A General Model for Estimating and Correcting the Effects of Nonindependence in Meta-Analysis.

ERIC Educational Resources Information Center

Strube, Michael J.

A general model is described which can be used to represent the four common types of meta-analysis: (1) estimation of effect size by combining study outcomes; (2) estimation of effect size by contrasting study outcomes; (3) estimation of statistical significance by combining study outcomes; and (4) estimation of statistical significance by…

Cytotoxic Effects of the Therapeutic Radionuclide Rhenium-188 Combined with Taxanes in Human Prostate Carcinoma Cell Lines.

PubMed

Lange, Rogier; ter Heine, Rob; van Wieringen, Wessel N; Tromp, Adrienne M; Paap, Mayke; Bloemendal, Haiko J; de Klerk, John M H; Hendrikse, N Harry; Geldof, Albert A

2017-02-01

Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188 Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188 Re in prostate carcinoma cell lines. The cytotoxic effects of single and combined treatment with taxanes and 188 Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188 Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. This proof-of-mechanism study exploring radiosensitization by combining 188 Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188 Re-HEDP.

Addition of citral controls ROS and reduces toxicity in 5-fluorouracil treated Schizosaccharomyces pombe cells.

PubMed

Patel, Pinaki B; Thakkar, Vasudev R

2015-03-01

In systemic therapy, chemotherapeutic drugs, often, cause considerable side effects; and combination of natural compounds lessen the extent of such effects. In the present study, combined effect of citral and 5-fluorouracil was studied in Schizosaccharomyces pombe cells. The antagonistic combination index found was at 0.01 and 0.025 mM of citral with 40 μg or higher concentration of 5-fluorouracil. The combined treatment was so effective that higher number of cells underwent apoptosis compared to individual treatment of 5-fluorouracil. Citral controlled ROS levels and increased survival of normal cells. Several differentially expressed proteins observed in the citral treatment could further help understanding its mechanism of action.

A study of the effects of physical dermabrasion combined with chemical peeling in porcine skin.

PubMed

Kang, Boo Kyoung; Choi, Jeong Hwee; Jeong, Ki Heon; Park, Jong Min; Suh, Dong Hye; Lee, Sang Jun; Shin, Min Kyung

2015-02-01

Many comparative studies of chemical peeling and dermabrasion have been reported. However, rare basic scientific data about the immediate effects after combined treatment with chemical peeling and dermabrasion have been confirmed. The aim of this study is to evaluate the effect of the application of physical abrasion in combination with chemical peels. Three pigs were treated with physical abrasion using a water jet device in combination with an α-hydroxy acid solution, and the skin samples of the control received chemical peeling solution alone. The levels of growth factors and neuropeptides were measured with a multiplex immunoassay. Skin treated with physical dermabrasion combined with chemical peeling showed prominent detachment and swelling of the stratum corneum (SC), and fluid collection in the hair follicles. The mean cell count of CD34 positive fibroblasts and mast cells, levels of epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, and neurotensin, were significantly increased in the tissue treated with physical abrasion combined with a chemical peeling agent, compared to the skin in the control. We concluded that physical dermabrasion combined with chemical peeling can be more effective than chemical peeling alone, for the approach through transfollicular routes.

Marijuana, alcohol and actual driving performance

DOT National Transportation Integrated Search

1999-07-01

The purpose of this study was to empirically determine the separate and combined effects of Delta-9-tetrahydrocannabinol (THC) and alcohol on actual driving performance. This was the first study ever in which the drugs' combined effects were measured...

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation.

PubMed

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong; Ding, Xianting

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved.

Identification of Centella asiatica's Effective Ingredients for Inducing the Neuronal Differentiation

PubMed Central

Jiang, Hui; Zheng, Guoshuai; Lv, Junwei; Chen, Heyu; Lin, Jinjin; Li, Yiyang; Fan, Guorong

2016-01-01

Centella asiatica, commonly known as Gotu kola, has been widely used as a traditional herb for decades. Yet, the study on which compounds or compound combinations actually lead to its brain benefits remains scarce. To study the neuroprotection effects of Centella asiatica, neuronal differentiation of PC12 cells was applied. In our pilot study, we isolated 45 Centella asiatica fractions and tested their abilities for inducing neuronal differentiation on PC12 cells. The most effective fraction showed robust induction in neurite outgrowth and neurofilament expression. LC-MS fingerprint analysis of this fraction revealed asiatic acid and madecassic acid as the dominant components. A further investigation on the pure combination of these two compounds indicated that the combination of these two compounds extensively promoted nerve differentiation in vitro. Application of PD98059, a protein MEK inhibitor, attenuated combination-induced neurofilament expression, indicating the combination-induced nerve differentiation through activation of MEK signaling pathway. Our results support the use of combination of asiatic acid and madecassic acid as an effective mean to intervene neurodegenerative diseases in which neurotrophin deficiency is involved. PMID:27446228

Ethnic differences in the effectiveness of cognitive behavioral therapy combined with medication: Comparing Asian American and white psychiatric patients.

PubMed

Tang, Jennifer Y; Li, Chieh; Rodgers, Rachel F; Ballou, Mary

2016-12-01

Several meta-analyses have demonstrated the effectiveness of treatment utilizing cognitive behavioral therapy (CBT) combined with medication. There is, however, a paucity of research comparing the effectiveness of this combined treatment with psychiatric patients from different ethnic backgrounds. This study is the first of its kind to compare the effectiveness of CBT combined with medication for Asian American and White patients' psychiatric symptom severity levels of depression, anxiety, psychological well-being, and quality of life. The study examined the effects of CBT combined with medication for 43 Asian American and 43 White Non-Hispanic patients at an acute psychiatric partial hospital. A 2×2 between-within repeated measures analysis of variance was used. Results indicated significant improvement after treatment in all symptom categories assessed for the Asian American and White patients. The findings displayed trends over the course of treatment toward a greater decrease in anxiety symptoms among Asian patients but a larger increase in functioning level among White patients. In conclusion, the findings from this study provide preliminary cross-cultural support for CBT combined with medication as a treatment in partial hospital settings and suggest that the effectiveness of such treatments is similar across cultural groups. Copyright © 2016. Published by Elsevier B.V.

Cravings as a mediator and moderator of drinking outcomes in the COMBINE study.

PubMed

Subbaraman, Meenakshi Sabina; Lendle, Samuel; van der Laan, Mark; Kaskutas, Lee Ann; Ahern, Jennifer

2013-10-01

Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) study examined whether combining medications with a behavioral intervention would improve outcomes over monotherapies. Unexpectedly, the combination did not offer any advantage over either treatment alone. This study aimed to explain the lack of incremental benefit offered by the combination over either monotherapy by assessing the role of cravings as a treatment mediator and moderator. Secondary mediation and moderation analyses of COMBINE study data. Eleven United States academic sites. A total of 863 patients randomized to one of four treatment groups: naltrexone (100 mg/day; n = 209), the combined behavioral intervention (CBI, n = 236), naltrexone and CBI combined (n = 213) and placebo naltrexone (n = 205). Percentage of days abstinent (PDA) measured between 13 and 16 weeks post-baseline. Cravings, the potential mediator/moderator, were measured at baseline, weeks 4 and 12 using the Obsessive-Compulsive Drinking Scale. Compared with placebo, naltrexone, CBI and the combination all increased PDA by an additional 6-10 percentage points for those with high cravings (P < 0.05 for all three treatment groups). None had significant effects on PDA for those with low cravings. The effects of all three treatments were mediated at least partially by cravings; craving reduction explained 48-53% of treatment effects (P < 0.05 for all three treatment groups). Furthermore, naltrexone appeared to reduce cravings at 4 weeks, while CBI did not reduce cravings until 12 weeks. The Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) naltrexone + CBI combination may not be more beneficial than either monotherapy because craving reduction is a common mechanism of both. © 2013 Society for the Study of Addiction.

Pharmacological aspects of the combined use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and gamma-hydroxybutyric acid (GHB): a review of the literature.

PubMed

Uys, Joachim D K; Niesink, Raymond J M

2005-07-01

Epidemiological studies show that the use of club drugs is on the rise. Furthermore, the last few decades have seen a rise in patterns of polydrug use. One of the combinations frequently used is ecstasy (MDMA) with gammahydroxybutyrate (GHB). For effective prevention it is important to be aware of this phenomenon and of the pharmacology of these drugs. The effects of the combination extend to different neurotransmitter systems, including serotonin, dopamine and noradrenaline. Studies investigating the effects of combinations of psychoactive substances are limited. In this review we describe the subjective effects of the MDMA/GHB combination. Furthermore, we review the individual actions of MDMA on serotonin, dopamine and noradrenaline systems. In addition, actions of GHB on these systems are discussed as a possible pharmacological basis for the interaction of both drugs. It is postulated that GHB attenuates the unpleasant or dysphoric effects of MDMA by its effect on the central dopaminergic system.

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

PubMed

Mita, Sachiko; Chitnis, Shripad D; Kulmatycki, Kenneth; Salunke, Atish; He, Yan-Ling; Zhou, Wei; Suzuki, Hikoe

2016-04-01

To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria.

PubMed

Lee, Wee Xian; Basri, Dayang Fredalina; Ghazali, Ahmad Rohi

2017-03-17

The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5) against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923 , Escherichia coli O157 and Pseudomonas aeruginosa 15442 . However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

In vitro cytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin.

PubMed

Timocin, Taygun; Husunet, Mehmet Tahir; Valipour, Ebrahim; Norizadeh Tazehkand, Mostafa; Celik, Rima; Topaktas, Mehmet; Ila, Hasan B

2017-07-01

Flurbiprofen (FLB) (anti-inflammatory and analgesic drug) and roxithromycin (RXM) (antibiotic) were widely used in world wide. This study deals with investigation of genotoxicity, cytotoxicity, and oxidative stress effects of a particular combination of these drugs in human cultured lymphocytes. Also, DNA damaging-protective effects of combination of these drugs were analyzed on plasmid DNA. Human lymphocytes were treated with different concentrations (FLB + RXM; 10 μg/mL + 25 μg/mL, 15 μg/mL + 50 μg/mL, and 20 μg/mL + 100 μg/mL) of the drugs following by study of their genotoxic and cytotoxic effects by analysis of cytokinesis-block micronucleus test and nuclear division index, respectively. The effect of the combination in aspect of anti-oxidative and DNA damaging activity was evaluated on Pet-22b plasmid. According to our results, the combination of FLB and RXM did not show a notable genotoxic effect on cells. Although each of the substances had been shown as a cytotoxic agent by previous researchers, in this research, the combination of these drugs did not exhibit any adverse effect on cell division. FLB had DNA protection effect against H 2 O 2 while in combination with RXM had not the same effect on the plasmid.

Drought Stress Predominantly Endures Arabidopsis thaliana to Pseudomonas syringae Infection

PubMed Central

Gupta, Aarti; Dixit, Sandeep K.; Senthil-Kumar, Muthappa

2016-01-01

Plant responses to a combination of drought and bacterial pathogen infection, an agronomically important and altogether a new stress, are not well-studied. While occurring concurrently, these two stresses can lead to synergistic or antagonistic effects on plants due to stress-interaction. It is reported that plant responses to the stress combinations consist of both strategies, unique to combined stress and those shared between combined and individual stresses. However, the combined stress response mechanisms governing stress interaction and net impact are largely unknown. In order to study these adaptive strategies, an accurate and convenient methodology is lacking even in model plants like Arabidopsis thaliana. The gradual nature of drought stress imposition protocol poses a hindrance in simultaneously applying pathogen infection under laboratory conditions to achieve combined stress. In present study we aimed to establish systematic combined stress protocol and to study physiological responses of the plants to various degrees of combined stress. Here, we have comprehensively studied the impact of combined drought and Pseudomonas syringae pv. tomato DC3000 infection on A. thaliana. Further, by employing different permutations of drought and pathogen stress intensities, an attempt was made to dissect the contribution of each individual stress effects during their concurrence. We hereby present two main aspects of combined stress viz., stress interaction and net impact of the stress on plants. Mainly, this study established a systematic protocol to assess the impact of combined drought and bacterial pathogen stress. It was observed that as a result of net impact, some physiological responses under combined stress are tailored when compared to the plants exposed to individual stresses. We also infer that plant responses under combined stress in this study are predominantly influenced by the drought stress. Our results show that pathogen multiplication was reduced by drought stress in combined stressed plants. Combined stressed plants also displayed reduced ROS generation and declined cell death which could be attributed to activation of effective basal defense responses. We hypothesize a model on ABA mediated gene regulation to partly explain the possible mechanistic basis for reduced in planta bacterial numbers under combined stress over individual pathogen stress. PMID:27375661

The effects of combined supplementary cementitious materials on physical properties of Kansas concrete pavements.

DOT National Transportation Integrated Search

2013-12-01

This study evaluated the effects of combining varying proportions of slag cement and Class C fly ash : with Type I/II cement in concrete pavement. Three different ternary cementitious material combinations : containing slag cement and Class C fly ash...

The effect of alcohol treatment on social costs of alcohol dependence: results from the COMBINE study.

PubMed

Zarkin, Gary A; Bray, Jeremy W; Aldridge, Arnie; Mills, Michael; Cisler, Ron A; Couper, David; McKay, James R; O'Malley, Stephanie

2010-05-01

The COMBINE (combined pharmacotherapies and behavioral intervention) clinical trial recently evaluated the efficacy of pharmacotherapies, behavioral therapies, and their combinations for the treatment of alcohol dependence. Previously, the cost and cost-effectiveness of COMBINE have been studied. Policy makers, patients, and nonalcohol-dependent individuals may be concerned not only with alcohol treatment costs but also with the effect of alcohol interventions on broader social costs and outcomes. To estimate the sum of treatment costs plus the costs of health care utilization, arrests, and motor vehicle accidents for the 9 treatments in COMBINE 3 years postrandomization. A cost study based on a randomized controlled clinical trial. : The study involved 786 participants 3 years postrandomization. Multivariate results show no significant differences in mean costs between any of the treatment arms as compared with medical management (MM) + placebo for the 3-year postrandomization sample. The median costs of MM + acamprosate, MM + naltrexone, MM + acamprosate + naltrexone, and MM + acamprosate + combined behavioral intervention were significantly lower than the median cost for MM + placebo. The results show that social cost savings are generated relative to MM + placebo by 3 years postrandomization, and the magnitude of these cost savings is greater than the costs of the COMBINE treatment received 3 years prior. Our study suggests that several alcohol treatments may indeed lead to reduced median social costs associated with health care, arrests, and motor vehicle accidents.

The effects of dexmedetomidine alone and in combination with tramadol or amitriptyline in a neuropathic pain model.

PubMed

Farghaly, Hanan Sm; Abd-Ellatief, Rasha B; Moftah, Marie Z; Mostafa, Mostafa G; Khedr, Eman M; Kotb, Hassan I

2014-01-01

Interactions between the sympathetic and somatic nervous system play an essential role in the pathophysiologic mechanisms of neuropathic pain. The α2-adrenoceptor agonists produce effective antinociception, but sedation is an important adverse effect. Multidrug therapy is potentially valuable to decrease side effects. The aim of the present study was to investigate the possible antinociceptive effect of dexmedetomidine, an α2-adrenoceptor agonist, and its combination with front-line treatment of neuropathic pain, i.e., amitriptyline or tramadol, in a chronic constriction injury (CCI) model of the sciatic nerve in rats. Controlled animal study. Following unilateral ligation of the left sciatic nerve, the effect of intraperitoneal (i.p.) dexmedetomidine (5 ug/kg), tramadol (5 mg/kg), and amitriptyline (30 mg/kg) on mechanical allodynia (measured by electrical von Frey apparatus) and hyperalgesia (measured by Randall and Selitto test) was studied. The sham-operated rats and un-operated hind paw (right paw) press normally on the floor reproduced by a weighted pain score of 0. Behavioral and mechanical tests confirmed the development of neuropathic pain after CCI. All individual drugs and dexmedetomidine combination with either tramadol or amitriptyline were effective in reducing mechanical allodynia and hyperalgesia. Dexmedetomidine, amitriptyline, tramadol, amitriptyline+dexmedetomidine, and tramadol+dexmedetomidine combination did not produce any sedation/motor impairment (P > 0.05). Although the combination of these drugs improved the CCI model of neuropathic pain in this study, an additional interpretation of the underlying mechanism(s) will be needed to confirm these findings. The combination of these drugs appears to be more effective in increasing the pain threshold after peripheral nerve injury, when compared with the administration of either of amitriptyline or tramadol alone and should be considered as a possible alternative to decrease side effects of individual drug therapy.

Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: A systematic review and meta-analysis

PubMed Central

2012-01-01

Background Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined whether the combination of pharmacological treatments and psychotherapy is associated with higher effectiveness than pharmacotherapy alone via meta-analysis; and identified possible treatment effect modifiers via meta-regression-analysis. Methods A systematic search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered. Results We identified 8 studies with a total of 9 relevant comparisons. Our analysis revealed small, but statistically not significant effects of combined therapies on outcomes directly related to depression (BR = 1.20) with substantial heterogeneity between studies (I² = 67%). Three treatment effect modifiers were identified: target disorders, the type of psychotherapy and the type of pharmacotherapy. Small but statistically significant effects of combined therapies on quality of life (SMD = 0.18) were revealed. No differences in acceptance rates and the long-term effects between combined treatments and pure pharmacological interventions were observed. Conclusions This systematic review could not provide clear evidence for the combination of pharmacotherapy and psychotherapy. However, due to the small amount of primary studies further research is needed for a conclusive decision. PMID:22694751

Combination deworming for the control of double-resistant cyathostomin parasites - short and long term consequences.

PubMed

Scare, J A; Lyons, E T; Wielgus, K M; Nielsen, M K

2018-02-15

Equine cyathostomin are pervasive gastrointestinal parasites with wide-spread resistance to the benzimidazole and tetrahydropyrimidine drug classes worldwide. Combination deworming has been proposed as a more sustainable parasite control strategy. Simulation studies have found combination deworming to be effective in controlling drug resistant ovine trichostrongylid parasites. One equine study demonstrated an additive effect of a combination of oxibendazole and pyrantel pamoate against cyathostomins. However, this is the only equine study evaluating combination therapy, and the effects of repeated combination treatments administered over time remain unknown. The purpose of this study was to observe the efficacy of repeated oxibendazole/pyrantel pamoate combination therapy administered over one year against a cyathostomin population with resistance to benzimidazole and pyrantel products. Fecal egg counts were determined for the entire herd (N = 21) at the day of anthelmintic treatment and at two-week intervals for eight weeks post treatment. Starting efficacies of oxibendazole (OBZ, 10 mg/kg) and pyrantel pamoate (PYR, 6.6 mg base/kg) were 66.7% and 63.3%, respectively. Hereafter, the herd was treated four times with an oxibendazole/pyrantel pamoate combination, eight weeks apart, followed by repeating the single active treatments before concluding the study. While the first combination treatment exhibited an additive effect of the two active ingredients, this efficacy was not sustained over the course of the study. Mean fecal egg count reduction (FECR) was significantly greater for the first combination treatment (76.6%) than the second (42.6%, p = 0.0454), third (41.6%, p = 0.0318), and fourth (40.7%, p = 0.0372) combination treatments. The final single active mean FECRs were 42.3% for oxibendazole, and 42.7% for pyrantel pamoate. These efficacies were not significantly different from the initial single active efficacies (OBZ, p = 0.4421; PYR, p = 0.8361). These results suggest that combination therapy against double resistant equine cyathostomin populations is not sustainable, when using actives with markedly decreased starting efficacies. Copyright © 2018 Elsevier B.V. All rights reserved.

