD alone. [source] Chemoresistant tumor cell lines display altered epidermal growth factor receptor and HER3 signaling and enhanced sensitivity to gefitinibINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Tiziana Servidei Abstract Deregulated signaling through the epidermal growth factor receptor (EGFR) is involved in chemoresistance. To identify the molecular determinants of sensitivity to the EGFR inhibitor gefitinib (Iressa, ZD1839) in chemoresistance, we compared the response of matched chemosensitive and chemoresistant glioma and ovarian cancer cell lines. We found that chemoresistant cell lines were 2- to 3-fold more sensitive to gefitinib growth-inhibitory effects, because of decreased proliferation rather than survival. Sensitivity to gefitinib correlated with overexpression and constitutive phosphorylation of HER2 and HER3, but not EGFR, altered HER ligand expression, and enhanced activation of EGF-triggered EGFR pathway. No activating mutations were found in EGFR. Gefitinib fully inhibited EGF-induced and constitutive Akt activation only in chemoresistant cells. In parallel, gefitinib downregulated constitutively phosphorylated HER2 and HER3, and activated GSK3, with a concomitant degradation of cyclin D1. Ectopically overexpressed HER2 on its own was insufficient to sensitize chemonaive cells to gefitinib. pHER3 coimmunoprecipitated with p85-PI3K in chemoresistant cells and gefitinib dissociated these complexes. siRNA-mediated inhibition of HER3 decreased constitutive activation of Akt and sensitivity to gefitinib in chemoresistant cells. Our study indicates that in chemoresistant cells gefitinib inhibits both an enhanced EGF-triggered pathway and a constitutive HER3-mediated Akt activation, indicating that inhibition of HER3 together with that of EGFR could be relevant in chemorefractory tumors. Furthermore, in combination experiments gefitinib enhanced the effects of coadministered drugs more in chemoresistant than chemosensitive ovarian cancer cells. Combined treatment might be therapeutically beneficial in chemoresistant tumors from ovary and likely from other tissues. © 2008 Wiley-Liss, Inc. [source] EGFR tyrosine kinase inhibition radiosensitizes and induces apoptosis in malignant glioma and childhood ependymoma xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Birgit Geoerger Abstract Malignant gliomas and childhood ependymomas have a high rate of treatment failure. Epidermal growth factor receptor (EGFR) activation has been implicated in the tumorigenesis and radioresistance of many cancers, including brain tumors. Therefore, combining EGFR targeting with irradiation is a potentially attractive therapeutic option. We evaluated the tyrosine kinase inhibitor gefitinib for its antitumor activity and potential to radio-sensitize in vivo in two xenograft models: an EGFR amplified glioma and an EGFR expressing ependymoma, both derived from primary tumors. When administered at 100 mg/kg for 5 consecutive days, gefitinib-induced partial tumor regression in all treated EGFR amplified IGRG88 glioma xenografts. The addition of 1 Gy of irradiation prior to gefitinib administration resulted in 5 complete and 4 partial regressions for the 9 treated tumors as well as a significant tumor growth delay of 33 days for the combined treatment compared to 19 days for each therapy alone, suggesting additive antitumor activity. Tumor regression was associated with inhibition of AKT and MAPK pathways by gefitinib. In contrast, the ependymoma IGREP83 was sensitive to irradiation, but remained resistant to gefitinib. Combined treatment was associated with inhibition of radiation-induced MAPK phosphorylation and significant induction of apoptotic cell death though radiation-induced AKT phosphorylation was maintained. Depending on the scheduling of both therapies, a trend towards superior antitumor activity was observed with combined treatment. Thus, EGFR targeting through tyrosine kinase inhibition appears to be a promising new approach in the treatment of EGFR-driven glioma, particularly in combination with radiation therapy. © 2008 Wiley-Liss, Inc. [source] Interactions between N,acetylcysteine and sodium selenite in modulating the clastogenicity of urethane and 2,acetylaminofluorene in miceINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Roumen M. Balansky Abstract Combined treatment with different agents represents a promising approach in cancer chemoprevention. Therefore, it is useful to assess in preclinical models the efficacy of combinations that are selected by taking into account mechanistic considerations. We designed 2 studies evaluating the interaction between N,acetylcysteine (NAC) and sodium selenite (Se), both given with the drinking water to Balb/c mice, in modulating clastogenic effects in bone marrow polychromatic erythrocytes. In a first study, a single i.p. injection of urethane considerably enhanced the frequency of micronucleated cells. While NAC produced a significant inhibition, Se further enhanced urethane clastogenicity. When given in combination at the same doses, NAC prevented the adverse effect of Se. In a second study, a single i.p. injection of 2,acetylaminofluorene enhanced the frequency of micronucleated cells. Se did not reduce this effect to a significant extent, while NAC produced a dose,dependent inhibition. When tested at the lower dose in combination with Se, the protective effect of NAC was unchanged. Especially in association with Se, NAC also prevented the toxicity of 2,acetylaminofluorene by normalizing the ratio of polychromatic to normochromatic erythrocytes. In conclusion, NAC attenuated the clastogenicity of both urethane and 2,acetylaminofluorene and the toxicity of this aromatic amine. In addition, NAC prevented the clastogenic and toxic effects resulting from the interaction of Se with urethane. Together with the findings of previous studies, it appears that, besides its intrinsic protective properties in carcinogenesis, NAC is capable of attenuating the adverse effects of several cytotoxic drugs and chemopreventive agents. © 2003 Wiley-Liss, Inc. [source] Antitumor activity of a novel antisense oligonucleotide against Akt1JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2009Heejeong Yoon Abstract The AKT pathway is an important therapeutic target for cancer drug discovery as it functions as a main point for transducing extracellular and intracellular oncogenic signals. Moreover, alternations of the AKT pathway have been found in a wide range of cancers. In the present study, we found that an Akt1 antisense oligonucleotide (Akt1 AO) significantly downregulated the expression of AKT1 at both the mRNA and protein levels and inhibited cellular growth at nanomolar concentrations in various types of human cancer cells. Combined treatment of Akt1 AO with several cytotoxic drugs resulted in an additive growth inhibition of Caki-1 cells. The in vivo effectiveness of Akt1 AO was determined using two different xenograft nude mouse models. Akt1 AO (30,mg/kg, i.v. every 48,h) significantly inhibited the tumor growth of nude mouse subcutaneously implanted with U251 human glioblastoma cells after 27 days treatment. Akt1 AO (30,mg/kg, i.p continuously via osmotic pump) also significantly inhibited the tumor formation in nude mice implanted with luciferase-expressing MIA human pancreatic cancer cells (MIA-Luc) after 14 days of treatment. The luciferase signals from MIA-Luc cells were reduced or completely abolished after 2 weeks of treatment and the implanted tumors were barely detectable. Our findings suggest that Akt1 AO alone or in combination with other clinically approved anticancer agents should be further explored and progressed into clinical studies as a potential novel therapeutic agent. J. Cell. Biochem. 108: 832,838, 2009. © 2009 Wiley-Liss, Inc. [source] Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l -DOPA-induced dyskinesiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003M. Lundblad Abstract We have examined the ability of KW-6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of l -DOPA in 6-hydroxydopamine-lesioned rats. In animals rendered dyskinetic by a previous course of l -DOPA treatment, KW-6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the severity of dyskinesia when coadministered with l -DOPA. A second experiment was undertaken in order to study the effects of KW-6002 in l -DOPA-naive rats. Thirty-five animals were allotted to four groups to receive a 21-day treatment with: (i) KW-6002 (10 mg/kg/day); (ii) l -DOPA (6 mg/kg/day) i.p.; (iii) KW-6002 plus l -DOPA (same doses as above) or (iv) vehicle. Chronic treatment with KW-6002-only produced a significant relief of motor disability in the rotarod test in the absence of any abnormal involuntary movements. Combined treatment with l -DOPA and KW-6002 improved rotarod performance to a significantly higher degree than did each of the two drugs alone. However, this combined treatment induced dyskinesia to about the same degree as did l -DOPA alone. In situ hybridization histochemistry showed that KW-6002 treatment alone caused an approximately 20% reduction in the striatal levels of preproenkephalin mRNA, whereas neither the coadministration of KW-6002 and l -DOPA nor l -DOPA alone significantly altered the expression of this transcript in the dopamine-denervated striatum. Either alone or in combination with l -DOPA, KW-6002 did not have any modulatory effect on prodynorphin mRNA expression or FosB/,FosB-like immunoreactivity in the dopamine-denervated striatum. These results show that monotreatment with an adenosine A2a receptor antagonist can relieve motor disability without inducing behavioural and cellular signs of dyskinesia in rats with 6-hydroxydopamine lesions. Cotreatment with KW-6002 and l -DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug. [source] Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitisALLERGY, Issue 3 2010A. Nair To cite this article: Nair A, Vaidyanathan S, Clearie K, Williamson P, Meldrum K, Lipworth BJ. Steroid sparing effects of intranasal corticosteroids in asthma and allergic rhinitis. Allergy 2010; 65: 359,367. Abstract Background:, Treating allergic rhinitis may have a downstream anti-inflammatory effect on the lower airways. We conducted a dose ranging study in asthma and persistent allergic rhinitis to evaluate if intranasal corticosteroids exhibit a sparing effect on the dose of inhaled corticosteroid. Methods:, Twenty five participants were randomized to receive two weeks of 100 ,g/day (Low dose) or 500 ,g/day (High dose) of inhaled fluticasone propionate both with intranasal placebo; or inhaled fluticasone 100 ,g/day with intranasal fluticasone 200 ,g/day (Combined) in a double-blind cross-over fashion. Results:, Low dose fluticasone produced a shift of 1.20 doubling-dilutions (95% CI, 0.63, 1.77); Combined fluticasone, 1.79 doubling-dilutions (95% CI, 0.77, 2.80) and high dose fluticasone, 2.01 doubling-dilutions (95% CI, 1.42, 2.61) in methacholine PC20 from respective baselines. There was a significant difference between high and low doses: 0.82 doubling dilutions (95%CI, 0.12, 1.50) but not between combined and low dose 0.58 doubling dilutions (95% CI, ,0.78, 1.95). Combined treatment alone produced improvements in peak nasal inspiratory flow (P < 0.001), rhinitis quality of life (P = 0.004) and nasal NO (P = 0.01); reduced blood eosinophil count (P = 0.03), and serum eosinophil cationic protein (P = 0.02). All treatments significantly improved tidal NO, FEV1 and asthma quality of life. Conclusions:, High-dose fluticasone was superior to low dose fluticasone for methacholine PC20, demonstrating room for further improvement. Combined treatment was not significantly different from low dose fluticasone and we could not demonstrate a steroid sparing effect on methacholine PC20. Combined treatment alone produced improvements in upper airway outcomes and suppressed systemic inflammation