Activity of Oxantel Pamoate Monotherapy and Combination Chemotherapy against Trichuris muris and Hookworms: Revival of an Old Drug

PubMed Central

Keiser, Jennifer; Tritten, Lucienne; Silbereisen, Angelika; Speich, Benjamin; Adelfio, Roberto; Vargas, Mireille

2013-01-01

Background It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations. Methodology We studied the activity of the veterinary drug oxantel pamoate against Trichuris muris, Ancylostoma ceylanicum and Necator americanus in vitro and in vivo. In addition, the dose-effect of oxantel pamoate combined with albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin was studied against T. muris in vitro and additive or synergistic combinations were followed up in vivo. Principal Findings We calculated an ED50 of 4.7 mg/kg for oxantel pamoate against T. muris in mice. Combinations of oxantel pamoate with pyrantel pamoate behaved antagonistically in vitro (combination index (CI) = 2.53). Oxantel pamoate combined with levamisole, albendazole or ivermectin using ratios based on their ED50s revealed antagonistic effects in vivo (CI = 1.27, 1.90 and 1.27, respectively). A highly synergistic effect (CI = 0.15) was observed when oxantel pamoate-mebendazole was administered to T. muris-infected mice. Oxantel pamoate (10 mg/kg) lacked activity against Ancylostoma ceylanicum and Necator americanus in vivo. Conclusion/Significance Our study confirms the excellent trichuricidal properties of oxantel pamoate. Since the drug lacks activity against hookworms it is necessary to combine oxantel pamoate with a partner drug with anti-hookworm properties. Synergistic effects were observed for oxantel pamoate-mebendazole, hence this combination should be studied in more detail. Since, of the standard drugs, albendazole has the highest efficacy against hookworms, additional investigations on the combination effect of oxantel pamoate-albendazole should be launched. PMID:23556013

[Meta-analysis on effect of combined supplementation of folic acid, vitamin B12 and B6 on risk of cardio-cerebrovascular diseases in randomized control trials].

PubMed

Lan, X; Dang, S N; Zhao, Y L; Yan, H; Yan, H

2016-07-01

To evaluate the effect of the combined supplementation of folic acid, vitamin B12 and B6 on the risk of cardio-cerebrovascular diseases. The literatures of randomized control trials about the relationship between the combined supplementation of folic acid, vitamin B12 and B6 and risk of cardio-cerebrovascular diseases from 1980 to 2014 were retrieved, and the eligible studies were screened for a Meta-analysis. The study indicators were the incidences of cardiovascular disease events, myocardial infarction and stroke. The cffect indicators were relative risk(RR)and 95% confidence interval(CI). Jadad score was used for the quality evaluation of the trials used in the study. The literatures of 11 randomized control trials, involving 26 395 patients, were used in the Meta-analysis. The combined supplementation of B vitamins had no effect on the incidence of cardiovascular disease events(RR=1.00, 95% CI: 0.94-1.07)based on 8 studies. The combined supplementation of B vitamins had no effect on the incidence of myocardial infarction(RR= 1.03, 95% CI: 0.94-1.13)based on 9 studies. The combined supplementation of B vitamins could reduce the incidence of stroke by 14%(RR=0.86, 95%CI: 0.78-0.95)based on 9 studies. Compared with the control group, Taking folic acid combined with vitamin B12 and B6 could reduce the level of homocysteine by 2.53 μmol/L(95%CI:-3.93--1.12). Subgroup analysis indicated that the follow-up time, the dosage of folic acid and vitamin B12 and B6, the history of diseases had no confounding effect on the incidence of cardio-cerebrovascular disease events. But the subgroup analysis for stroke showed that with the extension of follow-up time, the supplementation of B vitamins could reduce the risk of stroke. The effect of folic acid and B12 in small dosage seemed more significant in the prevention of stroke, while the preventive effect of B6 increased with increasing dosage. The preventive effect of combined supplementation of B vitamins was more significant for the patients with a history of cardio-cerebrovascular diseases. Taking folic acid combined with vitamin B6 and B12 might have no significant effect on the incidences of cardio-cerebrovascular disease events and myocardial infarction, but could lower the risk of stroke and the level of homocysteine.

Image-Word Pairing-Congruity Effect on Affective Responses

NASA Astrophysics Data System (ADS)

Sanabria Z., Jorge C.; Cho, Youngil; Sambai, Ami; Yamanaka, Toshimasa

The present study explores the effects of familiarity on affective responses (pleasure and arousal) to Japanese ad elements, based on the schema incongruity theory. Print ads showing natural scenes (landscapes) were used to create the stimuli (images and words). An empirical study was conducted to measure subjects' affective responses to image-word combinations that varied in terms of incongruity. The level of incongruity was based on familiarity levels, and was statistically determined by a variable called ‘pairing-congruity status’. The tested hypothesis proposed that even highly familiar image-word combinations, when combined incongruously, would elicit strong affective responses. Subjects assessed the stimuli using bipolar scales. The study was effective in tracing interactions between familiarity, pleasure and arousal, although the incongruous image-word combinations did not elicit the predicted strong effects on pleasure and arousal. The results suggest a need for further research incorporating kansei (i.e., creativity) into the process of stimuli selection.

Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity.

PubMed

Oliveira, V M; Khalil, N M; Carraro, E

2018-02-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

PubMed

Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

2017-02-01

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

Cravings as a mediator and moderator of drinking outcomes in the COMBINE Study

PubMed Central

Lendle, Samuel; van der Laan, Mark; Kaskutas, Lee Ann; Ahern, Jennifer

2014-01-01

Aims Investigators of the COMBINE (Combining Medications and Behavioral Interventions for Alcoholism) Study examined whether combining medications with a behavioral intervention would improve outcomes over monotherapies. Unexpectedly, the combination did not offer any advantage over either treatment alone. This study aimed to explain the lack of incremental benefit offered by the combination over either monotherapy by assessing the role of cravings as a treatment mediator and moderator. Design Secondary mediation and moderation analyses of COMBINE study data. Setting Eleven United States academic sites. Participants 863 patients randomized to one of four treatment groups: naltrexone (100mg/d; n=209), the Combined Behavioral Intervention (CBI, n=236), naltrexone and CBI combined (n=213), and placebo naltrexone (n=205). Measurements Percent Days Abstinent (PDA) measured between 13 and 16 weeks post-baseline. Cravings, the potential mediator/moderator, was measured at baseline, week 4 and week 12 using the Obsessive-Compulsive Drinking Scale. Findings Compared to placebo, naltrexone, CBI, and the combination all increased PDA by an additional 6–10 percentage points for those with high cravings (p<0.05 for all three treatment groups). None had significant effects on PDA for those with low cravings. The effects of all three treatments were at least partially mediated by cravings; craving reduction explained 48–53% of treatment effects (p<0.05 for all three treatment groups). Furthermore, naltrexone appeared to reduce cravings at 4 weeks, while CBI did not reduce cravings until 12 weeks. Conclusions Naltrexone and the behavioral intervention both improved abstinence by reducing cravings and were no longer effective once cravings were low. Furthermore, naltrexone reduced cravings by 4 weeks, while the behavioral intervention took longer to affect cravings. The COMBINE naltrexone + CBI combination may not have been more beneficial than either monotherapy because craving reduction was a common mechanism of both, and neither worked when cravings were low. PMID:23668624

Assessing the Combined Antibacterial Effect of Isoniazid and Rifampin on Four Mycobacterium tuberculosis Strains Using In Vitro Experiments and Response-Surface Modeling

PubMed Central

2017-01-01

ABSTRACT While isoniazid and rifampin have been the cornerstone of tuberculosis therapy caused by drug-susceptible Mycobacterium tuberculosis for more than 40 years, their combined action has never been thoroughly assessed by modern quantitative pharmacology approaches. The aims of this work were to perform in vitro experiments and mathematical modeling of the antibacterial effect of isoniazid and rifampin alone and in combination against various strains of Mycobacterium tuberculosis. After MIC determination of H37Rv and three strains belonging to the Beijing, Euro-American, and Indo-Oceanic lineages, the antibacterial effects of isoniazid and rifampin alone and in combination were studied in static time-kill experiments. A sigmoidal maximum effect model (Hill equation) and a response-surface model were used to describe the effect of the drugs alone and in combination, respectively. The killing effect of isoniazid and rifampin alone were well described by the Hill equation. Rifampin displayed a more concentration-dependent effect than isoniazid around the MIC. The pharmacodynamics parameters of each drug (maximal effect, median effect concentration, and coefficient of sigmoidicity) were quite similar between the four strains. The response-surface model from Minto et al. fit data of combined effect very well with low bias and imprecision (C. F. Minto, T. W. Schnider, T. G. Short, K. M. Gregg, A. Gentilini, Anesthesiology 92:1603–1616, 2000, https://doi.org/10.1097/00000542-200006000-00017). Response-surface modeling showed that the combined action of isoniazid and rifampin was synergistic for the H37Rv, Beijing, and Euro-American strains but only additive for the Indo-Oceanic strain. This study can serve as a motivating example for preclinical evaluation of combined action of antituberculous drugs. PMID:29061753

Mocetinostat combined with gemcitabine for the treatment of leiomyosarcoma: Preclinical correlates

PubMed Central

Braggio, Danielle; Zewdu, Abeba; Casadei, Lucia; Batte, Kara; Bid, Hemant Kumar; Koller, David; Yu, Peter; Iwenofu, Obiajulu Hans; Strohecker, Anne; Choy, Edwin; Lev, Dina; Pollock, Raphael

2017-01-01

Leiomyosarcoma (LMS) is a malignant soft tissue sarcoma (STS) with a dismal prognosis following metastatic disease. Chemotherapeutic intervention has demonstrated to have modest clinical efficacy with no curative potential in LMS patients. Previously, we demonstrated pan-HDAC inhibition to have a superior effect in various complex karyotypic sarcomas. In this study, our goal is to evaluate the therapeutic efficacy of mocetinostat alone and in combination with gemcitabine in LMS. Human leiomyosarcoma (LMS) cell lines were used for in vitro and in vivo studies. Compounds tested included the class I HDAC inhibitor, mocetinostat, and nucleoside analog, gemcitabine. MTS and clonogenic assays were used to evaluate the effect of mocetinostat on LMS cell growth. Cleaved caspase 3/7 analysis was used to determine the effects of mocetinostat on apoptosis. Compusyn software was used to determine in vitro synergy studies for the combination of mocetinostat plus gemcitabine. A LMS xenograft model in SCID mice was used to test the impact of mocetinostat alone, gemcitabine alone and the combination of mocetinostat plus gemcitabine. Mocetinostat abrogated LMS cell growth and clonogenic potential, and enhanced apoptosis in LMS cell lines. The combination of mocetinostat plus gemcitabine exhibited a synergistic effect in LMS cells in vitro. Similarly, mocetinostat combined with gemcitabine resulted in superior anti-LMS effects in vivo. Mocetinostat reduced the expression of gemcitabine-resistance markers RRM1, RRM2, and increased the expression of gemcitabine-sensitivity marker, hENT1, in LMS cells. LMS are aggressive, metastatic tumors with poor prognosis where effective therapeutic interventions are wanting. Our studies demonstrate the potential utility of mocetinostat combined with gemcitabine for the treatment of LMS. PMID:29186204

[Rational combinations of antiepileptic drugs for refractory epilepsy].

PubMed

Yoshino, Aihide

2011-04-01

Although epilepsy surgery is most effective for patients with intractable epilepsy, a majority of them is not eligible for the surgery. Most of patients with refractory epilepsy are eventually treated with polypharmacy in hope of seizure control. Therefore, rational combinations of antiepileptic drugs are needed to control intractable seizures. Drug combinations should be rationally chosen based on the evidence of synergic efficacy and on avoidance of neurotoxicity. Several clinical studies suggest that the combination of valproate with lamotrigine has synergic antiepileptic effect. It has also been reported that the combination of carbamazepine with lamotrigine paradoxically decreases efficacy and increases toxicity. Animal studies using isobolography suggest that the combinations of topiramate with lamotrigine or levetiracetam are also promising on both seizure control and neurotoxicity. Clinical research is needed to examine these combinations.

A simulator study of the combined effects of alcohol and marihuana on driving behavior--phase II

DOT National Transportation Integrated Search

1983-02-01

Author's abstract: The study described in this report investigated the effects of alcohol and marihuana, alone and in combination, on driver performance and behavior in a fully interactive driving simulator. The simulator provided the driver a comple...

A conservative method of testing whether combination analgesics produce additive or synergistic effects using evidence from acute pain and migraine.

PubMed

Moore, R A; Derry, C J; Derry, S; Straube, S; McQuay, H J

2012-04-01

Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. We tested measured effects of combination analgesics against the sum of the absolute benefits in acute pain and migraine using meta-analysis where individual components and combinations were tested against placebo in the same trials, and verified the result with meta-analyses where individual components and combinations were tested against placebo in different trials. Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects. © 2011 European Federation of International Association for the Study of Pain Chapters.

Combination of Peptide YY3–36 with GLP-17–36 amide Causes an Increase in First-Phase Insulin Secretion after IV Glucose

PubMed Central

Tan, Tricia M.; Salem, Victoria; Troke, Rachel C.; Alsafi, Ali; Field, Benjamin C. T.; De Silva, Akila; Misra, Shivani; Baynes, Kevin C. R.; Donaldson, Mandy; Minnion, James; Ghatei, Mohammad A.; Godsland, Ian F.

2014-01-01

Context: The combination of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) has been proposed as a potential treatment for diabetes and obesity. However, the combined effects of these hormones, PYY3–36 and GLP-17–36 amide, on glucose homeostasis are unknown. Objective: This study sought to investigate the acute effects of PYY3–36 and GLP-17–36 amide, individually and in combination, on insulin secretion and sensitivity. Setting and Design: Using a frequently sampled iv glucose tolerance test (FSIVGTT) and minimal modeling, this study measured the effects of PYY3–36 alone, GLP-17–36 amide alone, and a combination of PYY3–36 and GLP-17–36 amide on acute insulin response to glucose (AIRg) and insulin sensitivity index (SI) in 14 overweight human volunteers, studied in a clinical research facility. Results: PYY3–36 alone caused a small but nonsignificant increase in AIRg. GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide did increase AIRg significantly. No significant differences in SI were observed with any intervention. Conclusions: PYY3–36 lacks any significant acute effects on first-phase insulin secretion or SI when tested using an FSIVGTT. Both GLP-17–36 amide alone and the combination of PYY3–36 and GLP-17–36 amide increase first-phase insulin secretion. There does not seem to be any additive or synergistic effect between PYY3–36 and GLP-17–36 amide on first-phase insulin secretion. Neither hormone alone nor the combination had any significant effects on SI. PMID:25144632

Combining Heterogeneous Correlation Matrices: Simulation Analysis of Fixed-Effects Methods

ERIC Educational Resources Information Center

Hafdahl, Adam R.

2008-01-01

Monte Carlo studies of several fixed-effects methods for combining and comparing correlation matrices have shown that two refinements improve estimation and inference substantially. With rare exception, however, these simulations have involved homogeneous data analyzed using conditional meta-analytic procedures. The present study builds on…

Synergistic effect of green tea, cinnamon and ginger combination on enhancing postprandial blood glucose.

PubMed

Azzeh, Firas Sultan

2013-01-15

This study was maintained to determine the immediate effect of green tea, cinnamon, ginger and combination of them on postprandial glucose levels. The Glycemic Index (GI) for previous treatments was measured as an indicator for postprandial glucose pattern. Twenty-two healthy volunteers from both genders were enrolled in this study. Mean age was 21.3 years and mean BMI was 24.6 kg m(-2). For each herb and combination treatment, a concentration of 2.5% aqueous tea extract was prepared. The GI of green tea, cinnamon and ginger were 79, 63 and 72 respectively. Herbs combination exerted GI of 60, which was the lowest. Combination of these herbs showed the best lowering effect on postprandial glucose levels as compared with each herb alone. A potential synergism from the active ingredients of blended herbs was determined.

[Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. II. In vitro combined effects of sulbactam/cefoperazone with imipenem/cilastatin, cefuzonam, flomoxef, amikacin or tobramycin].

PubMed

Kouda, M; Kumagai, I; Kobayashi, J; Sugai, R; Matsuzaki, H

1991-02-01

We evaluated combined effects of sulbactam/cefoperazone (SBT/CPZ) with each of imipenem/cilastatin (IPM), cefuzonam, flomoxef, amikacin (AMK) and tobramycin (TOB) against 324 clinical strains. Through this study, we obtained the following results. 1. Against Serratia marcescens and Enterobacter cloacae, good synergism was obtained by combining SBT/CPZ with IPM, AMK, or TOB. 2. Against Pseudomonas aeruginosa, good synergism was obtained by combining SBT/CPZ with AMK or TOB. 3. When SBT/CPZ was used in combination with IPM, antagonism was observed among about 45% of strains of P. aeruginosa.

Systematic Review and Meta-Analysis of Randomized Clinical Trials in the Treatment of Human Brucellosis

PubMed Central

Solís García del Pozo, Julián; Solera, Javier

2012-01-01

Background Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance. Methods and Findings A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05–4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81–4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63–2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future. Conclusions Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice. PMID:22393379

5-fluorouracil enhances the antitumor effect of sorafenib and sunitinib in a xenograft model of human renal cell carcinoma.

PubMed

Miyake, Makito; Anai, Satoshi; Fujimoto, Kiyohide; Ohnishi, Sayuri; Kuwada, Masaomi; Nakai, Yasushi; Inoue, Takeshi; Tomioka, Atsushi; Tanaka, Nobumichi; Hirao, Yoshihiko

2012-06-01

Sorafenib and sunitinib are multi-kinase inhibitors with antitumor activity in patients with advanced renal cell carcinoma (RCC). Several studies have evaluated the effect of sorafenib/sunitinib in combination with chemotherapeutic agents in different types of tumor. However, few studies have addressed the activity of fluorinated pyrimidine in combination with sorafenib/sunitinib. In this study, we examined the potential of combination therapy with 5FU and sorafenib/sunitinib in human RCC cell lines. Three human RCC cell lines, ACHN, Caki-1 and Caki-2, were used to assess sensitivity to 5-fluorouracil (5FU), sorafenib and sunitinib alone or in combination using an in vitro cell survival assay. Caki-2 cells demonstrated significantly higher resistance to 5FU and sorafenib as compared to ACHN and Caki-1. Additive antitumor effects of the combination therapy were observed in the in vitro study. There was a tendency for a positive correlation between the sensitivity to sunitinib and platelet-derived growth factor β (PDGFR-β) expression levels, which were examined by reverse transcription polymerase chain reaction. Caki-1 xenograft models were prepared by inoculating cells subcutaneously into nude mice, which were divided randomly into six groups: control, 5FU (8 mg/kg/day, intraperitoneally), sorafenib (15 mg/kg/day, orally), sunitinib (20 mg/kg/day, orally), and 5FU with sorafenib or sunitinib. The treatments were administered on 5 days each week, and tumor growth was monitored for 42 days following inoculation of cells. Synergistic antitumor effects of the combination therapy were observed in an in vivo study. The resected tumors were evaluated using the Ki-67 labeling index and microvessel density. Both the Ki-67 labeling index and microvessel density were decreased in tumors treated with the combination therapy compared to those treated with sorafenib/sunitinib alone. These findings suggest that the combination therapy of 5FU with sorafenib/sunitinib may be an effective therapeutic modality for advanced RCC patients.

Orthographic Combinability and Phonological Consistency Effects in Reading Chinese Phonograms: An Event-Related Potential Study

ERIC Educational Resources Information Center

Hsu, Chun-Hsien; Tsai, Jie-Li; Lee, Chia-Ying; Tzeng, Ovid J. -L.