but not adrenal function. [source] Menatetrenone (Vitamin K2) and Bone Quality in the Treatment of Postmenopausal OsteoporosisNUTRITION REVIEWS, Issue 12 2006Jun Iwamoto MD Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment [source] Modulatory effects of curcumin and resveratrol on lung carcinogenesis in micePHYTOTHERAPY RESEARCH, Issue 9 2010Anshoo Malhotra Abstract The aim of the present study is to explore the chemopreventive potential of curcumin and resveratrol during promotional phase of benzo(a)pyrene (BP) induced lung carcinogenesis in mice. The mice were segregated into five groups which included normal control, BP-treated, BP+curcumin-treated, BP+resveratrol-treated and BP+curcumin+resveratrol-treated groups. The BP treatment resulted in a significant increase in the levels of lipid peroxidation (LPO). On the other hand, reduced glutathione (GSH) levels and the activities of superoxide dismutase (SOD) were found to be significantly decreased following BP treatment. Administration of curcumin to BP-treated mice decreased the levels of LPO significantly. Further, treatment of resveratrol to BP-treated mice significantly elevated the activities of SOD. Combined treatment of curcumin and resveratrol, kowever, showed significant improvement in LPO and GSH levels as well as in the activities of SOD. Histo-architectural studies showed well-differentiated signs of lung carcinogenesis following BP administration to mice. Although treatments with resveratrol and curcumin given separately to BP-treated mice showed appreciable improvement in the histo-architecture of the lung, combined treatment resulted in a noticeable improvement in the lung histo-architecture. Copyright © 2009 John Wiley & Sons, Ltd. [source] Latest news and product developmentsPRESCRIBER, Issue 8 2008Article first published online: 12 MAY 200 Glargine preferred to lispro as type 2 add-on Basal insulin glargine (Lantus) and insulin lispro (Humalog) at mealtimes improved glycaemic control equally well in patients with type 2 diabetes poorly controlled by oral agents, but patient satisfaction was greater with basal insulin (Lancet 2008;371:1073-84). The 44-week APOLLO trial, funded by Sanofi Aventis, was a nonblinded randomised comparison of basal and prandial insulin regimens added to oral treatment in 418 patients. It found similar reductions in HbA1C (,1.7 vs ,1.9 per cent respectively). Fasting and nocturnal glucose levels were lower with insulin glargine and postprandial levels were lower with insulin lispro. The basal regimen was associated with fewer hypoglycaemic events (5.2 vs 24 per patient per year), less weight gain (3.01 vs 3.54kg) and greater improvement in patient satisfaction scores. Treating hypertension cuts mortality in over-80s Treating hypertension in the over-80s reduces all-cause mortality by 21 per cent, the HYVET study has shown (N Engl J Med online: 31 March 2008; doi: 10.1056/NEJMoa 0801369). Compared with placebo, treatment with indapamide alone or with perindopril for an average of 1.8 years also reduced the incidence of fatal stroke by 39 per cent, cardiovascular death by 23 per cent and heart failure by 64 per cent. The incidence of stroke was reduced by 30 per cent but this was of borderline statistical significance. Fewer serious adverse events were reported with treatment than with placebo. New work for NICE The DoH has announced the 18th work programme for NICE. Seven public health interventions include preventing skin cancer, smoking by children and excess weight gain during pregnancy. Public health guidance will include the provision of contraceptive services for socially disadvantaged young people. Two new clinical guidelines are sedation in young people and management of fractured neck of femur. New technology appraisals may include eight therapies for cancer, two new monoclonal antibodies for psoriasis and rheumatoid arthritis, an oral retinoid for severe chronic hand eczema and methylnaltrexone for opioid-induced bowel dysfunction. Combinations no better against CV disease Taking ezetimibe and simvastatin (Inegy) does not appear to slow the progression of atherosclerosis more than high-dose simvastatin alone, say researchers from The Netherlands (N Engl J Med 2008;358: 1431-43). In patients with hypercholesterolaemia, there was no difference in regression or progression of atherosclerosis after two years' treatment with simvastatin 80mg per day alone or combined with ezetimibe 10mg per day. Adverse event rates were similar. In patients with vascular disease or high-risk diabetes, there was no difference between the ACE inhibitor ramipril 10mg per day or the ARB telmisartan (Micardis) 80mg per day as monotherapy, or their combination, in the risk of a composite outcome of cardiovascular death, MI, stroke and admission for heart failure (N Engl J Med 2008;358:1547-59). Combined treatment was associated with higher risks of hypotensive symptoms, syncope and renal dysfunction. Twice-daily celecoxib increases CV risk Taking celecoxib (Celebrex) twice daily carries a higher risk of cardiovascular events than the same total dose taken once daily, a metaanalysis suggests (Circulation 2008; doi: 10.1161/ CIRCULATIONAHA.108. 764530). The analysis of six placebo-controlled trials involving a total of 7950 patients taking celecoxib for indications other than rheumatoid arthritis found that the combined risk of cardiovascular death, myocardial infarction, stroke, heart failure or thromboembolic event increased with dose over the range 400-800mg per day. The risk was significantly greater with 200mg twice daily (HR 1.8) than 400mg once daily (HR 1.1). Patients at greatest baseline risk were at disproportionately increased risk from celecoxib. Long-term etanercept effective in AS An open-label study suggests that etanercept (Enbrel) remains effective in the treatment of ankylosing spondylitis in the long term (Ann Rheum Dis 2008;67:346-52). Of 257 patients who completed six months' treatment with etanercept and who entered the nonblinded extension study, 126 completed a total of 168-192 weeks' treatment. The commonest adverse events were injection-site reactions (22 per cent), headache (20 per cent) and diarrhoea (17.5 per cent). The annual rate of serious infections was 0.02 per person. Response and partial remission rates after 192 weeks were similar to those reported after 96 weeks. Metformin reduces risk Metformin reduces the risk of developing diabetes in individuals at increased risk, a meta-analysis suggests (Am J Med 2008;121:149-57.e2). The study included 31 mostly small, randomised, controlled trials involving a total of 4570 participants and lasting at least eight weeks (8267 patient-years of treatment). Metformin was associated with reductions in body mass (,5.3 per cent), fasting glucose (,4.5 per cent) and insulin resistance (,22.6 per cent); lipid profiles also improved. The odds of developing diabetes were reduced by 40 per cent,an absolute risk reduction of 6 per cent over 1.8 years. MHRA clarifies cough and colds advice Press reports mistakenly suggested that the MHRA had banned some cough and cold remedies when it issued new guidance on treating young children, the MHRA says. The Agency's advice followed a review of over-thecounter cough and cold medicines for children by the Commission on Human Medicines. Children under two are at increased risk of adverse reactions and should no longer be treated with products containing antihistamine (chlorphenamine, brompheniramine, diphenhydramine), antitussives (dextromethorphan, pholcodine), expectorants (guaifenesin, ipecacuanha) and decongestants (phenylephrine, pseudoephedrine, ephedrine, oxymetazoline and xylometazoline). The MHRA said these products, which are classified as general sale medicines, should be removed from open shelves until available in new packaging that complies with the advice. They may still be supplied by a pharmacist for the treatment of older children. Coughs and colds should be treated with paracetamol or ibuprofen for fever, a simple glycerol, honey or lemon syrup for cough, and vapour rubs and inhalant decongestants for stuffy nose. Saline drops can be used to thin and clear nasal secretions in young babies. Parents are being urged not to use more than one product at a time to avoid inadvertently administering the same constituent drug twice. Perindopril brand switch Servier Laboratories is replacing its current formulations of perindopril (Coversyl, Coversyl Plus) with a new product that is not bioequivalent. The current Coversyl brand contains perindopril erbumine (also known as tert -butylamine). The new formulation contains perindopril arginine; it will be distinguished by new brand names (Coversyl Arginine, Coversyl Arginine Plus) and new packaging. Coversyl 2, 4 and 8mg tablets are equivalent to Coversyl Arginine 2.5, 5 and 10mg. Servier says the change is part of the simplification and harmonisation of global manufacturing; the arginine salt is already used in other countries and offers greater stability and a longer shelf-life. Both Coversyl and Coversyl Arginine will be in the supply chain for the next few weeks. Generic perindopril will continue to be the erbumine salt and prescriptions for generic perindopril are not affected. New from NICE Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. Clinical Guidance No. 63, March 2008 This clinical guideline focuses on additional aspects of care for women with gestational diabetes (88 per cent of cases) or pre-existing diabetes (of which about 40 per cent is type 2 diabetes) and their babies. To date, insulin aspart (NovoRapid) is the only drug in the guideline specifically licensed for use in pregnancy and NICE advises obtaining informed consent to implement its recommendations for using other insulins and oral hypoglycaemic agents. As with other guidelines, NICE begins by stressing the importance of patient-centred care and involving women in decisions about their treatment. The guideline is divided into six sections, dealing with consecutive periods of pregnancy. Preconceptual planning should include empowering women to help them reduce risks, optimising glycaemic control (after retinal assessment) and increasing monitoring intensity, and providing information about the effects of pregnancy on diabetes. Metformin may be recommended as an adjunct or alternative to insulin, but other oral hypoglycaemic agents should be replaced with insulin, although glibenclamide is an option during pregnancy. Isophane insulin is the preferred long-acting insulin; lispro (Humalog) and aspart are considered safe to use. ACE inhibitors and angiotensin-II receptor blockers should be replaced with other antihypertensive agents and statins should be discontinued. Recommendations for screening and treatment of gestational diabetes build on previous guidance (CG62). Drug treatment will be needed by 10-20 per cent , this includes insulin (soluble, aspart or lispro) and/or metformin or glibenclamide, tailored to individual need. Antenatal care includes optimising glycaemic control. Insulin lispro or aspart should be considered in preference to soluble insulin. If glycaemic control cannot be achieved with insulin injections, an insulin pump may be indicated. The guideline includes a timetable for appointments and the care that should offered after each interval. Recommendations for intrapartum care, which supplement those in CG55, include frequent monitoring of blood glucose. Neonatal care includes recommendations for monitoring and screening the infant and the management of hypoglycaemia. Postnatal care (supplementing CG37) involves adjusting maternal treatment to avoid hypoglycaemia and recommendations for returning to community care. Metformin and glibenclamide are the only oral agents suitable for breastfeeding women. Women with gestational diabetes need advice about glycaemic control and planning for future pregnancies. Lifestyle advice and