2009-01-01

In this study, event-related potentials (ERPs) were used to trace the temporal dynamics of phonological consistency and phonetic combinability in the reading of Chinese phonograms. The data showed a significant consistency-by-combinability interaction at N170. High phonetic combinability characters elicited greater negativity at N170 than did low…

Antinociceptive interactions of triple and quadruple combinations of endogenous ligands at the spinal level.

PubMed

Horvath, Gyongyi; Kekesi, Gabriella; Tuboly, Gabor; Benedek, Gyorgy

2007-06-25

A very interesting and rapidly developing field of pain research is related to the roles of different endogenous ligands. This study determined the antinociceptive interactions of triple and quadruple combinations of different endogenous ligands (endomorphin-1, adenosine, agmatine and kynurenic acid) on carrageenan-induced inflammatory pain model at the spinal level. Intrathecal infusion (60 min) of these drugs alone, in double, triple or quadruple combinations, was followed by a 60-min observation period. During the infusion, antihyperalgesic effect of 0.3 microg/min endomorphin-1 was higher in the triple combinations than those in the double combinations. After cessation of drug administration, only the combination of 0.3 microg/min endomorphin-1, 1 microg/min agmatine, and 0.3 microg/min adenosine was more effective than the double combinations. In quadruple combinations, the antinociceptive effects of both 0.1 and 0.3 microg/min endomorphin-1 were significantly potentiated by the otherwise ineffective triple combination of adenosine, agmatine, and kynurenic acid. No side effects could be observed at these doses. These results demonstrate that triple and quadruple combinations of these endogenous ligands caused more effective antihyperalgesia compared with double combinations. Accordingly, the doses of these substances could be further reduced, thus, reinforcing the view that complex activation and/or inhibition of different systems can be sufficiently effective in blocking nociception without adverse effects. Because all of these drugs had effects on various receptors and systems, the possible types of these interactions were discussed.

Effect of Cordyceps sinensis and taurine either alone or in combination on streptozotocin induced diabetes.

PubMed

El Zahraa Z El Ashry, Fatma; Mahmoud, Mona F; El Maraghy, Nabila N; Ahmed, Ahmed F

2012-03-01

The present study aimed to investigate the antidiabetic effects of Cordyceps sinensis, taurine and their combination in comparison with glibenclamide both in vivo and in vitro using streptozotocin rat model. The diabetic rats were orally given glibenclamide, C. sinensis, taurine or Cordyceps and taurine combination for 21 days. Their effects were studied both in vivo and in vitro. Oral administration of Cordyceps, taurine and their combination decreased serum glucose, fructosamine, total cholesterol, triglycerides levels, insulin resistance index and pancreatic malondialdehyde content. Cordyceps significantly increased serum insulin, HDL-cholesterol, total antioxidant capacity levels, β cell function percent, and pancreatic reduced glutathione (GSH) content. However, taurine was unable to elevate pancreatic GSH level to a significant level. These natural products and their combinations were more effective than glibenclamide in reducing insulin resistance index and they had stronger antioxidant properties. Cordyceps and taurine significantly enhanced glucose uptake by diaphragms of normal and diabetic rats in absence and presence of insulin. In conclusion, Cordyceps and taurine either alone or in combination have less potent hypoglycemic effects than glibenclamide; however, they have more ability to reduce insulin resistance and stronger antioxidant properties. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ambroxol Hydrochloride Combined with Fluconazole Reverses the Resistance of Candida albicans to Fluconazole.

PubMed

Li, Xiuyun; Zhao, Yuanhao; Huang, Xin; Yu, Cuixiang; Yang, Yilei; Sun, Shujuan

2017-01-01

In this study, we found that ambroxol hydrochloride (128 μg/mL) exhibits synergistic antifungal effects in combination with fluconazole (2 μg/mL) against resistant planktonic Candida albicans ( C. albicans ) cells. This combination also exhibited synergistic effects against resistant C. albicans biofilms in different stages (4, 8, and 12 h) according to the microdilution method. In vitro data were further confirmed by the success of this combination in treating Galleria mellonella infected by resistant C. albicans . With respect to the synergistic mechanism, our result revealed that ambroxol hydrochloride has an effect on the drug transporters of resistant C. albicans , increasing the uptake and decreasing the efflux of rhodamine 6G, a fluorescent alternate of fluconazole. This is the first study to investigate the in vitro and in vivo antifungal effects, as well as the possible synergistic mechanism of ambroxol hydrochloride in combination with fluconazole against resistant C. albicans . The results show the potential role for this drug combination as a therapeutic alternative to treat resistant C. albicans and provide insights into the development of antifungal targets and new antifungal agents.

Diet or exercise interventions vs combined behavioral weight management programs: a systematic review and meta-analysis of direct comparisons.

PubMed

Johns, David J; Hartmann-Boyce, Jamie; Jebb, Susan A; Aveyard, Paul

2014-10-01

Weight loss can reduce the health risks associated with being overweight or obese. However, the most effective method of weight loss remains unclear. Some programs emphasize physical activity, others diet, but existing evidence is mixed as to whether these are more effective individually or in combination. We aimed to examine the clinical effectiveness of combined behavioral weight management programs (BWMPs) targeting weight loss in comparison to single component programs, using within study comparisons. We included randomized controlled trials of combined BWMPs compared with diet-only or physical activity-only programs with at least 12 months of follow-up, conducted in overweight and obese adults (body mass index ≥25). Systematic searches of nine databases were run and two reviewers extracted data independently. Random effects meta-analyses were conducted for mean difference in weight change at 3 to 6 months and 12 to 18 months using a baseline observation carried forward approach for combined BWMPs vs diet-only BWMPs and combined BWMPs vs physical activity-only BWMPs. In total, eight studies were included, representing 1,022 participants, the majority of whom were women. Six studies met the inclusion criteria for combined BWMP vs diet-only. Pooled results showed no significant difference in weight loss from baseline or at 3 to 6 months between the BWMPs and diet-only arms (-0.62 kg; 95% CI -1.67 to 0.44). However, at 12 months, a significantly greater weight-loss was detected in the combined BWMPs (-1.72 kg; 95% CI -2.80 to -0.64). Five studies met the inclusion criteria for combined BWMP vs physical activity-only. Pooled results showed significantly greater weight loss in the combined BWMPs at 3 to 6 months (-5.33 kg; 95% CI -7.61 to -3.04) and 12 to 18 months (-6.29 kg; 95% CI -7.33 to -5.25). Weight loss is similar in the short-term for diet-only and combined BWMPs but in the longer-term weight loss is increased when diet and physical activity are combined. Programs based on physical activity alone are less effective than combined BWMPs in both the short and long term. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Inactivation of nuclear factor κB by MIP-based drug combinations augments cell death of breast cancer cells.

PubMed

Subramaniam, Menaga; Liew, Su Ki; In, Lionel LA; Awang, Khalijah; Ahmed, Niyaz; Nagoor, Noor Hasima

2018-01-01

Drug combination therapy to treat cancer is a strategic approach to increase successful treatment rate. Optimizing combination regimens is vital to increase therapeutic efficacy with minimal side effects. In the present study, we evaluated the in vitro cytotoxicity of double and triple combinations consisting of 1'S-1'-acetoxychavicol acetate (ACA), Mycobacterium indicus pranii (MIP) and cisplatin (CDDP) against 14 various human cancer cell lines to address the need for more effective therapy. Our data show synergistic effects in MCF-7 cells treated with MIP:ACA, MIP:CDDP and MIP:ACA:CDDP combinations. The type of interaction between MIP, ACA and CDDP was evaluated based on combination index being <0.8 for synergistic effect. Identifying the mechanism of cell death based on previous studies involved intrinsic apoptosis and nuclear factor kappa B (NF-κB) and tested in Western blot analysis. Inactivation of NF-κB was confirmed by p65 and IκBα, while intrinsic apoptosis pathway activation was confirmed by caspase-9 and Apaf-1 expression. All combinations confirmed intrinsic apoptosis activation and NF-κB inactivation. Double and triple combination regimens that target induction of the same death mechanism with reduced dosage of each drug could potentially be clinically beneficial in reducing dose-related toxicities.

Combined Effects of Cadmium Exposure and Temperature on the Annual Killifish Nothobranchius furzeri.

PubMed

Philippe, Charlotte; Hautekiet, Pauline; Grégoir, Arnout F; Thoré, Eli S J; Pinceel, Tom; Stoks, Robby; Brendonck, Luc; De Boeck, Gudrun

2018-06-07

Freshwater organisms are increasingly exposed to combinations of stressors. However, since it is time-consuming and costly, research on the interaction of stressors, such as compound toxicity and global warming on vertebrates, is scarce. Studies on multigenerational effects of these combined stressors are almost non-existent. Here, we tested the combined effects of 4 °C warming and cadmium exposure on life history traits, biomarkers, bio-accumulation and multigenerational tolerance in the turquoise killifish Nothobranchius furzeri. The extremely short life cycle of this vertebrate model allows for assessment of sublethal and multigenerational effects within four months. The applied cadmium concentrations had only limited effects on the measured endpoints, which suggests that N. furzeri is more resistant to cadmium than fathead minnow and rainbow trout. In contrast, the temperature increase of 4 °C was stressful: it delayed female maturation and lowered adult mass and fecundity. Finally, indications of synergistic effects were found on peak fecundity and embryonic survival. Overall, these results indicate the importance of studying chronic and multigenerational effects of combined stressors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

In vitro activities of ciprofloxacin and rifampin alone and in combination against growing and nongrowing strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus.

PubMed Central

Bahl, D; Miller, D A; Leviton, I; Gialanella, P; Wolin, M J; Liu, W; Perkins, R; Miller, M H

1997-01-01

We characterized the effects of ciprofloxacin and rifampin alone and in combination on Staphylococcus aureus in vitro. The effects of drug combinations (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition were compared by disk approximation studies and by determining the fractional inhibitory concentrations. Bactericidal effects in log-phase bacteria and in nongrowing isolates were characterized by time-kill methods. The effect of drug combinations was dependent upon whether or not cells were growing and whether killing or growth inhibition was the endpoint used to measure drug interaction. Despite bactericidal antagonism in time-kill experiments, our in vitro studies suggest several possible explanations for the observed benefits in patients treated with a combination of ciprofloxacin and rifampin for deep-seated staphylococcal infections. Notably, when growth inhibition rather than killing was used to characterize drug interaction, indifference rather than antagonism was observed. An additive bactericidal effect was observed in nongrowing bacteria suspended in phosphate-buffered saline. While rifampin antagonized the bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the bactericidal effects of rifampin. Each antimicrobial prevented the emergence of subpopulations that were resistant to the other. PMID:9174186

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

Due to the limitation of osteoporosis therapy, the alternative therapies from natural sources have been considered. In this study, we aimed to determine the antiosteoporotic effect of the combined extract of Morus alba and Polygonum odoratum leaves. Ovariectomized rats, weighing 200–220 g, were orally given the combined extract at doses of 5, 150, and 300 mg·kg−1 BW for 3 months. At the end of study, blood was collected to determine serum osteocalcin, calcium, and alkaline phosphatase level. In addition, tibia bone was isolated to determine bone oxidative stress markers, cortical bone thickness, and density of osteoblast. The combined extract decreased oxidative stress and osteoclast density but increased osteoblast density and cortical thickness. The elevation of serum calcium, alkaline phosphatase, and osteocalcin was also observed. These results suggested the antiosteoporotic effect of the combined extract via the increased growth formation together with the suppression of bone resorption. However, further studies concerning chronic toxicity and the underlying mechanism are required. PMID:25478061

A cost-effectiveness analysis of fixed-combination therapies in patients with open-angle glaucoma: a European perspective.

PubMed

Hommer, A; Wickstrøm, J; Friis, M M; Steeds, C; Thygesen, J; Ferreras, A; Gouws, P; Buchholz, P

2008-04-01

To compare the efficacy and cost implications of the use of the intraocular pressure-lowering prostaglandin analogues bimatoprost, travoprost, and latanoprost as fixed-combination therapies with timolol, a beta-adrenergic receptor antagonist. A decision analytic cost-effectiveness model was constructed. Since no head-to-head studies comparing the three treatment options exist, the analysis was based on an indirect comparison. Hence, the model was based on efficacy data from five randomized, controlled, clinical studies. The studies were comparable with respect to study design, time horizon, patient population and type of end point presented. The measure of effectiveness was the percentage reduction of the intraocular pressure level from baseline. The cost evaluated was the cost of medication and clinical visits to the ophthalmologist. All drug costs were market prices inclusive of value-added tax, and visit costs were priced using official physician fees. Cost-effectiveness analyses were carried out in five European countries: Spain, Italy, United Kingdom, Norway and Sweden. The time horizon for the analyses was 3 months. The analysis showed that fixed-combination bimatoprost/timolol was more effective and less costly than fixed-combination travoprost/timolol and fixed-combination latanoprost/timolol in three out of the five countries analyzed. In two countries, bimatoprost/timolol was less costly than latanoprost/timolol, and cost the same as travoprost/timolol. This cost-effectiveness analysis showed that the fixed combination of bimatoprost 0.03%/timolol 0.5% administered once daily was a cost-effective treatment option for patients with primary open-angle glaucoma. This study was limited by available clinical data: without a head-to-head trial, indirect comparisons were necessary. In the United Kingdom, Sweden, Norway, Italy, and Spain, from a health service viewpoint, bimatoprost/timolol was a slightly more effective as well as less costly treatment strategy when compared to both travoprost/timolol and latanoprost/timolol.

The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.

PubMed

An, Jingang; Zhang, Dingwei; Wu, Jiawen; Li, Jiong; Teng, Xiu; Gao, Xiaomin; Li, Ruilian; Wang, Xiuying; Xia, Linlin; Xia, Yumin

2017-07-01

Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control. Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs. Human primary keratinocytes and hepatic stellate cells were used for analyzing their effect in vitro. The results showed that the combination therapy exhibited higher effectiveness in remitting skin lesion, but did not significantly affect the liver function of both patients and mice. Moreover, the combination groups showed less elevation of profibrotic factors in sera when compared with methotrexate alone groups accordingly. Furthermore, primary keratinocytes expressed more involucrin as well as loricrin and proliferated more slowly on the combined stimulation. Interestingly, such combination treatment induced lower expression of profibrotic factors in hepatic stellate cells. In conclusion, the acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve higher effectiveness and result in less liver fibrosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells.

PubMed

Hirakawa, Hirokazu; Fujisawa, Hiroshi; Masaoka, Aya; Noguchi, Miho; Hirayama, Ryoichi; Takahashi, Momoko; Fujimori, Akira; Okayasu, Ryuichi

2015-03-01

Hsp90 inhibitors have become well-studied antitumor agents for their selective property against tumors versus normal cells. The combined treatment of Hsp90 inhibitor and conventional photon radiation also showed more effective tumor growth delay than radiation alone. However, little is known regarding the combined treatment of Hsp90 inhibitor and heavy-ion irradiation. In this study, SQ5 human lung tumor cells were used in vitro for clonogenic cell survival and in vivo for tumor growth delay measurement using a mouse xenograft model after 17-allylamino-17-demethoxygeldanamycin (17AAG) pretreatment and carbon ion irradiation. Repair of DNA double strand breaks (DSBs) was also assessed along with expressions of DSB repair-related proteins. Cell cycle analysis after the combined treatment was also performed. The combined treatment of 17AAG and carbon ions revealed a promising treatment option in both in vitro and in vivo studies. One likely cause of this effectiveness was shown to be the inhibition of homologous recombination repair by 17AAG. The more intensified G2 cell cycle delay was also associated with the combined treatment when compared with carbon ion treatment alone. Our findings indicate that the combination of Hsp90 inhibition and heavy-ion irradiation provides a new effective therapeutic alternative for treatment of solid tumors. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Interactions between imidazoline I2 receptor ligands and acetaminophen in adult male rats: antinociception and schedule-controlled responding

PubMed Central

Siemian, Justin N.; Li, Jiuzhou; Zhang, Yanan; Li, Jun-Xu

2015-01-01

Rationale Recent evidence suggests that imidazoline I2 receptor ligands are suitable for combination therapy with opioids. Quantitative analysis of I2 receptor ligands combined with non-opioid drugs is necessary for justification of alternative pain therapies. Objective This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with acetaminophen. Methods Von Frey and Hargreaves tests were used to examine the anti-hyperalgesic effects of drugs in complete Freund’s adjuvant (CFA)-induced inflammatory pain in rats. Food-reinforced schedule-controlled responding was used to assess the rate-suppressing effects of study drugs. Dose-addition and isobolographic analyses were used to assess drug-drug interactions for all assays. Results 2-BFI (3.2–17.8 mg/kg, i.p.), phenyzoline (17.8–100 mg/kg, i.p.), and acetaminophen (56–178 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and acetaminophen produced infra-additive to additive interactions while phenyzoline and acetaminophen produced additive to supra-additive interactions. The same drug combinations suppressed response rate in a supra-additive manner. Conclusions Quantitative analysis of the anti-hyperalgesic and response rate-suppressing effects suggests that I2 receptor ligands are not well suited to combination therapy with acetaminophen. PMID:26613734

Anti-tumorigenic activity of five culinary and medicinal herbs grown under greenhouse conditions and their combination effects.

PubMed

Yi, Weiguang; Wetzstein, Hazel Y

2011-08-15

Herbs and spices have been used as food preservatives, flavorings, and in traditional medicines for thousands of years. More and more scientific evidence supports the medicinal properties of culinary herbs. Colon cancer is the third leading cause of cancer death in the USA, and the fourth most common form of cancer worldwide. The objectives of this study were to evaluate the antitumor activity of five selected herbs grown under greenhouse conditions, and to study the potential synergistic effects among different herbal extract combinations. Thyme, rosemary, sage, spearmint, and peppermint extracts significantly inhibited SW-480 colon cancer cell growth, with sage extracts exhibiting the highest bioactivity, with 50% inhibition at 35.9 µg mL⁻¹, which was equivalent to 93.9 µg dried leaves mL⁻¹ of culture medium. Some mixtures of different herbal extracts had combination effects on cancer cell growth. The inhibitory effects of peppermint + sage combinations at a 1:1 ratio were significantly higher than rosemary + sage combinations at 1:1 ratio, although peppermint extracts showed lower inhibition than rosemary extracts. Extracts from herb species (thyme, rosemary, sage, spearmint and peppermint) can significantly inhibit the growth of human colon cancer cells. Mixtures of herb extracts can have combination effects on cancer cell growth. The study suggests that these five herbs may have potential health benefits to suppress colon cancer. Copyright © 2011 Society of Chemical Industry.

Effects of combined physical and cognitive training on fitness and neuropsychological outcomes in healthy older adults

PubMed Central

Desjardins-Crépeau, Laurence; Berryman, Nicolas; Fraser, Sarah A; Vu, Thien Tuong Minh; Kergoat, Marie-Jeanne; Li, Karen ZH; Bosquet, Laurent; Bherer, Louis

2016-01-01

Purpose Physical exercise and cognitive training have been shown to enhance cognition among older adults. However, few studies have looked at the potential synergetic effects of combining physical and cognitive training in a single study. Prior trials on combined training have led to interesting yet equivocal results. The aim of this study was to examine the effects of combined physical and cognitive interventions on physical fitness and neuropsychological performance in healthy older adults. Methods Seventy-six participants were randomly assigned to one of four training combinations using a 2×2 factorial design. The physical intervention was a mixed aerobic and resistance training program, and the cognitive intervention was a dual-task (DT) training program. Stretching and toning exercises and computer lessons were used as active control conditions. Physical and cognitive measures were collected pre- and postintervention. Results All groups showed equivalent improvements in measures of functional mobility. The aerobic–strength condition led to larger effect size in lower body strength, independently of cognitive training. All groups showed improved speed of processing and inhibition abilities, but only participants who took part in the DT training, independently of physical training, showed increased task-switching abilities. The level of functional mobility after intervention was significantly associated with task-switching abilities. Conclusion Combined training did not yield synergetic effects. However, DT training did lead to transfer effects on executive performance in neuropsychological tests. Both aerobic-resistance training and stretching-toning exercises can improve functional mobility in older adults. PMID:27698558

Can the Medical-nursing Combined Care Promote the Accessibility of Health Services for the Elderly in Nursing Home? A Study Protocol of Analysis of the Effectiveness Regarding Health Service Utilization, Health Status and Satisfaction with Care.