measurement of annual fasting plasma glucose should be offered. Inhaled corticosteroids for the treatment of chronic asthma in adults and in children aged 12 years and over. Technology Appraisal No. 138, March 2008 The latest technology appraisal of asthma treatments covers inhaled steroids for adults and children over 12 with chronic asthma. It makes only two recommendations. First, the cheapest appropriate option is recommended. Second, when a steroid and a long-acting beta2-agonist are indicated, the decision to prescribe a combined inhaler or separate devices should take into account therapeutic need and likely adherence. Combined inhalers are currently less expensive than separate devices, though they may not remain so. When a combined inhaler is chosen it should be the cheapest. NICE concludes that, at equivalent doses, there is little difference in the effectiveness or adverse event profile of the available steroids or the fixed-dose combinations. According to specialist advice, choosing the best device for an individual remains the overriding concern. Continuous positive airway pressure for the treatment of obstructive sleep apnoea/hypopnoea syndrome. Technology Appraisal No. 139, March 2008 NICE recommends continuous positive airway pressure (CPAP) for adults with moderate or severe obstructive sleep apnoea, and for those with a milder disorder if quality of life and functioning are impaired and alternative strategies such as lifestyle change have failed. Diagnosis and treatment is the responsibility of a specialist team. A CPAP device costs £250-£550 and lasts for seven years. Copyright © 2008 Wiley Interface Ltd [source] Combined radiation therapy and dendritic cell vaccine for treating solid tumors with liver micro-metastasisTHE JOURNAL OF GENE MEDICINE, Issue 4 2005Zhuang Chen Abstract Background Tumor metastasis and relapse are major obstacles in combating human malignant diseases. Neither radiotherapy alone nor injection of dendritic cells (DCs) can successfully overcome this problem. Radiation induces tumor cell apoptosis and necrosis, resulting in the release of tumor antigen and danger signals, which are favorable for DC capturing antigens and maturation. Hence, the strategy of combined irradiation and DC vaccine may be a novel approach for treating human malignancies and early metastasis. Methods To develop an effective combined therapeutic approach, we established a novel concomitant local tumor and liver metastases model through subcutaneous (s.c.) and intravenous (i.v.) injection. We selected the optimal time for DC injection after irradiation and investigated the antitumor effect of combining irradiation with DC intratumoral injection and the related mechanism. Results Combined treatment with radiotherapy and DC vaccine could induce a potent antitumor immune response, resulting in a significant decrease in the rate of local tumor relapse and the numbers of liver metastases. The related mechanisms for this strong antitumor immunity of this combined therapy might be associated with the production of apoptotic and necrotic tumor antigens and heat shock proteins after irradiation, phagocytosis, migration and maturation of DCs, and induction of more efficient tumor-specific cytotoxic T lymphocyte activity through a cross-presentation pathway. Conclusions Co-administration of local irradiation and intratumoral DC injection may be a promising strategy for treating radiosensitive tumors and eliminating metastasis in the clinic. Copyright © 2004 John Wiley & Sons, Ltd. [source] Islet Transplantation for Brittle Type 1 Diabetes: The UIC ProtocolAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008A. Gangemi This prospective phase 1/2 trial investigated the safety and reproducibility of allogeneic islet transplantation (Tx) in type I diabetic (T1DM) patients and tested a strategy to achieve insulin-independence with lower islet mass. Ten C-peptide negative T1DM subjects with hypoglycemic unawareness received 1,3 intraportal allogeneic islet Tx and were followed for 15 months. Four subjects (Group 1) received the Edmonton immunosuppression regimen (daclizumab, sirolimus, tacrolimus). Six subjects (Group 2) received the University of Illinois protocol (etanercept, exenatide and the Edmonton regimen). All subjects became insulin- independent. Group 1 received a mean total number of islets (EIN) of 1460 080 ± 418 330 in 2 (n = 2) or 3 (n = 2) Tx, whereas Group 2 became insulin- independent after 1 Tx (537 495 ± 190 968 EIN, p = 0.028). All Group 1 subjects remained insulin free through the follow-up. Two Group 2 subjects resumed insulin: one after immunosuppression reduction during an infectious complication, the other with exenatide intolerance. HbA1c reached normal range in both groups (6.5 ± 0.6 at baseline to 5.6 ± 0.5 after 2,3 Tx in Group 1 vs. 7.8 ± 1.1 to 5.8 ± 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets. [source] Combined treatment with vitamin E and colchicine in the early stages of Peyronie's diseaseBJU INTERNATIONAL, Issue 6 2003R.M. Prieto Castro Objective To assess the effectiveness of the combination of colchicine and vitamin E (which has anti-fibrotic, anti-mitotic and anti-inflammatory effects) in modifying the early stages of Peyronie's disease, by evaluating pain relief, correction of deformities and plaque size. Patients and methods In all, 45 patients were divided into two groups and treated from January 1998 to November 2001. Their mean (range) age was 53.4 (40,62) years, the time from onset of the disease < 6 months and they had penile deformity of < 30°; no patient had erectile dysfunction. Twenty-two patients were given ibuprofen 400 mg/day for 6 months, whilst 23 received a combination of vitamin E 600 mg/day plus colchicine 1 mg every 12 h. Pain, plaque size and penile deformity were assessed at 6 months. Results There were no statistically significant differences between the groups at baseline in age, time from onset of the disease until the initial evaluation or plaque size. Although the proportion of patients reporting pain relief was higher amongst those receiving colchicine plus vitamin E (91% vs 68%) this was not significantly different, but differences in plaque size and penile curvature were significant. Conclusions The use of colchicine plus vitamin E during the early stages of Peyronie's disease (time from onset < 6 months) in patients with penile curvature of < 30° and no erectile dysfunction is an effective and well-tolerated way to stabilize the disease. A more extensive study is needed, comparing these results with other oral therapies. [source] Effects of combined inhibition of the Na+,H+ exchanger and angiotensin-converting enzyme in rats with congestive heart failure after myocardial infarctionBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2005Hartmut Ruetten We investigated the single vs the combined long-term inhibition of Na+,H+ exchanger-1 (NHE-1) and ACE in rats with congestive heart failure induced by myocardial infarction (MI). Rats with MI were randomized to receive either placebo, cariporide (3000 p.p.m. via chow), ramipril (1 mg kg,1 day,1via drinking water) or their combination for 18 weeks starting on day 3 after surgery. Cardiac morphology and function was assessed by echocardiography and by means of a 2.0 F conductance catheter to determine left ventricular (LV) pressure volume relationships. MI for 18 weeks resulted in an increase in LV end-diastolic diameter (LVDed) in the placebo-treated group when compared to sham (placebo: 1.1±0.04 cm; sham: 0.86±0.01; P<0.05). Combined inhibition of NHE-1 and ACE, but not the monotherapies, significantly reduced LVDed (1.02±0.02 cm). Preload recruitable stroke work (PRSW), dp/dtmax (parameter of systolic function) and end-diastolic pressure volume relationship (EDPVR, diastolic function) were significantly impaired in placebo-treated MI group (PRSW: 39±7 mmHg; dp/dtmax: 5185±363 mmHg s,1; EDPVR: 0.042±0.001 mmHg ,l,1; all P<0.05). Cariporide treatment significantly improved PRSW (64±7 mmHg), dp/dtmax (8077±525 mmHg s,1) and EDPVR (0.026±0.014 mmHg ,l,1), and reduced cardiac hypertrophy in rats with MI. Combined inhibition of NHE-1 and ACE had even a more pronounced effect on PRSW (72±5 mmHg) and EDPVR (0.026±0.014 mmHg ,l,1), as well as cardiac hypertrophy that, however, did not reach statistical significance compared to cariporide treatment alone. The NHE-1 inhibitor cariporide significantly improved LV remodeling and function in rats with congestive heart failure induced by MI. The effect of cariporide was comparable or tended to be stronger (e.g. systolic function) compared to ramipril. Combined treatment with cariporide and ramipril tended to be more effective on LV remodeling in rats with heart failure than the single treatments. Thus, inhibition of the NHE-1 may be a promising novel therapeutic approach for the treatment of congestive heart failure. British Journal of Pharmacology (2005) 146, 723,731. doi:10.1038/sj.bjp.0706381 [source] Treatment of oesophageal anastomotic leaks by temporary stenting with self-expanding plastic stentsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2009Y. Y. Dai Background: Oesophageal anastomotic leakage is associated with considerable morbidity and mortality. The aim of the present study was to assess the feasibility of using temporary self-expanding plastic stents to treat postoperative oesophageal leaks. Methods: Patients with anastomotic leakage after abdominothoracic oesophagectomy treated by endoscopic insertion of self-expanding plastic stents between 2001 and 2007 were studied. Clinical outcomes were analysed, including healing of the leak, morbidity and mortality. Results: Stents were inserted successfully in all 22 patients without procedure-related complications. Ten patients also required computed tomography-guided drainage because surgical drains had been removed. Non-ventilated patients received oral nutrition a mean of 4 days after stent placement. Combined treatment with stenting and drainage resulted in resolution of the leak in 21 of 22 patients. The mean healing time (time to stent removal) was 23 days. Stent migration occurred in five of 22 patients, but endoscopic reintervention with placement of a new stent was successful in all patients. Repeat thoracotomy with intraoperative stent placement was necessary in one patient with an oesophagocolonic anastomosis. One patient died in hospital. Conclusion: In combination with effective drainage, self-expanding plastic stents are an option for the treatment of oesophageal anastomotic leaks, and may reduce leak-related morbidity and mortality. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Application of a vagal nerve stimulator in an epilepsy patient with cardiac pacemaker after post-ictal cardiac arrestACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009R. Cáceres In this case report we present a patient with temporal lobe epilepsy (TLE) showing partial complex seizures and secondary generalization, and treated with several antiepileptic drugs. After two consecutive seizures she had an episode of cardiac arrest followed by AV-block III which led to the implantation of a cardiac pacemaker. She subsequently received a vagal nerve stimulator because of poor response to epilepsy treatment. Combined treatment with two different electromagnetic stimulators raises the question of safety during surgery which is discussed. [source] Combined treatment with pegylated interferon,,-2a and dacarbazine in patients with advanced metastatic melanomaCANCER, Issue 6 2008A phase 2 study Abstract BACKGROUND. Dacarbazine (DTIC) and pegylated interferon (IFN),,-2a have both demonstrated some efficacy as single agents in metastatic melanoma. To the authors' knowledge, the current study is the first to test a combination of these 2 agents in a phase 2 trial. METHODS. Twenty,eight patients with stage IV melanoma without brain metastases were