PubMed

Bao, J; Wang, X-J; Yang, Y; Dong, R-Q; Mao, Z-F

2015-12-01

Currently, segmentation of healthcare and daily care for the elderly living in nursing homes usually results in the elderly not getting medical treatment timely and effectively. The medical-nursing combined care, which has been put into practice in several areas in China, is developed to enhance the accessibility of healthcare for the elderly. The aim of the study is to explore the effectiveness of the new care service, based on Andersen model, regarding health service utilization, health status and service satisfaction. The effectiveness of medical-nursing combined care will be measured in a cross-sectional study in nine nursing homes in Jianghan District, Wuhan, China, with 1067 old residents expected to participate. The questionnaire containing items of demographics, health service use, service satisfaction and instrument of SF-36 V2 is developed based on the conceptual framework of Andersen behaviour model of health service utilization. Descriptive analysis, variance analysis, multiple factors analysis, and correlation analysis will be performed to compare the sociological characteristics, health service use, health status and service satisfaction of the elderly living in different modes of nursing homes, to explore the influence factors of care effectiveness, as well as to study the relationship between health behaviour and health outcomes. The study design of analysing the effects of medical-nursing combined care and performing the horizontal comparison among the nursing homes under the framework of Andersen model is blazing new trails. Recruitment and design of questionnaire are important issues. Successful data collection and quality control are also necessary. Taking these into account, this study is estimated to provide evidence for the effectiveness of medical-nursing combined care service in China.

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

PubMed Central

Yasmin-Karim, Sayeda; Moreau, Michele; Mueller, Romy; Sinha, Neeharika; Dabney, Raymond; Herman, Allen; Ngwa, Wilfred

2018-01-01

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed. PMID:29740535

Combination Pharmacotherapies for Stimulant Use Disorder: A Review of Clinical Findings and Recommendations for Future Research

PubMed Central

Stoops, William W.; Rush, Craig R.

2014-01-01

Despite concerted efforts to identify a pharmacotherapy for managing stimulant use disorders, no widely effective medications have been approved. Innovative strategies are necessary to develop successful pharmacotherapies for stimulant use disorders. This manuscript reviews human laboratory studies and clinical trials to determine whether one such strategy, use of combination pharmacotherapies, holds promise. The extant literature shows that combination pharmacotherapy produced results that were better than placebo treatment, especially with medications shown to have efficacy as monotherapies. However, many studies did not compare individual constituents to the combination treatment, making it impossible to determine whether combination treatment is more effective than monotherapy. Future research should systematically compare combined treatments with individual agents using medications showing some efficacy when tested alone. PMID:24716825

Synergistic antibacterial and antibiofilm efficacy of nisin in combination with p-coumaric acid against food-borne bacteria Bacillus cereus and Salmonella typhimurium.

PubMed

Bag, A; Chattopadhyay, R R

2017-11-01

The aim of the study was to evaluate possible antibacterial and antibiofilm efficacy of a bacteriocin, nisin with two essential oil components linalool and p-coumaric acid in combination against food-borne bacteria Bacillus cereus and Salmonella typhimurium. Their inhibition effects on planktonic cells and preformed biofilms were evaluated using microbroth dilution and checkerboard titration methods. Nisin/p-coumaric acid combination showed synergistic effects against planktonic cells of both the studied bacteria, whereas nisin/linalool combination showed synergistic activity against B. cereus and additive effect against S. typhimurium. In preformed biofilms, nisin by itself failed to show >50% antibiofilm efficacy against both the studied bacteria, but in combination with linalool and p-coumaric acid, it exerted >50% antibiofilm efficacy. On the basis of fractional inhibitory concentration indices values, nisin/p-coumaric acid combination exhibited synergistic antibiofilm activity, whereas nisin/linalool combination showed additive effects against preformed biofilms of studied bacteria. The results provide evidence that p-coumaric acid due to its synergistic interactions with nisin against planktonic cells and biofilms of both Gram-positive and Gram-negative food-borne bacteria enhanced the antibacterial spectrum of nisin, which subsequently may facilitate their use in the food industry. In the present work, synergistic interactions between a bacteriocin, nisin and essential oil component p-coumaric acid on planktonic cells as well as on biofilms of Gram-positive and Gram-negative food-borne bacteria have been reported. The results of this study provide evidence that nisin/p-coumaric acid combination can be considered as a promising source for development of more potent broad spectrum antimicrobial blend for food preservation, which subsequently may facilitate their use in the food industry. To the best of our knowledge, this is the first report of the antibacterial and antibiofilm efficacy of nisin in combination with essential oil components against food-borne bacteria. © 2017 The Society for Applied Microbiology.

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

PubMed Central

Gu, Ha Ra; Choi, Su Jin; Lee, Jae Cheol; Kim, You Cheoul; Han, Chul Ju; Kim, Jin; Yang, Ki Young; Kim, Yeon Joo; Noh, Geum Youb; No, So Hyeon; Jeong, Jae-Hoon

2015-01-01

Background/Aims Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. Methods Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. Results Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. Conclusions Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future. PMID:25834802

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells.

PubMed

Gu, Ha Ra; Park, Su Cheol; Choi, Su Jin; Lee, Jae Cheol; Kim, You Cheoul; Han, Chul Ju; Kim, Jin; Yang, Ki Young; Kim, Yeon Joo; Noh, Geum Youb; No, So Hyeon; Jeong, Jae-Hoon

2015-03-01

Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.

Screening of antibacterial effects of anise essential oil alone and in combination with conventional antibiotics against Streptococcus pneumoniae clinical isolates.

PubMed

Gradinaru, Adina Catinca; Miron, Anca; Trifan, Adriana; Spac, A; Brebu, M; Aprotosoaie, Ana Clara

2014-01-01

This study aimed to investigate the effects of anise essential oil alone and in combination with conventional antibiotics (amoxicillin, ciprofloxacin) against Streptococcus pneumoniae clinical isolates. MATERIAL AND METHODs: Anise essential oil (AEO) was isolated by hydrodistillation from dried powdered fruits. Its chemical composition was investigated by GC-MS and GC-FID. Broth dilution assay was used to evaluate the antibacterial effects of anise essential oil. The interactions with antibiotics were studied by the checkerboard assay. Trans-anethole (90.18%) was identified as major constituent in anise essential oil. Almost all combinations AEO-amoxicillin and AEO-ciprofloxacin showed indifferent interactions (1 < FIC index < or = 2). Positive interactions (addition and weak synergism) were found only for four combinations AEO-amoxicillin (FIC index = 1,0.62, 0.75 and 0.5) and one combination AEO-ciprofloxacin (FIC index = 0.62). Herbal products containing anise essential oil may be used as expectorants in combination with amoxicillin or ciprofloxacin in Streptococcus pneumoniae infections without diminishing antibiotic efficacy.

Global statistics of liquid water content and effective number density of water clouds over ocean derived from combined CALIPSO and MODIS measurements

NASA Astrophysics Data System (ADS)

Hu, Y.; Vaughan, M.; McClain, C.; Behrenfeld, M.; Maring, H.; Anderson, D.; Sun-Mack, S.; Flittner, D.; Huang, J.; Wielicki, B.; Minnis, P.; Weimer, C.; Trepte, C.; Kuehn, R.

2007-03-01

This study presents an empirical relation that links layer integrated depolarization ratios, the extinction coefficients, and effective radii of water clouds, based on Monte Carlo simulations of CALIPSO lidar observations. Combined with cloud effective radius retrieved from MODIS, cloud liquid water content and effective number density of water clouds are estimated from CALIPSO lidar depolarization measurements in this study. Global statistics of the cloud liquid water content and effective number density are presented.

Beam combining and SBS suppression in white noise and pseudo-random modulated amplifiers

NASA Astrophysics Data System (ADS)

Anderson, Brian; Flores, Angel; Holten, Roger; Ehrenreich, Thomas; Dajani, Iyad

2015-03-01

White noise phase modulation (WNS) and pseudo-random binary sequence phase modulation (PRBS) are effective techniques for mitigation of nonlinear effects such as stimulated Brillouin scattering (SBS); thereby paving the way for higher power narrow linewidth fiber amplifiers. However, detailed studies comparing both coherent beam combination and the SBS suppression of these phase modulation schemes have not been reported. In this study an active fiber cutback experiment is performed comparing the enhancement factor of a PRBS and WNS broadened seed as a function of linewidth and fiber length. Furthermore, two WNS and PRBS modulated fiber lasers are coherently combined to measure and compare the fringe visibility and coherence length as a function of optical path length difference. Notably, the discrete frequency comb of PRBS modulation provides a beam combining re-coherence effect where the lasers periodically come back into phase. Significantly, this may reduce path length matching complexity in coherently combined fiber laser systems.

The Cost-Effectiveness and Return-On-Investment of a Combined Social and Physical Environmental Intervention in Office Employees

ERIC Educational Resources Information Center

van Dongen, J. M.; Coffeng, J. K.; van Wier, M. F.; Boot, C. R. L.; Hendriksen, I. J. M.; van Mechelen, W.; Bongers, P. M.; van der Beek, A. J.; Bosmans, J. E.; van Tulder, M. W.

2017-01-01

This study explored the cost-effectiveness and return-on-investment of a combined social and physical environmental worksite health promotion program compared with usual practice, and of both intervention conditions separately. Participants were randomized to the combined intervention (n = 92), social environmental intervention (n = 118), physical…

Quantitative Assessment of Combination Antimicrobial Therapy against Multidrug-Resistant Acinetobacter baumannii▿

PubMed Central

Lim, Tze-Peng; Ledesma, Kimberly R.; Chang, Kai-Tai; Hou, Jing-Guo; Kwa, Andrea L.; Nikolaou, Michael; Quinn, John P.; Prince, Randall A.; Tam, Vincent H.

2008-01-01

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r2 > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations. PMID:18505848

Ablative fractional carbon dioxide laser combined with intense pulsed light for the treatment of photoaging skin in Chinese population: A split-face study.

PubMed

Mei, Xue-Ling; Wang, Li

2018-01-01

Intense pulsed light (IPL) is effective for the treatment of lentigines, telangiectasia, and generalized erythema, but is less effective in the removal of skin wrinkles. Fractional laser is effective on skin wrinkles and textural irregularities, but can induce postinflammatory hyperpigmentation (PIH), especially in Asians. This study evaluated the safety and efficacy of ablative fractional laser (AFL) in combination with IPL in the treatment of photoaging skin in Asians.This study included 28 Chinese women with Fitzpatrick skin type III and IV. The side of the face to be treated with IPL alone (3 times) or AFL in combination with IPL (2 IPL treatments and 1 AFL treatment) was randomly selected. Skin conditions including hydration, transepidermal water loss, elasticity, spots, ultraviolet spots, brown spots, wrinkle, texture, pore size and red areas, as well as adverse effects were evaluated before the treatment and at 30 days after the treatment.Compared with IPL treatment alone, AFL in combination with IPL significantly increased elasticity, decreased pore size, reduced skin wrinkles, and improved skin texture (P = .004, P = .039, P = .015, and P = .035, respectively). Both treatment protocols produced similar effects in relation to the improvement of photoaging-induced pigmentation. The combined therapy did not impair epidermal barrier function. No postoperative infection, hypopigmentation, or scarring occurred after IPL and AFL treatments. PIH occurred at 1 month after AFL treatment and disappeared at 30 days after completion of the combined therapy.AFL in combination with IPL is safe and effective for photoaging skin in Asians. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.

PubMed

Shinozaki, Tomonari; Yamada, Toshihiko; Nonaka, Takahiro; Yamamoto, Tatsuo

2015-06-01

Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain. The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally. In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study. The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.

Effect of Shoes on Stiffness and Energy Efficiency of Ankle-Foot Orthosis: Bench Testing Analysis.

PubMed

Kobayashi, Toshiki; Gao, Fan; LeCursi, Nicholas; Foreman, K Bo; Orendurff, Michael S

2017-12-01

Understanding the mechanical properties of ankle-foot orthoses (AFOs) is important to maximize their benefit for those with movement disorders during gait. Though mechanical properties such as stiffness and/or energy efficiency of AFOs have been extensively studied, it remains unknown how and to what extent shoes influence their properties. The aim of this study was to investigate the effect of shoes on stiffness and energy efficiency of an AFO using a custom mechanical testing device. Stiffness and energy efficiency of the AFO were measured in the plantar flexion and dorsiflexion range, respectively, under AFO-alone and AFO-Shoe combination conditions. The results of this study demonstrated that the stiffness of the AFO-Shoe combination was significantly decreased compared to the AFO-alone condition, but no significant differences were found in energy efficiency. From the results, we recommend that shoes used with AFOs should be carefully selected not only based on their effect on alignment of the lower limb, but also their effects on overall mechanical properties of the AFO-Shoe combination. Further study is needed to clarify the effects of differences in shoe designs on AFO-Shoe combination mechanical properties.

Combination chemoprevention: future direction of colorectal cancer prevention.

PubMed

Zhou, Ping; Cheng, Shao-Wen; Yang, Rong; Wang, Bing; Liu, Jian

2012-05-01

Recent research has drawn attention to protective effects of chemopreventive agents that reverse, suppress, or prevent the carcinogenic progression using pharmacological or nutritional agents. Aspirin and celecoxib are the promising preventive agents to effectively reduce the risk of colorectal cancer, but such agents are associated with severe gastrointestinal and cardiovascular side effects in long-term administration at high doses. Recently, the strategy that combinational use with several chemopreventive agents at low doses induces greater inhibition of carcinogenesis has become the focus. The nonsteroidal anti-inflammatory drugs (NSAIDs) may combine with ornithine decarboxylase inhibitors, hydroxymethylglutaryl-CoA reductase inhibitors, epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands, and tumor necrosis factor-related apoptosis-inducing ligand, to magnify the chemoprophylactic effect. It is noteworthy that the phase III trial of difluoromethylornithine combination with sulidac has shown greater and effective preventive roles, which pave the way for the use of combinations of other agents. The long-term statins and low-dose NSAIDs have also been associated with risk reduction in vitro, in vivo, and in retrospective studies; however, the data are inconsistent. Epidermal growth factor signaling inhibitors, peroxisome proliferator-activated receptor-γ ligands and tumor necrosis factor-related apoptosis-inducing ligand have been demonstrated to potentiate the preventive effects of NSAIDs in vitro and in vivo, but these combinational regimens have not yet been applied to clinical research. The major goal of this study was to review combination chemoprevention for colorectal cancer by means of combining low doses of potential preventive agents to increase their chemoprophylaxis efficacy and to minimize toxicity.

Synergistic anticancer effects of curcumin and resveratrol in Hepa1-6 hepatocellular carcinoma cells.

PubMed

Du, Qin; Hu, Bing; An, Hong-Mei; Shen, Ke-Ping; Xu, Ling; Deng, Shan; Wei, Meng-Meng

2013-05-01

Hepatocellular carcinoma remains one of the most prevalent malignancies worldwide. Curcuma aromatica and Polygonum cuspidatum are one of the commonly used paired-herbs for liver cancer treatment. Curcumin and resveratrol are the major anticancer constituents of Curcuma aromatica and Polygonum cuspidatum, respectively. Curcumin and resveratrol have been found to exhibit a synergistic anticancer effect in colon cancer. However, the combined effect of curcumin and resveratrol against hepatocellular carcinoma remains unknown. In the present study, we evaluated the combined effects of curcumin and resveratrol in hepatocellular carcinoma Hepa1-6 cells. The results showed that curcumin and resveratrol significantly inhibited the proliferation of Hepa1-6 cells in a dose- and time-dependent manner. The combination treatment of curcumin and resveratrol elicited a synergistic antiproliferative effect in Hepa1-6 cells. The apoptosis of Hepa1-6 cells induced by the combination treatment with curcumin and resveratrol was accompanied by caspase-3, -8 and -9 activation, which was completely abrogated by a pan caspase inhibitor, Z-VAD-FMK. Combination of curcumin and resveratrol upregulated intracellular reactive oxygen species (ROS) levels in Hepa1-6 cells. The ROS scavenger, NAC, partially attenuated the apoptosis and caspase activation induced by the combination treatment of curcumin and resveratrol. In addition, the combination of curcumin and resveratrol downregulated XIAP and survivin expression. These data suggest that the combination treatment of curcumin and resveratrol is a promising novel anticancer strategy for liver cancer. The present study also provides new insights into the effective mechanism of paired-herbs in traditional Chinese medicine.

Combination monoamine oxidase inhibitor and beta-blocker treatment of migraine, with anxiety and depression.

PubMed

Merikangas, K R; Merikangas, J R

1995-11-01

This paper presents the results of a study comparing the effectiveness of a beta-adrenergic blocking agent, atenolol, a monoamine oxidase inhibitor (MAO-I), phenelzine, and the combination in treatment of 61 adults with migraine headache. The goals of the study are (1) to investigate the safety of concomitant treatment of migraine with beta-blockers and phenelzine, (2) to assess whether orthostatic hypertension and other side effects would be relieved, and (3) to compare the results of this open trial of phenelzine to those of a previous study using similar methods. Phenelzine was associated with a large decrease in the frequency and severity of migraine attacks. Anxiety and depression were also reduced by phenelzine both alone, and in combination with a beta-blocker. The results show that the combination of MAO-I's and beta-blockers can be administered safely, and can lead to the reduction in the side effects with either drug alone.

A Systematic Review of Home-Based Childhood Obesity Prevention Studies

PubMed Central

Fawole, Oluwakemi; Segal, Jodi; Wilson, Renee F.; Cheskin, Lawrence J.; Bleich, Sara N.; Wu, Yang; Lau, Brandyn; Wang, Youfa

2013-01-01

BACKGROUND AND OBJECTIVES: Childhood obesity is a global epidemic. Despite emerging research about the role of the family and home on obesity risk behaviors, the evidence base for the effectiveness of home-based interventions on obesity prevention remains uncertain. The objective was to systematically review the effectiveness of home-based interventions on weight, intermediate (eg, diet and physical activity [PA]), and clinical outcomes. METHODS: We searched Medline, Embase, PsychInfo, CINAHL, clinicaltrials.gov, and the Cochrane Library from inception through August 11, 2012. We included experimental and natural experimental studies with ≥1-year follow-up reporting weight-related outcomes and targeting children at home. Two independent reviewers screened studies and extracted data. We graded the strength of the evidence supporting interventions targeting diet, PA, or both for obesity prevention. RESULTS: We identified 6 studies; 3 tested combined interventions (diet and PA), 1 used diet intervention, 1 combined intervention with primary care and consumer health informatics components, and 1 combined intervention with school and community components. Select combined interventions had beneficial effects on fruit/vegetable intake and sedentary behaviors. However, none of the 6 studies reported a significant effect on weight outcomes. Overall, the strength of evidence is low that combined home-based interventions effectively prevent obesity. The evidence is insufficient for conclusions about home-based diet interventions or interventions implemented at home in association with other settings. CONCLUSIONS: The strength of evidence is low to support the effectiveness of home-based child obesity prevention programs. Additional research is needed to test interventions in the home setting, particularly those incorporating parenting strategies and addressing environmental influences. PMID:23753095

Failure mode effect analysis and fault tree analysis as a combined methodology in risk management

NASA Astrophysics Data System (ADS)

Wessiani, N. A.; Yoshio, F.

2018-04-01

There have been many studies reported the implementation of Failure Mode Effect Analysis (FMEA) and Fault Tree Analysis (FTA) as a method in risk management. However, most of the studies usually only choose one of these two methods in their risk management methodology. On the other side, combining these two methods will reduce the drawbacks of each methods when implemented separately. This paper aims to combine the methodology of FMEA and FTA in assessing risk. A case study in the metal company will illustrate how this methodology can be implemented. In the case study, this combined methodology will assess the internal risks that occur in the production process. Further, those internal risks should be mitigated based on their level of risks.

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse

PubMed Central

Pachauri, Vidhu; Flora, SJS

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study. PMID:26339189

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

PubMed

Pachauri, Vidhu; Flora, Sjs

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

Combination of α-Tomatine and Curcumin Inhibits Growth and Induces Apoptosis in Human Prostate Cancer Cells

PubMed Central

Li, Dongli; He, Yan; Li, Yu; Du, Zhiyun; Zhang, Kun; DiPaola, Robert; Goodin, Susan; Zheng, Xi

2015-01-01

α-Tomatine is a glycoalkaloid found in tomatoes and curcumin is a major yellow pigment of turmeric. In the present study, the combined effect of these two compounds on prostate cancer cells was studied. Treatment of different prostate cancer cells with curcumin or α-tomatine alone resulted in growth inhibition and apoptosis in a concentration-dependent manner. Combinations of α-tomatine and curcumin synergistically inhibited the growth and induced apoptosis in prostate cancer PC-3 cells. Effects of the α-tomatine and curcumin combination were associated with synergistic inhibition of NF-κB activity and a potent decrease in the expression of its downstream gene Bcl-2 in the cells. Moreover, strong decreases in the levels of phospho-Akt and phosphor-ERK1/2 were found in PC-3 cells treated with α-tomatine and curcumin in combination. In animal experiment, SCID mice with PC-3 xenograft tumors were treated with α-tomatine and curcumin. Combination of α-tomatine and curcumin more potently inhibited the growth of PC-3 tumors than either agent alone. Results from the present study indicate that α-tomatine in combination with curcumin may be an effective strategy for inhibiting the growth of prostate cancer. PMID:26630272

Use of estetrol with other steroids for attenuation of neonatal hypoxic-ischemic brain injury: to combine or not to combine?

PubMed

Tskitishvili, Ekaterine; Pequeux, Christel; Munaut, Carine; Viellevoye, Renaud; Nisolle, Michelle; Noël, Agnes; Foidart, Jean-Michel

2016-06-07

Estetrol (E4), estradiol (E2) and progesterone (P4) have important antioxidative and neuroprotective effects in neuronal system. We aimed to study the consequence of combined steroid therapy in neonatal hypoxic-ischemic encephalopathy (HIE). In vitro the effect of E4 combined with other steroids on oxidative stress and the cell viability in primary hippocampal cultures was evaluated by lactate dehydrogenase and cell survival assays. In vivo neuroprotective and therapeutic efficacy of E4 combined with other steroids was studied in HIE model of immature rats. The rat pups rectal temperature, body and brain weights were evaluated.The hippocampus and the cortex were investigated by histo/immunohistochemistry: intact cell number counting, expressions of markers for early gray matter lose, neuro- and angiogenesis were studied. Glial fibrillary acidic protein was evaluated by ELISA in blood samples. In vitro E4 and combinations of high doses of E4 with P4 and/or E2 significantly diminished the LDH activity and upregulated the cell survival.In vivopretreatment or treatment by different combinations of E4 with other steroids had unalike effects on body and brain weight, neuro- and angiogenesis, and GFAP expression in blood. The combined use of E4 with other steroids has no benefit over the single use of E4.

Overcoming IGF1R/IR Resistance Through Inhibition of MEK Signaling in Colorectal Cancer Models

PubMed Central

Flanigan, Sara A.; Pitts, Todd M.; Newton, Timothy P.; Kulikowski, Gillian N.; Tan, Aik Choon; McManus, Martine C.; Spreafico, Anna; Kachaeva, Maria I.; Selby, Heather M.; Tentler, John J.; Eckhardt, S. Gail; Leong, Stephen

2013-01-01

Purpose Results from clinical trials involving resistance to molecularly targeted therapies have revealed the importance of rational single agent and combination treatment strategies. In this study, we tested the efficacy of a type 1 insulin-like growth factor receptor (IGF1R)/insulin receptor (IR) tyrosine kinase inhibitor (TKI), OSI-906, in combination with a MEK 1/2 inhibitor based on evidence that the MAPK pathway was upregulated in colorectal cancer (CRC) cell lines that were resistant to OSI-906. Experimental Design The antiproliferative effects of OSI-906 and the MEK 1/2 inhibitor U0126, were analyzed both as single agents and in combination in 13 CRC cell lines in vitro. Apoptosis, downstream effector proteins, and cell cycle were also assessed. Additionally, the efficacy of OSI-906 combined with the MEK 1/2 inhibitor selumetinib (AZD6244, ARRY-142886), was evaluated in vivo using human CRC xenograft models. Results The combination of OSI-906 and U0126 resulted in synergistic effects in 11 out of 13 CRC cell lines tested. This synergy was variably associated with apoptosis or cell cycle arrest in addition to molecular effects on pro-survival pathways. The synergy was also reflected in the in vivo xenograft studies following treatment with the combination of OSI-906 and selumetinib. Conclusions Results from this study demonstrate synergistic antiproliferative effects in response to the combination of OSI-906 with a MEK 1/2 inhibitor in CRC cell line models both in vitro and in vivo, which supports the rational combination of OSI-906 with a MEK inhibitor in patients with CRC. PMID:24045180

Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia.

PubMed

Yang, Nae-Cherng; Chou, Chien-Wen; Chen, Chung-Yin; Hwang, Kai-Lin; Yang, Yi-Chueh

2009-01-01

The purpose of this randomized, double-blind, placebo-controlled, parallel comparison study was to evaluate the lipid-lowering effect of orally administrated nattokinase and nattokinase combined with red yeast rice (RYR) extract on blood lipids in patients with hyperlipidemia. A total of 47 patients with hyperlipidemia were assigned to one of three groups: 1. nattokinase-mono formula (50 mg/capsule), 2. combined formula of nattokinase with RYR (300 mg of extract/capsule) and 3. placebo. Subjects received a twice daily dose of two capsules for six months. The mono formula showed no effects on blood lipids until month six, while the combined formula ameliorated all of measured lipids starting from month one. In the combined group significant decreases were found with regard to: triglycerides (TG) by 15%, total cholesterol (TC) by 25%, low-density lipoprotein cholesterol (LDL-C) by 41%, TC/high-density lipoprotein cholesterol (HDL-C) ratio by 29.5%, and increases in HDL-C by 7.5%. These changes were sustained until the end of study. After controlling for baseline levels, only the combined group, but not mono group, showed a significant difference (p<0.0001) in TC, LDL-C and TC/HDL-C ratio when compared with the placebo group. In summary, this study provides long-term efficacy of nattokinase supplementation and shows that the combined formula has relatively more potent effects than the mono formula on lowering of blood lipids, suggesting that combined nattokinase with RYR will be a better neutraceutical for patients with hyperlipidemia than nattokinase alone.

Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects.

PubMed

Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

2016-03-26

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity.

Natural Co-Occurrence of Mycotoxins in Foods and Feeds and Their in vitro Combined Toxicological Effects

PubMed Central

Smith, Marie-Caroline; Madec, Stéphanie; Coton, Emmanuel; Hymery, Nolwenn

2016-01-01

Some foods and feeds are often contaminated by numerous mycotoxins, but most studies have focused on the occurrence and toxicology of a single mycotoxin. Regulations throughout the world do not consider the combined effects of mycotoxins. However, several surveys have reported the natural co-occurrence of mycotoxins from all over the world. Most of the published data has concerned the major mycotoxins aflatoxins (AFs), ochratoxin A (OTA), zearalenone (ZEA), fumonisins (FUM) and trichothecenes (TCTs), especially deoxynivalenol (DON). Concerning cereals and derived cereal product samples, among the 127 mycotoxin combinations described in the literature, AFs+FUM, DON+ZEA, AFs+OTA, and FUM+ZEA are the most observed. However, only a few studies specified the number of co-occurring mycotoxins with the percentage of the co-contaminated samples, as well as the main combinations found. Studies of mycotoxin combination toxicity showed antagonist, additive or synergic effects depending on the tested species, cell model or mixture, and were not necessarily time- or dose-dependent. This review summarizes the findings on mycotoxins and their co-occurrence in various foods and feeds from all over the world as well as in vitro experimental data on their combined toxicity. PMID:27023609

Large-scale exploration and analysis of drug combinations.

PubMed

Li, Peng; Huang, Chao; Fu, Yingxue; Wang, Jinan; Wu, Ziyin; Ru, Jinlong; Zheng, Chunli; Guo, Zihu; Chen, Xuetong; Zhou, Wei; Zhang, Wenjuan; Li, Yan; Chen, Jianxin; Lu, Aiping; Wang, Yonghua

2015-06-15

Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered. We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications. The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improving working memory in children with attention-deficit/hyperactivity disorder: the separate and combined effects of incentives and stimulant medication.

PubMed

Strand, Michael T; Hawk, Larry W; Bubnik, Michelle; Shiels, Keri; Pelham, William E; Waxmonsky, James G

2012-10-01

Working memory (WM) is considered a core deficit in Attention-Deficit/ Hyperactivity Disorder (ADHD), with numerous studies demonstrating impaired WM among children with ADHD. We tested the degree to which WM in children with ADHD was improved by performance-based incentives, an analog of behavioral intervention. In two studies, WM performance was assessed using a visuo-spatial n-back task. Study 1 compared children (ages 9-12 years) with ADHD-Combined type (n = 24) to a group of typically developing (TD) children (n = 32). Study 1 replicated WM deficits among children with ADHD. Incentives improved WM, particularly among children with ADHD. The provision of incentives reduced the ADHD-control group difference by approximately half but did not normalize WM. Study 2 examined the separate and combined effects of incentives and stimulant medication among 17 children with ADHD-Combined type. Both incentives and a moderate dose of long-acting methylphenidate (MPH; ~0.3 mg/kg t.i.d. equivalent) robustly improved WM relative to the no-incentive, placebo condition. The combination of incentives and medication improved WM significantly more than either incentives or MPH alone. These studies indicate that contingencies markedly improve WM among children with ADHD-Combined type, with effect sizes comparable to a moderate dose of stimulant medication. More broadly, this work calls attention to the role of motivation in studying cognitive deficits in ADHD and in testing multifactorial models of ADHD.

A designed screening study with prespecified combinations of factor settings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson-cook, Christine M; Robinson, Timothy J

2009-01-01

In many applications, the experimenter has limited options about what factor combinations can be chosen for a designed study. Consider a screening study for a production process involving five input factors whose levels have been previously established. The goal of the study is to understand the effect of each factor on the response, a variable that is expensive to measure and results in destruction of the part. From an inventory of available parts with known factor values, we wish to identify a best collection of factor combinations with which to estimate the factor effects. Though the observational nature of themore » study cannot establish a causal relationship involving the response and the factors, the study can increase understanding of the underlying process. The study can also help determine where investment should be made to control input factors during production that will maximally influence the response. Because the factor combinations are observational, the chosen model matrix will be nonorthogonal and will not allow independent estimation of factor effects. In this manuscript we borrow principles from design of experiments to suggest an 'optimal' selection of factor combinations. Specifically, we consider precision of model parameter estimates, the issue of replication, and abilities to detect lack of fit and to estimate two-factor interactions. Through an example, we present strategies for selecting a subset of factor combinations that simultaneously balance multiple objectives, conduct a limited sensitivity analysis, and provide practical guidance for implementing our techniques across a variety of quality engineering disciplines.« less

CETUXIMAB AND IRINOTECAN INTERACT SYNERGISTICALLY TO INHIBIT THE GROWTH OF ORTHOTOPIC ANAPLASTIC THYROID CARCINOMA XENOGRAFTS IN NUDE MICE

PubMed Central

Kim, Seungwon; Prichard, Christopher N.; Younes, Maher N.; Yazici, Yasemin D.; Jasser, Samar A.; Bekele, B. Nebiyou; Myers, Jeffrey N.

2006-01-01

Objective Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against EGFR, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model. Design The in vitro anti-proliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin. Results Cetuximab alone did not show any anti-proliferative or pro-apoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts. Conclusions Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study. PMID:16428506

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

PubMed

King, Jonathan N; Panteri, Alessandro; Graille, Melanie; Seewald, Wolfgang; Friton, Gabriele; Desevaux, Cyril

2016-06-23

Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.

Enhanced antitumor effect of curcumin liposomes with local hyperthermia in the LL/2 model.

PubMed

Tang, Jian-Cai; Shi, Hua-Shan; Wan, Li-Qiang; Wang, Yong-Sheng; Wei, Yu-Quan

2013-01-01

Curcumin previously was proven to inhibit angiogenesis and display potent antitumor activity in vivo and in vitro. In the present study, we investigated whether a combination curcumin with hyperthermia would have a synergistic antitumor effect in the LL/2 model. The results indicated that combination therapy significantly inhibited cell proliferation of MS-1 and LL/2 in vitro. LL/2 experiment model also demonstrated that the combination therapy inhibited tumor growth and prolonged the life span in vivo. Furthermore, combination therapy reduced angiogenesis and increased tumor apoptosis. Our findings suggest that the combination therapy exerted synergistic antitumor effects, providing a new perspective fpr clinical tumor therapy.

Synergistic effect of fisetin combined with sorafenib in human cervical cancer HeLa cells through activation of death receptor-5 mediated caspase-8/caspase-3 and the mitochondria-dependent apoptotic pathway.

PubMed

Lin, Ming-Te; Lin, Chia-Liang; Lin, Tzu-Yu; Cheng, Chun-Wen; Yang, Shun-Fa; Lin, Chu-Liang; Wu, Chih-Chien; Hsieh, Yi-Hsien; Tsai, Jen-Pi

2016-05-01

Combining antitumor agents with bioactive compounds is a potential strategy for improving the effect of chemotherapy on cancer cells. The goal of this study was to elucidate the antitumor effect of the flavonoid, fisetin, combined with the multikinase inhibitor, sorafenib, against human cervical cancer cells in vitro and in vivo. The combination of fisetin and sorafenib synergistically induced apoptosis in HeLa cells, which is accompanied by a marked increase in loss of mitochondrial membrane potential. Apoptosis induction was achieved by caspase-3 and caspase-8 activation which increased the ratio of Bax/Bcl-2 and caused the subsequent cleavage of PARP level while disrupting the mitochondrial membrane potential in HeLa cells. Decreased Bax/Bcl-2 ratio level and mitochondrial membrane potential were also observed in siDR5-treated HeLa cells. In addition, in vivo studies revealed that the combined fisetin and sorafenib treatment was clearly superior to sorafenib treatment alone using a HeLa xenograft model. Our study showed that the combination of fisetin and sorafenib exerted better synergistic effects in vitro and in vivo than either agent used alone against human cervical cancer, and this synergism was based on apoptotic potential through a mitochondrial- and DR5-dependent caspase-8/caspase-3 signaling pathway. This combined fisetin and sorafenib treatment represents a novel therapeutic strategy for further clinical developments in advanced cervical cancer.

An open, comparative study of 10% potassium hydroxide solution versus salicylic and lactic acid combination in the treatment of molluscum contagiosum in children.

PubMed

Köse, Osman; Özmen, İbrahim; Arca, Ercan

2013-08-01

To evaluate and compare the safety and efficacy of 10% potassium hydroxide (KOH) solution and salicylic and lactic acid (SAL + LAC) combination in the treatment of molluscum contagiosum (MC). 26 patients with MC randomized into two treatment groups. 12 patients treated with 10% KOH solution and 14 patients treated with SAL + LAC combination for 6 weeks. Parents of patients were instructed to apply medication once daily only to lesions at study onset. Assessment of response of the treated lesions and side effects was performed at 2, 4 and 6 weeks of the treatment. Newly acquired lesions were not included in the study. At the end of therapy, 83.3% (n = 10) of KOH group demonstrated complete remission and 16.7% (n = 2) of them showed partial remission; four patients (33%) developed new lesions during the study. All the patients in the SAL + LAC combination group (100%) demonstrated complete remission of study entry lesions at the end of 6 weeks with five patients (35%) acquiring new lesions during the study. Minor side effects were observed in two groups. 10% KOH solution and SAL + LAC combination were found to be equally effective in the treatment of MC in children.

Safety of the electroconvulsive therapy and amisulpride combination.

PubMed

Takács, Rozália; Iványi, Zsolt; Ungvari, Gabor S; Gazdag, Gábor

2013-03-01

Electroconvulsive therapy is frequently considered when pharmacotherapy is ineffective. In such cases the combination of the two treatment modalities are commonly used. Amisulpiride, a second generation antipsychotic drug is used in the treatment of schizophrenia and psychotic depression. When amisulpiride is ineffective as a monotherapy, combination with ECT could be an option to enhance its efficacy. To the best of our knowledge, to date there have been no data about the safety of this combination. Medical notes of all patients who were given ECT while on amisulpiride were selected from the archives of the Department of Psychiatry, Semmelweis University Medical School, Budapest, covering a 10-year period. A randomly selected matched control group was formed from patients who underwent ECT but were not taking amisulpiride. Patients in both groups also received a variety of psychotropic drugs other than amisulpide. Side effects were compared between the two groups of patients. Twenty patients received amisulpride with ECT. The most common side effects were headache, hypertension, tachycardia, nausea, dizziness, confusion, psychomotor agitation, sialorrhea, and prolonged seizure activity. All adverse effects resolved within 24 hours. No side effects of any kind were observed in 7 and 8 cases in the study and control groups, respectively. This was the first study that examined the safety of amisulpride-ECT combination in schizophrenia. Comparing the side-effects between the study and control groups, no significant differences were detected in terms of their types or frequency. The amisulpiride-ECT combination appears to be a safe treatment option.

Effects of a combined parent-student alcohol prevention program on intermediate factors and adolescents' drinking behavior: A sequential mediation model.

PubMed

Koning, Ina M; Maric, Marija; MacKinnon, David; Vollebergh, Wilma A M

2015-08-01

Previous work revealed that the combined parent-student alcohol prevention program (PAS) effectively postponed alcohol initiation through its hypothesized intermediate factors: increase in strict parental rule setting and adolescents' self-control (Koning, van den Eijnden, Verdurmen, Engels, & Vollebergh, 2011). This study examines whether the parental strictness precedes an increase in adolescents' self-control by testing a sequential mediation model. A cluster randomized trial including 3,245 Dutch early adolescents (M age = 12.68, SD = 0.50) and their parents randomized over 4 conditions: (1) parent intervention, (2) student intervention, (3) combined intervention, and (4) control group. Outcome measure was amount of weekly drinking measured at age 12 to 15; baseline assessment (T0) and 3 follow-up assessments (T1-T3). Main effects of the combined and parent intervention on weekly drinking at T3 were found. The effect of the combined intervention on weekly drinking (T3) was mediated via an increase in strict rule setting (T1) and adolescents' subsequent self-control (T2). In addition, the indirect effect of the combined intervention via rule setting (T1) was significant. No reciprocal sequential mediation (self-control at T1 prior to rules at T2) was found. The current study is 1 of the few studies reporting sequential mediation effects of youth intervention outcomes. It underscores the need of involving parents in youth alcohol prevention programs, and the need to target both parents and adolescents, so that change in parents' behavior enables change in their offspring. (c) 2015 APA, all rights reserved).