treated with DTIC (at a dose of 850 mg/m2 every 3 weeks) combined with weekly pegylated IFN,,-2a at a dose of 180 ,g. The study was initiated to evaluate the efficacy and tolerability of the combination. The primary study endpoint was objective response. RESULTS. Twenty,five patients were evaluable for response. Two patients (8.0%) achieved a complete response that continued for >480 days and 746 days, respectively. Four patients (16.0%) demonstrated a partial response, and another patient experienced stable disease. Six of 7 nonprogressive patients had either not received treatment or had not developed disease progression during adjuvant IFN treatment for stage II/III disease. The median duration of response was 236 days, the median progression-free survival was 56 days, and the overall survival time was 403 days. Few grade 3 toxicities and only 1 grade 4 toxicity were observed (according to National Cancer Institute Common Toxicity Criteria). CONCLUSIONS. The combination of DTIC and pegylated IFN,,-2a was found to be well tolerated in patients with metastatic melanoma. The response rate of 24%, including 2 long-lasting complete responses, is encouraging, but must be confirmed in larger trials. Cancer 2008. © 2008 American Cancer Society. [source] Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancersCANCER SCIENCE, Issue 6 2010Tatsuhiro Ohgami MDM2 is a direct negative regulator of p53. The p53-independent mdm2-P1 and p53-dependent mdm2-P2 promoters have been recently shown to harbor Sp1 binding sites. Mithramycin, an inhibitor of Sp1 DNA binding, has been used clinically to treat hypercalcemia and some types of neoplastic disorders. In this study, we investigated the mechanisms behind the anticancer effect of mithramycin. In gynecologic cancer cells expressing wild-type p53, mithramycin stabilized p53 and increased the expression of the p53 downstream target genes PUMA and p21, arrested the cell cycle, and induced apoptosis. This activation of the p53 signaling pathway was a specific effect of MTH at concentrations <50 nm. Mithramycin temporally decreased transcription of both the mdm2-P1 and -P2 promoters. This was followed by a subsequent increase of mdm2-P2 promoter activity by activated p53. Up-regulated MDM2 was in its active form, and consequently attenuated p53 activity. Although mithramycin activated p53 and suppressed the growth of human gynecologic cancer cell xenografts in mice, this was accompanied with a secondary up-regulation of MDM2. Combined treatment with mithramycin and nutlin-3, a drug that inhibits MDM2,p53 interaction, overcame a secondary up-regulation of MDM2 and synergistically inhibited cancer cell growth by inducing apoptosis through activation of the p53 signaling pathway. These observations provide a better understanding of the mechanisms of mithramycin activity, and suggest a potential role for combining mithramycin and nutlin-3 as a chemotherapeutic treatment for gynecologic cancers. (Cancer Sci 2010; 101: 1387,1395) [source] Therapeutic strategy using phenotypic modulation of cancer cells by differentiation-inducing agentsCANCER SCIENCE, Issue 11 2007Yoshio Honma A low concentration of differentiation inducers greatly enhances the in vitro and in vivo antiproliferative effects of interferon (IFN), in several human cancer cells. Among the differentiation inducers tested, the sensitivity of cancer cells to IFN, was most strongly affected by cotylenin A. Cotylenin A, which is a novel fusicoccane diterpene glycoside with a complex sugar moiety, affected the differentiation of leukemia cells that were freshly isolated from acute myelogenous leukemia patients in primary culture. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were early genes induced by the combination of cotylenin A and IFN, in carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN, cooperatively induced apoptosis through the TRAIL signaling system. Combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells. In an analysis of various cancer cell lines, ovarian cancer cells were highly sensitive to combined treatment with cotylenin A and IFN, in terms of the inhibition of cell growth. This treatment was also effective toward ovarian cancer cells that were refractory to cisplatin, and significantly inhibited the growth of ovarian cancer cells as xenografts without apparent adverse effects. Ovarian cancer cells from patients were also sensitive to the combined treatment in primary cultures. Combined treatment with cotylenin A and IFN, may have therapeutic value in treating human cancers including ovarian cancer. (Cancer Sci 2007; 98: 1643,1651) [source] Thrombosis of an extracardiac fontan tunnel: Combined treatment of thrombolysis and stenting,CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 6 2009Ralf Rauch MD Abstract Obstruction of the so-called Fontan tunnel represents a life-threatening complication and requires immediate intervention. We describe the successful use of prolonged thrombolysis with rt-PA, allowing stent placement in an extracardiac tunnel in a 7-year-old boy. © 2009 Wiley-Liss, Inc. [source] Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative Stress in mice treated with carbon tetrachloridePHYTOTHERAPY RESEARCH, Issue 7 2006Mira Popovi Abstract Extracts of celery leaves and roots in ether, chloroform, ethyl acetate, n -butanol and water were evaporated to dryness and dissolved in 50% ethanol to make 10% (w[sol ]v) solutions. The potential protective action of the extracts was assessed by the corresponding in vitro and in vivo tests. In the in vitro experiments crude methanol extracts were tested as potential scavengers of free OH, and DPPH, radicals, as well as inhibitors of liposomal peroxidation (LPx). Analogous experiments were also carried out with the extracts of celery root, for comparison. The results obtained show that both the extracts of root and leaves are good scavengers of OH, and DPPH, radicals and reduce LPx intensity in liposomes, which