The combined effect of uranium and gamma radiation on biological responses and oxidative stress induced in Arabidopsis thaliana.

PubMed

Vanhoudt, Nathalie; Vandenhove, Hildegarde; Horemans, Nele; Wannijn, Jean; Van Hees, May; Vangronsveld, Jaco; Cuypers, Ann

2010-11-01

Uranium never occurs as a single pollutant in the environment, but always in combination with other stressors such as ionizing radiation. As effects induced by multiple contaminants can differ markedly from the effects induced by the individual stressors, this multiple pollution context should not be neglected. In this study, effects on growth, nutrient uptake and oxidative stress induced by the single stressors uranium and gamma radiation are compared with the effects induced by the combination of both stressors. By doing this, we aim to better understand the effects induced by the combined stressors but also to get more insight in stressor-specific response mechanisms. Eighteen-day-old Arabidopsis thaliana seedlings were exposed for 3 days to 10 muM uranium and 3.5 Gy gamma radiation. Gamma radiation interfered with uranium uptake, resulting in decreased uranium concentrations in the roots, but with higher transport to the leaves. This resulted in a better root growth but increased leaf lipid peroxidation. For the other endpoints studied, effects under combined exposure were mostly determined by uranium presence and only limited influenced by gamma presence. Furthermore, an important role is suggested for CAT1/2/3 gene expression under uranium and mixed stressor conditions in the leaves.

The Single and Combined Effects of Multiple Intensities of Behavior Modification and Methylphenidate for Children with Attention Deficit Hyperactivity Disorder in a Classroom Setting

ERIC Educational Resources Information Center

Fabiano, Gregory A.; Pelham, William E., Jr.; Gnagy, Elizabeth M.; Burrows-MacLean, Lisa; Coles, Erika K.; Chacko, Anil; Wymbs, Brian T.; Walker, Kathryn S.; Arnold, Fran; Garefino, Allison; Keenan, Jenna K.; Onyango, Adia N.; Hoffman, Martin T.; Massetti, Greta M.; Robb, Jessica A.

2007-01-01

Currently behavior modification, stimulant medication, and combined treatments are supported as evidence-based interventions for attention deficit hyperactivity disorder in classroom settings. However, there has been little study of the relative effects of these two modalities and their combination in classrooms. Using a within-subject design, the…

The Combined Effect of Instruction and Monitor in Improving Pronunciation of Potential English Teachers

ERIC Educational Resources Information Center

Liu, Qian; Fu, Zunwei

2011-01-01

The role that instruction and monitor can play in improvement of pronunciation has long been a focus of argument among linguists and researchers. It is assumed that their combination will result in positive effect. An empirical study is carried out and it is confirmed that their combination contributes greatly to the improvement of pronunciation…

Combining web-based tools for transparent evaluation of data for risk assessment: developmental effects of bisphenol A on the mammary gland as a case study.

PubMed

Molander, Linda; Hanberg, Annika; Rudén, Christina; Ågerstrand, Marlene; Beronius, Anna

2017-03-01

Different tools have been developed that facilitate systematic and transparent evaluation and handling of toxicity data in the risk assessment process. The present paper sets out to explore the combined use of two web-based tools for study evaluation and identification of reliable data relevant to health risk assessment. For this purpose, a case study was performed using in vivo toxicity studies investigating low-dose effects of bisphenol A on mammary gland development. The reliability of the mammary gland studies was evaluated using the Science in Risk Assessment and Policy (SciRAP) criteria for toxicity studies. The Health Assessment Workspace Collaborative (HAWC) was used for characterizing and visualizing the mammary gland data in terms of type of effects investigated and reported, and the distribution of these effects within the dose interval. It was then investigated whether there was any relationship between study reliability and the type of effects reported and/or their distribution in the dose interval. The combination of the SciRAP and HAWC tools allowed for transparent evaluation and visualization of the studies investigating developmental effects of BPA on the mammary gland. The use of these tools showed that there were no apparent differences in the type of effects and their distribution in the dose interval between the five studies assessed as most reliable and the whole data set. Combining the SciRAP and HAWC tools was found to be a useful approach for evaluating in vivo toxicity studies and identifying reliable and sensitive information relevant to regulatory risk assessment of chemicals. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Comparative study between atorvastatin and losartan on high fat diet-induced type 2 diabetes mellitus in rats.

PubMed

Mourad, Ahmed A; Heeba, Gehan H; Taye, Ashraf; El-Moselhy, Mohamed A

2013-10-01

Obesity is often associated with chronic inflammatory state which contributes to the development of insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study investigated the effects of single and combined administration of atorvastatin (ATOR, lipid-lowering drug) and losartan (LOS, angiotensin receptor antagonist) on metabolic disorders and inflammatory status that are implicated in the development of T2DM with the use of pioglitazone (PIO) as a standard antidiabetic drug. T2DM was induced in male rats by high-fat diet (HFD) feeding for 16 weeks. Oral administrations of ATOR (10 mg/kg), LOS (20 mg/kg), PIO (3 mg/kg), their binary combinations, or vehicle were started in the last 4 weeks. Fasting serum glucose, oral glucose tolerance, fasting serum insulin, IR, serum lipid profile, serum TNF-α and body composition index were determined. Results showed that all drugs and their combinations had positive impact effect on all measured parameters, and better results were achieved from binary drug combinations than administration of each drug alone. Combination of PIO with either ATOR or LOS provided better improvements on T2DM-associated metabolic abnormalities and inflammatory status with respect to each drug alone. However, the most pronounced effects of drugs and their combinations regarding the above parameters were attributed to LOS + PIO combination. In conclusion, this study indicates that combination of ATOR + PIO and, in particular, LOS + PIO can be used as promising effective therapies in the management of HFD-induced T2DM. This concept may be attributed to the combined effects of the respective monotherapies to improve lipid profile, insulin sensitivity, and TNF-α level. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Xiaofei; Zhu, Yanshuang; He, Huabin

Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTTmore » assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.« less

In-vitro activity of ciprofloxacin combined with flomoxef against Bacteroides fragilis, compared with that of ciprofloxacin combined with clindamycin.

PubMed

Kato, Komei; Iwai, Shigetomi; Sato, Takeshi; Harada, Tomohide; Nakagawa, Yoshiteru; Iwanaga, Hitomi; Ito, Yumiko; Takayama, Tadatoshi

2002-06-01

Using checkerboard and time-kill assays, the in-vitro activity of ciprofloxacin alone and in combination with flomoxef against clinical Bacteroides fragilis strains was evaluated. In addition, the microbiological efficacy of this combination was compared with that of ciprofloxacin plus clindamycin. In 88% of the 25 strains tested, the combination of ciprofloxacin plus flomoxef exhibited a synergistic or an additive effect, whereas only 56% of the 25 strains ( P< 0.01, chi(2) test) tested with the combination of ciprofloxacin plus clindamycin exhibited similar effects. In a time-kill study using 7 clinical strains, a synergistic or additive effect of the combination of ciprofloxacin plus flomoxef was observed in all 7 strains. In conclusion, the combination of ciprofloxacin plus flomoxef is very active against B. fragilis, suggesting that this combination may be very useful in the treatment of aerobic and B. fragilis mixed infections, because ciprofloxacin has an expanded spectrum against aerobes.

Dihydroartemisinin sensitizes Lewis lung carcinoma cells to carboplatin therapy via p38 mitogen-activated protein kinase activation

PubMed Central

Zhang, Bicheng; Zhang, Zhimin; Wang, Jun; Yang, Bo; Zhao, Yong; Rao, Zhiguo; Gao, Jianfei

2018-01-01

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial agent. Studies have suggested that it also exhibits anticancer effects when administered alone or in combination with conventional chemotherapeutic agents. The present study investigated the therapeutic effect of DHA combined with carboplatin (CBP) on Lewis lung carcinoma (LLC) cells and the possible underlying molecular mechanisms. MTT and clonogenic assays demonstrated that the proliferation activity of LLC cells was inhibited in a dose-dependent manner by DHA combined with CBP. In addition, flow cytometry analysis revealed that cell cycle arrest was induced at the G0/G1 phase and apoptosis was induced following treatment with the combination. When administered in combination with CBP, DHA exhibited more effective anticancer activity compared with DHA or CBP used alone, via increased apoptosis. Following treatment with DHA with or without CBP, the expression of phosphorylated-p38 mitogen-activated protein kinase (MAPK), which can be inhibited with the selective inhibitor SB202190, was detected by western blotting. To summarize, the results of the present study indicated that DHA may sensitize LLC cells to CBP therapy via the activation of p38MAPK, which suggests that a combined treatment of DHA and CBP may be a potential novel therapeutic schedule for lung adenocarcinoma. PMID:29740482

Enhanced antioxidant activity of gold nanoparticle embedded 3,6-dihydroxyflavone: a combinational study

NASA Astrophysics Data System (ADS)

Medhe, Sharad; Bansal, Prachi; Srivastava, Man Mohan

2014-02-01

The antioxidative effect of selected dietary compounds (3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine) was determined in single and combination using DPPH (2,2-diphenyl-l-picrylhydrazyl), OH (hydroxyl), H2O2 (hydrogen peroxide) and NO (nitric oxide) radical scavenging assays. Radical scavenging effect of the dietary phytochemicals individually are found to be in the order: ascorbic acid (standard) > lutein > 3,6-dihydroxyflavone > selenium methyl selenocysteine, at concentration 100 μg/ml, confirmed by all the four bioassays (p < 0.05). Among the various combinations studied, the triplet combination of 3,6-dihydroxyflavone, lutein and selenium methyl selenocysteine (1:1:1), exhibited enhancement in the target activity at same concentration level. Synthesized gold nanoparticle embedded 3,6-dihydroxyflavone further enhanced the target antioxidant activity. The combinational study including gold nanoparticle embedded 3,6-dihydroxyflavone with other native dietary nutrients showed remarkable increase in antioxidant activity at the same concentration level. The present in vitro study on combinational and nanotech enforcement of dietary phytochemicals shows the utility in the architecture of nanoparticle embedded phytoproducts having a wide range of applications in medical science.

[Search for antimicrobial agents and their various combinations that are effective in relation to the main microfloral representatives in the burn wound].

PubMed

Kataev, S V; Brodinova, N S; Moroz, A F

1980-03-01

Activity of 10 antibiotics, 6 surface active substances, 1 antioxidant and boric acid against P. aeruginosa, E. coli, Pr. vulgaris and Staph. aureus most frequently vegetating in burn wounds was studied. It was found that gentamicin had the highest antibacterial effect on the above organisms. Polymyxin M had a pronounced antimicrobial action on P. aeruginosa and E. coli. A significant antibacterial effect with respect to Staph. aureus, E. coli and Pr. vulgaris was observed with the use of the drugs of the nitrofuran line, i.e. salaful, furagin and furacillin. These drugs were not active against P. aeruginosa. A high antimicrobial effect with respect to all of the test-microbed used was recorded with methacyl, a surface active substance. To show the synergistic effect on the microbes most frequently vegetating in burn wounds, the antibacterial action of the drug combinations was studied. The synergistic effect (16 to 100 times) was observed with the use of polymyxin M combination with mafenide, carbenicillin with gentamicin, methacide with fenozan. The microorganisms tested were resistant to boric acid. On the basis of the study the most effective drugs and their combinations were chosen for their addition to the algipores (polymer coatings) used in treatment of burns infected with the above microbes.

Mindfulness-based relapse prevention combined with virtual reality cue exposure for methamphetamine use disorder: Study protocol for a randomized controlled trial.

PubMed

Chen, Xi Jing; Wang, Dong Mei; Zhou, Li Dan; Winkler, Markus; Pauli, Paul; Sui, Nan; Li, Yong Hui

2018-04-19

Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. ChiCTR-INR-17013041. Copyright © 2018 Elsevier Inc. All rights reserved.

The effect of CMC and arabic gum stabilizer combination on the characteristics of soursop velva (Annona muricata L.)

NASA Astrophysics Data System (ADS)

Parnanto, N. H. R.; Yudhistira, B.; Pertiwi, S. R.; Pangestika, A.

2018-03-01

The aims of this study were to determine the effect of the combination of CMC and Arabic Gum stabilizer toward the soursop velva characteristics and to determine the best stabilizer combination of soursop velva. This study was performed using Completely Randomized Design (CRD) with one factor: combination of CMC and Arabic Gum stabilizer using two sample replications and the analysis was repeated three times. The result showed that the use of the combination of CMC and Arabic Gum stabilizer gave a significant effect on the overrun value, melting power, total dissolved solids, moisture content, dietary fiber, taste, texture and overalls. Moreover, there were no significant effect on color and flavor of the soursop velva. The experiment showed that soursop velva F4 (3:1) was the best formula with overrun value 9.93%, the melting power was 22 minutes 52 seconds, the total dissolved solids 19,10°Brix, the moisture content 71.508%, dietary fiber 3.301% and it has sensory values of color, taste, flavor, texture, overall at 3.66, 3.267, 3.33, 4.06, 3.10 respectively.

Generalization of the disruptive effects of alternative stimuli when combined with target stimuli in extinction.

PubMed

Podlesnik, Christopher A; Miranda-Dukoski, Ludmila; Jonas Chan, C K; Bland, Vikki J; Bai, John Y H

2017-09-01

Differential-reinforcement treatments reduce target problem behavior in the short term but at the expense of making it more persistent long term. Basic and translational research based on behavioral momentum theory suggests that combining features of stimuli governing an alternative response with the stimuli governing target responding could make target responding less persistent. However, changes to the alternative stimulus context when combining alternative and target stimuli could diminish the effectiveness of the alternative stimulus in reducing target responding. In an animal model with pigeons, the present study reinforced responding in the presence of target and alternative stimuli. When combining the alternative and target stimuli during extinction, we altered the alternative stimulus through changes in line orientation. We found that (1) combining alternative and target stimuli in extinction more effectively decreased target responding than presenting the target stimulus on its own; (2) combining these stimuli was more effective in decreasing target responding trained with lower reinforcement rates; and (3) changing the alternative stimulus reduced its effectiveness when it was combined with the target stimulus. Therefore, changing alternative stimuli (e.g., therapist, clinical setting) during behavioral treatments that combine alternative and target stimuli could reduce the effectiveness of those treatments in disrupting problem behavior. © 2017 Society for the Experimental Analysis of Behavior.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination

PubMed Central

2013-01-01

Background and purpose of the study The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Methods Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. Results The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. Conclusion It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness. PMID:23351568

Effects of albendazole combined with TSII-A (a Chinese herb compound) on optic neuritis caused by Angiostrongylus cantonensis in BALB/c mice.

PubMed

Feng, Feng; Feng, Ying; Liu, Zhen; Li, Wei-Hua; Wang, Wen-Cong; Wu, Zhong-Dao; Lv, Zhiyue

2015-11-25

Angiostrongylus cantonensis (A. cantonensis) infection can lead to optic neuritis, retinal inflammation, damage to ganglion cells, demyelination of optic nerve and visual impairment. Combined therapy of albendazole and dexamethasone is a common treatment for the disease in the clinic, but it plays no role in vision recovery. Therefore, it has been necessary to explore alternative therapies to treat this disease. Previous studies reported the neuro-productive effects of two constituents of Danshen (a Chinese herb)-tanshinone II-A (TSII-A) and cryptotanshinone (CPT), and this study aims to evaluate the impacts of TSII-A or CPT combined with albendazole on optic neuritis caused by A. cantonensis infection in a murine model. To assess the effects of TSII-A or CPT combined with albendazole on optic neuritis due to the infection, mice were divided into six groups, including the normal control group, infection group and four treatment groups (albendazole group, albendazole combined with dexamethasone group, albendazole combined with CPT group and albendazole combined with TSII-A group). The infection group and treatment groups were infected with A. cantonensis and the treatment groups received interventions from 14 dpi (days post infection), respectively. At 21 dpi, the visual acuity of mice in each group was examined by visual evoked potential (VEP). The pathologic alteration of the retina and optic nerve were observed by hematoxylin and eosin (H&E) staining and transmission electronic microscopy (TEM). Infection of A. cantonensis caused prolonged VEP latency, obvious inflammatory cell infiltration in the retina, damaged retinal ganglions and retinal swelling, followed by optic nerve fibre demyelination and a decreasing number of axons at 21 dpi. In treatment groups, albendazole could not alleviate the above symptoms; albendazole combined with dexamethasone lessened the inflammation of the retina, but was futile for the other changes; however, albendazole combined with CPT and albendazole combined with TSII-A showed obvious effects on the recovery of prolonged VEP latency, destruction and reduction of ganglion cells, optic nerve demyelination and axon loss. Compared with albendazole-CPT compound, albendazole combined with TSII-A was more effective. The current study demonstrates that albendazole combined with TSII-A plays a more effective role in treating optic neuritis caused by A. cantonensis in mice than with dexamethasone, as applied in conventional treatment, indicating that albendazole combined with TSII-A might be an alternate therapy for this parasitic disease in the clinic.

Combined use of Bacillus subtilis strain B-001 and bactericide for the control of tomato bacterial wilt.

PubMed

Peng, Di; Luo, Kun; Jiang, Huidan; Deng, Yanan; Bai, Lianyang; Zhou, Xiaomao

2017-06-01

Tomato bacterial wilt caused by Ralstonia solanacearum poses a serious threat to tomato production. However, no effective control measures are available. In this study, the bactericide Saisentong was combined with an effective biological control agent, Bacillus subtilis B-001, to control tomato bacterial wilt under greenhouse and field conditions. Growth of B-001 in vitro was unaffected by Saisentong. In greenhouse experiments, the combined application of B-001 and Saisentong via root irrigation or spray resulted in better disease control compared with either agent alone. In two field trials, at a Saisentong concentration of 400 or 500 mg kg -1 , the combined treatment was more effective than expected and showed a synergistic effect. A lower concentration of Saisentong (200 or 300 mg kg -1 ) in combination with B-001 resulted in an antagonistic effect. However, disease control was significantly greater compared with either treatment alone. The combination of Saisentong and B-001 effectively controls tomato bacterial wilt. The integrated strategy represents a promising new tool to control this disease. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

A study of cycle control, side effects and client's satisfaction of a low dose combined contraceptive containing ethinylestradiol/drospirenone (24/4 regimen).

PubMed

Chaiyasit, Noppadol; Taneepanichskul, Surasak

2010-05-01

To study cycle control, side effects, and satisfaction of low dose 24-day combined contraceptive containing 20 microg of Ethinylestradiol and 3 mg of Drospirenone. This was an open label, non-comparative study. The healthy females from the family planning clinic at King Chulalongkorn Memorial Hospital were assigned to receive six cycles of combined oral contraceptive containing 20 microg of ethinylestradiol and 3 mg of drospirenone administered daily for 24 days followed by 4-day hormone-free interval. Data were collected on cycle control, side effects, and satisfaction. Data were analyzed using descriptive statistics for descriptive data and Paired t test for comparison. One hundred fifty four women were assigned the study medication, including one (0.64%) who did not start medication. In the second reference period, the occurrence of frequent and infrequent bleeding was low (2.1% and 4.9%). Only one woman (0.65%) discontinued medication because of irregular bleeding. There was no pregnancy reported during the present study. Overall, the study medication was well tolerated and five subjects (3.24%) discontinued study because of side effects. No serious side effects related to the study medication were reported. The majority of women (84.2%) were satisfied and very satisfied with the treatment and most (73.3%) would continue the medication if it were available. The low dose combined contraceptive containing Ethinylestradiol/Drospirenone (24/4 regimen) has acceptable cycle control and good tolerability.