points to their protective (antioxidant) activity. In vivo experiments were concerned with antioxidant systems (activities of GSHPx, GSHR, Px, CAT, XOD, GSH content and intensity of LPx) in liver homogenate and blood of mice after their treatment with extracts of celery leaves, or in combination with CCl4. On the basis of the results obtained it can be concluded that the examined extracts showed a certain protective effect. Of all the extracts the n -butanol extract showed the highest protective effect. Combined treatments with CCl4 and extracts showed both positive and negative synergism , inducing or suppressing the impact of CCl4 alone. The differences observed in the action of particular extracts are probably due to the different contents of flavonoids and some other antioxidant compounds. Copyright © 2006 John Wiley & Sons, Ltd. [source] The Myth of the Superiority of Concurrent Combined Treatments for Anxiety DisordersCLINICAL PSYCHOLOGY: SCIENCE AND PRACTICE, Issue 2 2010Kristin E. Pontoski [Clin Psychol Sci Prac 17: 107,111, 2010] The treatment of anxiety disorders with combined cognitive-behavioral therapy (CBT) and pharmacological treatments has been an ongoing topic of discussion. Combined treatments have failed to demonstrate additive benefits despite their continued use in practice. Otto, McHugh, and Kantak (2010) suggest that concurrent use of medication and CBT affects the acute release of cortisol during the extinction phase of exposure therapy and, in turn, interferes with memory consolidation. This commentary expands on some of the psychological aspects of combined treatments for anxiety disorders to consider along with this new biochemical perspective. [source] Combined treatment of achalasia , botulinum toxin injection followed by pneumatic dilatation: long-term resultsDISEASES OF THE ESOPHAGUS, Issue 2 2010R. Kroupa SUMMARY Injection of botulinum toxin (BT) and pneumatic dilatation are available methods in nonsurgical treatment of achalasia. Authors anticipate beneficial effect of prior BT injection on the success of pneumatic dilatation and duration of its effect. There are no long-term data available to assess efficacy of combined treatment. From 1998 to 2007, 51 consecutive patients (20 men and 31 women, age 24,83) with achalasia were included and prospectively followed up. Each patient received injection of 200 IU of BT into the lower esophageal sphincter (LES) during endoscopy and 8 days later pneumatic dilatation (PD) under X-ray control was performed. The follow-up was established every 3 months first year and then annually. The efficacy was evaluated by a questionnaire concerning patient's symptoms and manometry. Results were compared with 40 historical controls (16 men and 24 women, age 26,80) treated by PD alone using the same method and follow-up. Fifty-one patients underwent combined treatment. Four patients failed in follow-up and were not included for analysis. The mean duration of follow-up was 48 months with range 12,96 months. Thirty-four of forty-seven (72%) patients were satisfied with results with none or very rare and mild troubles at the time of the last visit. Forty-one patients were followed up more than 2 years. Effect of therapy lasted in 75% (31/41) of them. In 17 patients, more than 5 years after treatment, effect lasted in 12 (70%). Mean tonus of LES before therapy was 29 mm Hg (10,80), 3 months after therapy decreased to 14 mmHg (5,26). The cumulative 5 years remission rate (±95% CI) in combined treated patients 69% ± 8% was higher than in controls 50% ± 9%; however it, was not statistically significant (P= 0.07). In control group 1, case of perforation (2.5%) occurred. Eight patients (17%) with relapse of dysphagia were referred to laparoscopic Heller myotomy with no surgical complication. The main adverse effect was heartburn that appeared in 17 patients (36%). Initial injection of BT followed by PD seems to be effective for long-term results with fewer complications. But the combined therapy is not significantly superior to PD alone. [source] Barrett's esophagus: combined treatment using argon plasma coagulation and laparoscopic antireflux surgeryDISEASES OF THE ESOPHAGUS, Issue 4 2003M. Pagani SUMMARY, The treatment of Barrett's esophagus is still controversial. Actually, the only method to prevent the development to cancer is endoscopic surveillance, which ensures good results in terms of long-term survival. An ideal treatment capable of destroying columnar metaplasia, followed by squamous epithelium regeneration could potentially result in a decrease of the incidence of adenocarcinoma. Recently most ablative techniques were used, such as photodynamic therapy, ablation therapy with Nd-YAG laser or argon plasma coagulation and endoscopic mucosal resection. We started a prospective study in January 1998, enrolling 94 patients affected by Barrett's esophagus and candidates for antireflux repair in order to assess the effectiveness and the results of endoscopic coagulation with argon plasma combined with surgery in the treatment of uncomplicated Barrett's esophagus. All patients underwent endoscopic treatment with argon plasma; we observed complete response in 68 patients (72.34%), 27 of them (39.7%) underwent antireflux surgery and the other 41 continued medical therapy. Post-operatively 19 patients (70%) underwent regular surveillance endoscopies and in two cases metaplasia recurred. The final objective of these combined treatments should be the complete eradication of metaplastic mucosa. Our experience was that argon plasma coagulation combined with antireflux surgery or proton pump inhibitor therapy gave satisfactory results, even if follow-up is too short to evaluate the potential evolution of metaplasia to cancer. For this reason, we recommend that this technique should be done only in specialized centres and that these patients continue their endoscopic surveillance program. [source] | ||||||||||||||||||||||||||||||||||||||||