Supra-additive effects of tramadol and acetaminophen in a human pain model.

PubMed

Filitz, Jörg; Ihmsen, Harald; Günther, Werner; Tröster, Andreas; Schwilden, Helmut; Schüttler, Jürgen; Koppert, Wolfgang

2008-06-01

The combination of analgesic drugs with different pharmacological properties may show better efficacy with less side effects. Aim of this study was to examine the analgesic and antihyperalgesic properties of the weak opioid tramadol and the non-opioid acetaminophen, alone as well as in combination, in an experimental pain model in humans. After approval of the local Ethics Committee, 17 healthy volunteers were enrolled in this double-blind and placebo-controlled study in a cross-over design. Transcutaneous electrical stimulation at high current densities (29.6+/-16.2 mA) induced spontaneous acute pain (NRS=6 of 10) and distinct areas of hyperalgesia for painful mechanical stimuli (pinprick-hyperalgesia). Pain intensities as well as the extent of the areas of hyperalgesia were assessed before, during and 150 min after a 15 min lasting intravenous infusion of acetaminophen (650 mg), tramadol (75 mg), a combination of both (325 mg acetaminophen and 37.5mg tramadol), or saline 0.9%. Tramadol led to a maximum pain reduction of 11.7+/-4.2% with negligible antihyperalgesic properties. In contrast, acetaminophen led to a similar pain reduction (9.8+/-4.4%), but a sustained antihyperalgesic effect (34.5+/-14.0% reduction of hyperalgesic area). The combination of both analgesics at half doses led to a supra-additive pain reduction of 15.2+/-5.7% and an enhanced antihyperalgesic effect (41.1+/-14.3% reduction of hyperalgesic areas) as compared to single administration of acetaminophen. Our study provides first results on interactions of tramadol and acetaminophen on experimental pain and hyperalgesia in humans. Pharmacodynamic modeling combined with the isobolographic technique showed supra-additive effects of the combination of acetaminophen and tramadol concerning both, analgesia and antihyperalgesia. The results might act as a rationale for combining both analgesics.

Amoxicillin-potassium clavulanate: a novel beta-lactamase inhibitor.

PubMed

Smith, B R; LeFrock, J L

1985-06-01

Potassium clavulanate is a novel beta-lactamase inhibitor, which, in combination, expands the spectrum of amoxicillin to include many amoxicillin-resistant organisms. Potassium clavulanate is excreted 30-50 percent unchanged renally and its plasma time-course parallels that of amoxicillin. Several studies suggest that an increased incidence of gastrointestinal side effects may occur with this combination. In the current oral formulation, its greatest utility may be in pediatric infections due to beta-lactamase-producing Haemophilus influenzae and B. cattarhalis. In adults, the combination has not been adequately studied against other effective antibiotics.

Effect of 2-Phenylethanol as Antifungal Agent and Common Antifungals (Amphotericin B, Fluconazole, and Itraconazole) on Candida Species Isolated from Chronic and Recurrent Cases of Candidal Vulvovaginitis.

PubMed

Majdabadi, Niloufar; Falahati, Mehraban; Heidarie-Kohan, Fariba; Farahyar, Shirin; Rahimi-Moghaddam, Parvaneh; Ashrafi-Khozani, Mahtab; Razavi, Tandis; Mohammadnejad, Sina

2018-04-01

The antifungal effects of 2-phenylethanol are clearly visible through its intervention in Candida morphogenesis. Chronic and recurrent vulvovaginitis, however, does not respond to this standard experimental therapy; therefore, the study presented in this article investigated the effect of common antifungal drugs (amphotericin B [AMB], fluconazole [FLU], and itraconazole [ITC]), in combination with 2-phenylethanol, on the Candida species isolated from cases of chronic and recurrent vulvovaginitis, thereby allowing the recommendation of a more appropriate treatment option. Forty isolates from patients with chronic and recurrent vaginal candidiasis were investigated in this experimental study. The specimens were examined by direct microscopy, culturing, and PCR to identify the species. The antifungal effects of 2-phenylethanol and conventional drugs, both alone and in combination, were determined in duplicate. Finally, the findings were analyzed. In this study, 40 strains of Candida species were identified, whose agents were Candida albicans (95%) and Candida africana (5%). After 48 h, the minimum inhibitory concentration (MIC) range of the 2-phenylethanol was 800-3,200 μg/mL. Also, in the final study on the MIC levels of common antifungal drugs, AMB (0.42 μg/mL) had the lowest MIC, FLU (40.51 μg/mL) had the highest MIC, and the combination of ITC and 2-phenylethanol had the lowest fractional inhibitory concentration index (FICI) of any of the combinations (FICI range, 0.26-1.03). Combining FLU and ITC with 2-phenylethanol can effectively increase their antifungal effect.

The Effects of Teacher Directed Writing Instruction Combined with SOLO Literacy Suite

ERIC Educational Resources Information Center

Park, Y.; Ambrose, G.; Coleman, M. B.; Moore, T. C.

2017-01-01

The purpose of this study was to examine the effectiveness of an intervention in which teacher-led instruction was combined with computerized writing software to improve paragraph writing for three middle school students with intellectual disability. A multiple probe across participants design was used to evaluate the effectiveness of the…

Studies of the Effects of Perfluorocarbon Emulsions on Platelet Number and Function in Models of Critical Battlefield Injury

DTIC Science & Technology

2015-01-01

Year three: Using the ovine polytrauma model of combined hemorrhagic shock and blast TBI to test the effect of PFC intravenous infusion on platelet...could not be reassembled until late October. The schedule for testing and developing a sheep polytrauma model which combines blast injury with...This research project going forward is to assess PFC’s effect on platelet number and function in sheep 9 10 polytrauma model which combined blast

Efficacy of anti-IL-23 monotherapy versus combination therapy with anti-IL-17 in estrogen deficiency induced bone loss conditions.

PubMed

Shukla, Priyanka; Mansoori, Mohd Nizam; Singh, Divya

2018-05-01

Recent studies have identified that Interleukin (IL)-23/IL-17 axis plays crucial role in pathogenesis of inflammation and bone destruction. IL-23 is thought to promote joint destruction in arthritis by stimulating Th17 cells. IL-23 directly mediates bone loss by inducing osteoclastogenesis and receptor activator of kappa B ligand (RANKL) expression in T cells. IL-23 also promotes tartrate-resistant acid phosphatase (TRAP) activity of osteoclast in osteoblast-osteoclast co-culture. The role of IL-23 has not been studied in estrogen deficiency induced bone loss. Here, we study the effect of IL-23 neutralization in ovariectomized (Ovx) estrogen deficient mice on various immune and skeletal parameters. We also determine whether the combination of anti-IL-23 and anti-IL17 has enhanced osteoprotective effects compared to monotherapies. Treatment of anti-IL-23 and its combination with anti-IL-17 suppressed Th17 cell differentiation and promoted development of T regulatory cells. Anti-IL-23 and its combination with anti-IL-17 prevented bone loss. However, the individual monotherapies of anti-IL-23 and anti-IL-17 were more effective than combination therapy. Treatment of IL-17 and IL-23 cytokines to bone marrow stromal cells led to increased differentiation towards osteoblast lineage. Double neutralization of IL-23 and IL-17 might be inhibiting this phenomenon thus producing less potent effects. Our studies thus support bone protective effects of anti-IL-23 and that the monotherapies of neutralizing antibodies against IL-17 and IL-23 may be a more accepted mode of treatment in management of post-menopausal bone loss rather than combination therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Statistical approaches to assessing single and multiple outcome measures in dry eye therapy and diagnosis.

PubMed

Tomlinson, Alan; Hair, Mario; McFadyen, Angus

2013-10-01

Dry eye is a multifactorial disease which would require a broad spectrum of test measures in the monitoring of its treatment and diagnosis. However, studies have typically reported improvements in individual measures with treatment. Alternative approaches involve multiple, combined outcomes being assessed by different statistical analyses. In order to assess the effect of various statistical approaches to the use of single and combined test measures in dry eye, this review reanalyzed measures from two previous studies (osmolarity, evaporation, tear turnover rate, and lipid film quality). These analyses assessed the measures as single variables within groups, pre- and post-intervention with a lubricant supplement, by creating combinations of these variables and by validating these combinations with the combined sample of data from all groups of dry eye subjects. The effectiveness of single measures and combinations in diagnosis of dry eye was also considered. Copyright © 2013. Published by Elsevier Inc.

Abdominal Obesity and Risk of Hip Fracture: A Systematic Review and Meta-Analysis of Prospective Studies.

PubMed

Sadeghi, Omid; Saneei, Parvaneh; Nasiri, Morteza; Larijani, Bagher; Esmaillzadeh, Ahmad

2017-09-01

Data on the association between general obesity and hip fracture were summarized in a 2013 meta-analysis; however, to our knowledge, no study has examined the association between abdominal obesity and the risk of hip fracture. The present systematic review and meta-analysis of prospective studies was undertaken to summarize the association between abdominal obesity and the risk of hip fracture. We searched online databases for relevant publications up to February 2017, using relevant keywords. In total, 14 studies were included in the systematic review and 9 studies, with a total sample size of 295,674 individuals (129,964 men and 165,703 women), were included in the meta-analysis. Participants were apparently healthy and aged ≥40 y. We found that abdominal obesity (defined by various waist-hip ratios) was positively associated with the risk of hip fracture (combined RR: 1.24, 95% CI: 1.05, 1.46, P = 0.01). Combining 8 effect sizes from 6 studies, we noted a marginally significant positive association between abdominal obesity (defined by various waist circumferences) and the risk of hip fracture (combined RR: 1.36; 95% CI: 0.97, 1.89, P = 0.07). This association became significant in a fixed-effects model (combined effect size: 1.40, 95% CI: 1.25, 1.58, P < 0.001). Based on 5 effect sizes, we found that a 0.1-U increase in the waist-hip ratio was associated with a 16% increase in the risk of hip fracture (combined RR: 1.16, 95% CI: 1.04, 1.29, P = 0.007), whereas a 10-cm increase in waist circumference was not significantly associated with a higher risk of hip fracture (combined RR: 1.13, 95% CI: 0.94, 1.36, P = 0.19). This association became significant, however, when we applied a fixed-effects model (combined effect size: 1.21, 95% CI: 1.15, 1.27, P < 0.001). We found that abdominal obesity was associated with a higher risk of hip fracture in 295,674 individuals. Further studies are needed to test whether there are associations between abdominal obesity and fractures at other bone sites. © 2017 American Society for Nutrition.

Evaluations and Comparisons of Treatment Effects Based on Best Combinations of Biomarkers with Applications to Biomedical Studies

PubMed Central

Chen, Xiwei; Yu, Jihnhee

2014-01-01

Abstract Many clinical and biomedical studies evaluate treatment effects based on multiple biomarkers that commonly consist of pre- and post-treatment measurements. Some biomarkers can show significant positive treatment effects, while other biomarkers can reflect no effects or even negative effects of the treatments, giving rise to a necessity to develop methodologies that may correctly and efficiently evaluate the treatment effects based on multiple biomarkers as a whole. In the setting of pre- and post-treatment measurements of multiple biomarkers, we propose to apply a receiver operating characteristic (ROC) curve methodology based on the best combination of biomarkers maximizing the area under the receiver operating characteristic curve (AUC)-type criterion among all possible linear combinations. In the particular case with independent pre- and post-treatment measurements, we show that the proposed method represents the well-known Su and Liu's (1993) result. Further, proceeding from derived best combinations of biomarkers' measurements, we propose an efficient technique via likelihood ratio tests to compare treatment effects. We show an extensive Monte Carlo study that confirms the superiority of the proposed test in comparison with treatment effects based on multiple biomarkers in a paired data setting. For practical applications, the proposed method is illustrated with a randomized trial of chlorhexidine gluconate on oral bacterial pathogens in mechanically ventilated patients as well as a treatment study for children with attention deficit-hyperactivity disorder and severe mood dysregulation. PMID:25019920

Combined use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina. Rationale, efficacy, and adverse effects.

PubMed

Strauss, W E; Parisi, A F

1988-10-01

During the past decade, the therapy for stable angina pectoris has greatly expanded with the introduction of the calcium-channel blockers. Initially studied as monotherapy, these agents have been regularly used in combination with other antianginal medications, most notably the beta-adrenergic blockers. Although there are pharmacologic rationales for combining these agents, in daily practice, the major impetus for combination therapy is continuing angina during monotherapy. At least one well-conducted double-blind study was done to confirm that diltiazem, verapamil, and nifedipine each can markedly improve both subjective and objective measures of efficacy when used in combination with a beta-blocker. However, individual patient responses are of chief importance. Many persons do better with monotherapy than with combination treatment. The offsetting hemodynamic effects of nifedipine and a beta-blocker generally work well together; however, minor side effects are not infrequent. In the patient with underlying conduction system disease, this combination is clearly preferable. Diltiazem with a beta-blocker is usually well-tolerated, with a low incidence of adverse effects, similar to the experience with diltiazem monotherapy. Verapamil in conjunction with a beta-blocker warrants the greatest concern; approximately 10% to 15% of patients will have significant bradycardia, heart block, hypotension, or congestive failure. When these agents are used concurrently, reduced dosages, especially of the beta-blocker, will likely result in a lower incidence of adverse effects with maintained efficacy.

Attenuation of insulin-resistance-based hepatocarcinogenesis and angiogenesis by combined treatment with branched-chain amino acids and angiotensin-converting enzyme inhibitor in obese diabetic rats.

PubMed

Yoshiji, Hitoshi; Noguchi, Ryuichi; Kaji, Kosuke; Ikenaka, Yasuhide; Shirai, Yusaku; Namisaki, Tadashi; Kitade, Mitsuteru; Tsujimoto, Tatsuhiro; Kawaratani, Hideto; Fukui, Hiroshi

2010-04-01

Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Because neovascularization plays an important role in HCC, including hepatocarcinogenesis, an angiostatic therapy would be a promising approach for chemoprevention against HCC. The aim of the present study was to examine the combined effect of clinically used branched-chain amino acids (BCAAs) and an angiotensin-converting enzyme inhibitor (ACE-I), in conjunction with neovascularization, on hepatocarcinogenesis under the condition of IR. The combined effect of the treatment on the development of liver enzyme-altered preneoplastic lesions, angiogenesis, and several indices was elucidated in obese diabetic rats. We also performed several sets of in vitro experiments to examine the mechanisms involved. When used individually, both BCAAs and ACE-I at clinically comparable low doses significantly attenuated the development of preneoplastic lesions, along with the suppression of both angiogenesis and vascular endothelial growth factor (VEGF) expression. The combination treatment with both agents exerted a more potent inhibitory effect than that of either single agent. Our in vitro study showed a similar combined effect on endothelial cell tubule formation. This combination regimen showed a marked chemopreventive effect against hepatocarcinogenesis, along with suppression of neovascularization and VEGF expression, in obese diabetic rats. Because both BCAAs and ACE-Is are widely used in clinical practice, this combination therapy may represent a potential new strategy for chemoprevention against IR-based HCC in the future.

Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells

PubMed Central

2010-01-01

Background Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. Methods The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. Results We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. Conclusions These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis. PMID:20804622

Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells.

PubMed

Yu, Ji Sun; Kim, An Keun

2010-08-24

Pigmentation in human skin is an important defense mechanism against sunlight or oxidative stress. Despite the protective role of melanin, abnormal hyperpigmentation such as freckles and chloasma sometimes can be serious aesthetic problems. Because of these effects of hyperpigmentation, people have considered the effect of depigmentation. Azelaic acid (AZ) is a saturated dicarboxylic acid found naturally in wheat, rye, and barley. Previously, we showed that AZ inhibited melanogenesis. In this study, we investigated the antimelanogenic activity of combination of AZ and taurine (Tau) in B16F10 mouse melanoma cells. The mouse melanoma cell line B16F10 was used in the study. We measured melanin contents and tyrosinase activity. To gain the change of protein expression, we carried out western blotting. We investigated that AZ combined with taurine (Tau) show more inhibitory effects in melanocytes than the treatment of AZ alone. AZ combined with Tau inhibited the melanin production and tyrosinase activity of B16F10 melanoma cells without significant cytotoxicity. Also inhibitory effects after treatment with these combined chemical are stronger than AZ alone on melanogenesis. These findings indicate that AZ with Tau might play an important role in the regulation of melanin formation and be useful as effective ingredients in antimelanogesis.

Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm.

PubMed

Bai, Li-Yue; Dai, Hao; Xu, Qin; Junaid, Muhammad; Peng, Shao-Liang; Zhu, Xiaolei; Xiong, Yi; Wei, Dong-Qing

2018-02-05

Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

PubMed

Marostica, Lucas Lourenço; Silva, Izabella Thaís; Kratz, Jadel Müller; Persich, Lara; Geller, Fabiana Cristina; Lang, Karen Luise; Caro, Miguel Soriano Balparda; Durán, Fernando Javier; Schenkel, Eloir Paulo; Simões, Cláudia Maria Oliveira

2015-10-19

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

Bone marrow mesenchymal stem cells combined with minocycline improve spinal cord injury in a rat model

PubMed Central

Chen, Dayong; Zeng, Wei; Fu, Yunfeng; Gao, Meng; Lv, Guohua

2015-01-01

The aims of this study were to assess that the effects of bone marrow mesenchymal stem cells (BMSCs) combination with minocycline improve spinal cord injury (SCI) in rat model. In the present study, the Wistar rats were randomly divided into five groups: control group, SCI group, BMSCs group, Minocycline group and BMSCs + minocycline group. Basso, Beattie and Bresnahan (BBB) test and MPO activity were used to assess the effect of combination therapy on locomotion and neutrophil infiltration. Inflammation factors, VEGF and BDNF expression, caspase-3 activation, phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions were estimated using commercial kits or western blot, respectively. BBB scores were significantly increased and MPO activity was significantly undermined by combination therapy. In addition, combination therapy significantly decreased inflammation factors in SCI rats. Results from western blot showed that combination therapy significantly up-regulated the protein of VEGF and BDNF expression and down-regulated the protein of phosphorylation-p38MAPK, proNGF, p75NTR and RhoA expressions in SCI rats. Combination therapy stimulation also suppressed the caspase-3 activation in SCI rats. These results demonstrated that the effects of bone marrow mesenchymal stem cells combination with minocycline improve SCI in rat model. PMID:26722382

Investigating Aerobic, Anaerobic Combine Technical Trainings' Effects on Performance in Tennis Players

ERIC Educational Resources Information Center

Suna, Gürhan; Kumartasli, Mehmet

2017-01-01

The aim of this study is to investigate eight-week aerobic, anaerobic combine technical trainings' effects on developments of performance. 21 athletes of tennis proficiency students from Sports Sciences Department were joined to the study voluntarily. Participated in the research athletes' ages' mean was 22,2 ± 0,3 year, lengths' mean was 177,3 ±…

Effect of the Written and Combined Warnings on the Cigarette Pockets on University Students

ERIC Educational Resources Information Center

Gercek, Cem; Dogan, Nuri

2012-01-01

The general aim of this study is to analyze the effects of the written and combined (written and pictures) warning statements on the cigarette pockets on university students. The sample of the study includes a total of 231 undergraduate students. The participants were divided into two groups: the first group was presented only written warnings,…

Parent Involvement in CBT Treatment of Adolescent Depression: Experiences in the Treatment for Adolescents with Depression Study (TADS)

ERIC Educational Resources Information Center

Wells, Karen C.; Albano, Anne Marie

2005-01-01

The Treatment for Adolescents With Depression Study (TADS) evaluated the short- and long-term effectiveness of cognitive behavior therapy (CBT) alone, fluoxetine alone, and their combination, relative to pill placebo, and the 12-week treatment effects were recently published (TADS Team, 2004). Results showed that treatment that combined CBT with…

Pathways to prevention: protocol for the CAP (Climate and Preventure) study to evaluate the long-term effectiveness of school-based universal, selective and combined alcohol misuse prevention into early adulthood.

PubMed

Newton, Nicola C; Stapinski, Lexine; Slade, Tim; Champion, Katrina E; Barrett, Emma L; Chapman, Catherine; Smout, Anna; Lawler, Siobhan; Mather, Marius; Castellanos-Ryan, Natalie; Conrod, Patricia J; Teesson, Maree

2018-05-21

Alcohol use and associated harms are among the leading causes of burden of disease among young people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition from adolescence into early adulthood. A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior, and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an intention-to-treat framework. This study will provide the first ever evaluation of the long-term effectiveness of combining universal and selective approaches to alcohol prevention and will examine the durability of intervention effects into the longer-term, over a 7-year period from adolescence to early adulthood. This trial was registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12612000026820 ) on January 6th 2012.

Effect of Aloe vera topical gel combined with tretinoin in treatment of mild and moderate acne vulgaris: a randomized, double-blind, prospective trial.

PubMed

Hajheydari, Zohreh; Saeedi, Majid; Morteza-Semnani, Katayoun; Soltani, Aida

2014-04-01

Topical retinoids are considered first-line therapy in the treatment of acne vulgaris, yet can be associated with cutaneous irritations. Combination therapy with natural preparations could be effective in treatment and decreasing adverse events. The aim of this study was to compare the efficacy and safety of the combination of tretinoin (TR) cream (0.05%) and Aloe vera topical gel (50%) with TR and vehicle. The randomized, double-blind, prospective 8-week trial evaluated inflammatory and non-inflammatory lesion scores and tolerability in 60 subjects with mild to moderate acne vulgaris (global acne grading system scale). Several formulations of A. vera leaf gel were prepared and the most stable one was selected for clinical study based on physicochemical evaluations. The combination therapy showed superior efficacy to TR and placebo. TR/Aloe vera gel (AVG) was significantly more effective in reducing non-inflammatory (p = 0.001), inflammatory (p = 0.011) and total (p = 0.003) lesion scores than control group. The highest percentage of adverse cutaneous effect was reported for scaling. At the end of study, erythema in the TR/AVG-treated group was significantly less severe (p = 0.046). The combination TR/AVG was well tolerated and significantly more effective than TR and vehicle for the treatment of mild to moderate acne vulgaris.

Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

PubMed

Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

2016-09-01

Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chemotherapy in combination with cytokine-induced killer cell transfusion: An effective therapeutic option for patients with extensive stage small cell lung cancer.

PubMed

Huang, Jianmin; Kan, Quancheng; Lan; Zhao, Xuan; Zhang, Zhen; Yang, Shuangning; Li, Hong; Wang, Liping; Xu, Li; Cheng, Zhe; Zhang, Yi

2017-05-01

In the past decade of clinical studies, the combination of chemotherapy with cytokine induced killer (CIK) cell transfusion has confirmed a promised efficacy in several types of cancer. CIK cells are a mixture of T lymphocytes, generated from peripheral blood mononuclear cells induced by multiple cytokines. This study was aimed to evaluate the clinical efficacy of chemotherapy combined with CIK- cell therapy in patients with extensive stage small cell lung cancer (ES SCLC). Forty four patients with ES SCLC were enrolled in this study. All the patients received treatment from Oct 2010 to Sep 2013 in the First Affiliated Hospital of Zhengzhou University. Included patients were equally divided into 2 groups according to the treatment strategies. Patients in the combined treatment group received chemotherapy combined with CIK-cell transfusion and patients in the control group received chemotherapy alone. The short-term effects, overall survival (OS), progress free survival (PFS) and therapy-related adverse events were analyzed retrospectively. Short-term efficacy evaluation indicated that the total response rates in the combined treatment group and control group were 40.9% (9/22) and 9.1% (2/22), respectively. There was a significant difference between the two groups (p=0.0339). Furthermore, the PFS of the combined treatment group was significantly longer than that of the control group (8 vs. 4months, P=0.005). No severe side effect was observed after transfusion of CIK cells. These results indicated that chemotherapy combined with CIK-cell immunotherapy might provide a safe and effective treatment for patients with ES SCLC. Copyright © 2016. Published by Elsevier B.V.

Effects of etoposide alone and in combination with piroxicam on canine osteosarcoma cell lines.

PubMed

Ong, S M; Saeki, K; Tanaka, Y; Nishimura, R; Nakagawa, T

2016-12-01

Osteosarcoma (OSA) is the most common primary bone tumour in dogs. The poor survival rate in dogs with OSA highlights the need for new therapeutic approaches. This study evaluated the cytotoxic effects of etoposide, alone and in combination with piroxicam, on canine OSA cell cultures. Etoposide alone significantly suppressed cell growth and viability, whereas etoposide in combination with piroxicam exhibited concentration dependent cytotoxicity. The anti-proliferative effect was a result of inactivity of the Cdc2-cyclin B1 complex, which correlated with an increase in the G 2 /M fraction. This subsequently activated the apoptosis cascade, as indicated by elevated apoptosis levels and up-regulation of poly (ADP-ribose) polymerase proteolytic cleavage. Down-regulation of survivin expression induced by the combination treatment may have contributed to the enhanced cytotoxicity. The results of this study suggest that further investigation of etoposide and piroxicam as a therapeutic combination for canine OSA is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Antioxidative Effect of Chamomile, Anthocyanoside and their Combination on Bleomycin-induced Pulmonary Fibrosis in Rat.

PubMed

Javadi, Iraj; Emami, SeyedAlireza

2015-08-01

Bleomycin is a small peptide with 1500Daltun of molecular weight which has two junction areas in two molecule's opposite sides, one of them to relate to the DNA and the other to relate to the iron. Iron is a crucially important factor in free radical production and cytotoxic activity of bleomycin. The study attempts to study, and compare, the effect of using Chamomile, Anthocyanoside and their combination, as anti-inflammatory agent to ameliorates, to prevent or control the development of fibrosis due to Bleomycin (BLM). to prepare pulmonary fibrosis model, male Wistar rats weighting 180-220g were assigned to specific groups Rats of each group received intratracheally 1U/100 g of BLM. 20 rats were divided to five comparable groups, as(1) BLM group, (2) saline group, (3) Chamomile group, (4) Anthocyanoside group, (5) combination of Anthocyanoside and Chamomile group. Antioxidative combinations were given as pretreatment and treatment after the rats received Bleomycine. After 3 week, Malondialdehyde (MDA)was measured for each rat's lung. After three weeks, MDA was reduced, compared to BLM group, to 44.27%, 37.80% and 46.07% in Anthocyanoside, Chamomiland combination group, respectively. It was concluded from the present study that administration of combination of Chamomile and Anthocyanoside lead to a significant reduction in Bleomycin-induced MDA. The mechanism of the effect of these combinations is possibly the result of phenolic combinations as antioxidant and oxy free radical scavenger and inhibitor of lipid peroxidation.

Inhibitory effects of Silibinin combined with doxorubicin in hepatocellular carcinoma; an in vivo study.

PubMed

Li, Wei-Guo; Wang, He-Qun

2016-01-01

Hepatocellular carcinoma (HCC) is the one of the most common cancers and the third leading cause of cancer related mortality in the world. Unacceptable side effect and development of treatment resistance are the major concerns with the conventional chemotherapeutic agents. Combination therapy using phytotherapeutic agents is attracting the attention of investigators in view of the current needs. In the present study we have evaluated the synergistic effect of silibinin, a nontoxic phytotherapeutic agent in combination with doxorubicin, in advanced HCC using HEPG2 cells and an orthotopic rat model of HCC. The results showed that silibinin strongly synergized with doxorubicin-induced growth inhibition, G2-M arrest, and apoptosis of HEPG2 cells. Silibinin-doxorubicin combination also inhibited cdc2/p34 kinase activity when histone H1 was used as substrate. The combination regimen also moderately increased the expression of cdc25C-cyclin B1-cdc2/p34 associated upstream kinases (Chk1). Simultaneous treatment with silibinin-doxorubicin combination showed a 41% increase in the apoptotic cell death (p=0.01), which was 3-fold higher than what was observed with silibinin or doxorubicin individually. In the orthotopic rat model treatment with silibinin-doxorubicin reduced tumor growth by close to 30% at nearly twice lower dose of individual drugs in the combination group. Our study suggests that combination therapy using silibinin-doxorubicin may show a better therapeutic efficacy in patients with HCC. These findings need to be further validated in human clinical trials.

The effect of combined mechanism ankle support on postural control of patients with chronic ankle instability.

PubMed

Hadadi, Mohammad; Ebrahimi, Ismaeil; Mousavi, Mohammad Ebrahim; Aminian, Gholamreza; Esteki, Ali; Rahgozar, Mehdi

2017-02-01

Chronic ankle instability is associated with neuromechanical changes and poor postural stability. Despite variety of mechanisms of foot and ankle orthoses, almost none apply comprehensive mechanisms to improve postural control in all subgroups of chronic ankle instability patients. The purpose of this study was to investigate the effect of an ankle support implementing combined mechanisms to improve postural control in chronic ankle instability patients. Cross-sectional study. An ankle support with combined mechanism was designed based on most effective action mechanisms of foot and ankle orthoses. The effect of this orthosis on postural control was evaluated in 20 participants with chronic ankle instability and 20 matched healthy participants. The single-limb stance balance test was measured in both groups with and without the new orthosis using a force platform. The results showed that application of combined mechanism ankle support significantly improved all postural sway parameters in chronic ankle instability patients. There were no differences in means of investigated parameters with and without the orthosis in the healthy group. No statistically significant differences were found in postural sway between chronic ankle instability patients and healthy participants after applying the combined mechanism ankle support. The combined mechanism ankle support is effective in improving static postural control of chronic ankle instability patients to close to the postural sway of healthy individual. the orthosis had no adverse effects on balance performance of healthy individuals. Clinical relevance Application of the combined mechanism ankle support for patients with chronic ankle instability is effective in improving static balance. This may be helpful in reduction of recurrence of ankle sprain although further research about dynamic conditions is needed.

The renal effects of droxidopa are maintained in propranolol treated cirrhotic rats.

PubMed

Rodríguez, Sarai; Raurell, Imma; Ezkurdia, Nahia; Augustin, Salvador; Esteban, Rafael; Genescà, Joan; Martell, María

2015-02-01

Droxidopa improves hemodynamic and renal alterations of cirrhotic rats without changing portal pressure. We aimed to evaluate the effects of a combined treatment with droxidopa and non-selective beta-blockers or statins in order to decrease portal pressure, while maintaining droxidopa beneficial effects. Acute studies combining droxidopa with carvedilol, propranolol or atorvastatin in four-week bile-duct ligated (BDL) rats and a chronic study combining propranolol and droxidopa for 5 days in CCl4 -cirrhotic rats were performed. Hemodynamic values were registered and biochemical parameters from blood and urine samples analyzed. Bile-duct ligated rats treated with carvedilol + droxidopa showed no changes in mean arterial pressure (MAP) and portal pressure (PP) compared to vehicles. Atorvastatin + droxidopa combination also failed to reduce PP, but maintained the beneficial increase in MAP and superior mesenteric artery resistance (SMAR) and decrease in blood flow (SMABF) caused by droxidopa. In contrast, the acute administration of propranolol + droxidopa significantly reduced PP maintaining a mild increase in MAP and improving, in an additive way, the decrease in SMABF and increase in SMAR caused by droxidopa. This combination also preserved droxidopa diuretic effect. When chronically administered to CCl4 -cirrhotic rats, propranolol + droxidopa caused a decrease in PP, a significant reduction in SMABF and an increase in SMAR. The combination did not alter liver function and droxidopa diuretic and natriuretic effect, and even improved free water clearance. Droxidopa could be effective for the renal alterations of cirrhotic patients on propranolol therapy and the combination of both drugs may balance the adverse effects of each treatment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low-dose prazosin alone and in combination with propranolol or naltrexone: effects on ethanol and sucrose seeking and self-administration in the P rat.

PubMed

Verplaetse, Terril L; Czachowski, Cristine L

2015-08-01

Evidence suggests that the noradrenergic system mediates ethanol reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer seeking and self-administration. Male alcohol-preferring (P) rats (n = 20/experiment) were trained to complete a response requirement (RR) resulting in access to 1 % sucrose (n = 10) or 10 % ethanol (n = 10) for 20 min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, and 1.0 mg/kg, intraperitoneally (IP)), or prazosin in combination with propranolol (5 mg/kg (IP); Exp. 1) or in combination with naltrexone (0.03 mg/kg, subcutaneously (SC); Exp. 2). For Exp. 1, prazosin alone effectively decreased sucrose seeking more than ethanol seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol seeking more than sucrose seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp. 2, prazosin alone and naltrexone alone were effective in decreasing ethanol seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol seeking and consumption and sucrose intake, but not sucrose seeking. Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone and also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers.

Low-Dose Prazosin Alone and in Combination with Propranolol or Naltrexone: Effects on Ethanol- and Sucrose-Seeking and Self-Administration in the P Rat

PubMed Central

Verplaetse, Terril L.; Czachowski, Cristine L.

2015-01-01

Rationale Evidence suggests that the noradrenergic system mediates ethanol-reinforcement. However, preclinical studies suggest that noradrenergic antagonists block other oral reinforcers indicating possible unwanted secondary medication effects. Methods This study examined combinations of low-dose prazosin with propranolol or naltrexone using a behavioral paradigm that separately assesses reinforcer-seeking and self-administration. Male alcohol-preferring (P) rats (n=20/experiment) were trained to complete a response requirement (RR) resulting in access to 1% sucrose (n=10) or 10% ethanol (n=10) for 20min. Rats received vehicle, prazosin alone (0.125, 0.25, 0.5, 1.0 mg/kg; intraperitoneally (IP)) or prazosin in combination with propranolol (5 mg/kg (IP); Exp1) or in combination with naltrexone (0.03 mg/kg (subcutaneously (SC); Exp2). Results For Exp1, prazosin alone effectively decreased sucrose-seeking more than ethanol-seeking, but decreased ethanol self-administration only. Propranolol alone effectively decreased ethanol-seeking more than sucrose-seeking and decreased ethanol intake only. At some dose combinations, there was a greater attenuation of ethanol and sucrose intake relative to either drug alone. For Exp2, prazosin alone and naltrexone alone were effective in decreasing ethanol-seeking and intake only. Combination treatment was more effective than either drug alone at decreasing ethanol-seeking and consumption and sucrose intake, but not sucrose-seeking. Conclusions Propranolol and naltrexone alone were specific to ethanol indicating that low doses of either medication may be beneficial in treating alcohol use disorders. Prazosin in combination with propranolol or naltrexone was more effective than either drug alone, but also reduced sucrose-reinforced behaviors. These data suggest that the noradrenergic system is a viable target for developing treatment approaches for problem drinkers. PMID:25743758

Effects of a workplace-smoking ban in combination with tax increases on smoking in the Dutch population.

PubMed

Verdonk-Kleinjan, Wendy M I; Candel, Math J J M; Knibbe, Ronald A; Willemsen, Marc C; de Vries, Hein

2011-06-01

In the Netherlands, between 2003 and 2005, 3 tobacco control measures were implemented: a workplace-smoking ban and 2 tax increases on tobacco products. This study explores how the combination of measures influences the smoking behavior of the general population divided into subpopulations with and without paid work (all aged 16-65 years). Data from the Dutch Continuous Survey of Smoking Habits were used. The total sample consisted of 32,014 respondents (27,150 with paid work and 4,864 without paid work) aged 16-65 years. Analyses were done by linear and logistic regression, controlling for relevant factors. For respondents with paid work, the combination of a smoking ban and 2 tax increases led to a decrease in the number of cigarettes per day and in the prevalence of daily smoking. For respondents without paid work, there was no significant effect on any of the outcome parameters. In both groups, there was no evidence that the effect of the measures on smoking was moderated by the respondent's gender, age, or level of education. The combination of policy measures has influenced the smoking behavior of respondents with paid work in a positive way. Compared with most other studies, the effect of the workplace-smoking ban alone is smaller. However, the effect of the combined interventions is higher than the that of tax increases in other studies. Among respondents without paid work who were exposed to tax increases only, no significant effects were found.

Can the Medical-nursing Combined Care Promote the Accessibility of Health Services for the Elderly in Nursing Home? A Study Protocol of Analysis of the Effectiveness Regarding Health Service Utilization, Health Status and Satisfaction with Care

PubMed Central

Bao, J; Wang, X-J; Yang, Y; Dong, R-Q; Mao, Z-F

2015-01-01

ABSTRACT Background: Currently, segmentation of healthcare and daily care for the elderly living in nursing homes usually results in the elderly not getting medical treatment timely and effectively. The medical-nursing combined care, which has been put into practice in several areas in China, is developed to enhance the accessibility of healthcare for the elderly. The aim of the study is to explore the effectiveness of the new care service, based on Andersen model, regarding health service utilization, health status and service satisfaction. Methods: The effectiveness of medical-nursing combined care will be measured in a cross-sectional study in nine nursing homes in Jianghan District, Wuhan, China, with 1067 old residents expected to participate. The questionnaire containing items of demographics, health service use, service satisfaction and instrument of SF-36 V2 is developed based on the conceptual framework of Andersen behaviour model of health service utilization. Descriptive analysis, variance analysis, multiple factors analysis, and correlation analysis will be performed to compare the sociological characteristics, health service use, health status and service satisfaction of the elderly living in different modes of nursing homes, to explore the influence factors of care effectiveness, as well as to study the relationship between health behaviour and health outcomes. Conclusion: The study design of analysing the effects of medical-nursing combined care and performing the horizontal comparison among the nursing homes under the framework of Andersen model is blazing new trails. Recruitment and design of questionnaire are important issues. Successful data collection and quality control are also necessary. Taking these into account, this study is estimated to provide evidence for the effectiveness of medical-nursing combined care service in China. PMID:27398940

Effects of Combined Transplantation of Multipotent Mesenchymal Stromal and Hemopoietic Stem Cells on Regeneration of the Hemopoietic Tissue.

PubMed

Maklakova, I Yu; Grebnev, D Yu

2017-05-01

The effect of allogenic combined transplantation of placental multipotent mesenchymal stromal and hemopoietic stem cells on regeneration of the myeloid tissue and spleen after acute blood loss was studied in laboratory mice. Combined transplantation of these cells did not change the content of cytogenetically modified cells in the bone marrow under normal conditions, but reduced their levels after acute blood loss. Combined transplantation of multipotent mesenchymal stromal and hemopoietic stem cells promoted activation of erythropoiesis and granulocytopoiesis. The major morphometric and cytological parameters of the white pulp of the spleen decreased, presumably due to immunosuppressive effect of multipotent mesenchymal stromal cells.

Efficacy and Safety of Indigo Naturalis in Combination with Narrow-Band Ultraviolet B for Treatment of Pityriasis Rosea: A Meta-Analysis

PubMed Central

Xue, Y. N.; Li, Z. W.; Zhang, W.; Ji, X. P.; Fan, Z.

2018-01-01

Pityriasis rosea (PR), a skin rash, causes substantial discomfort in patients. There is a lack of effective therapies for PR. A combination of ultraviolet irradiation and indigo naturalis treatment has been shown to be a safe and effective regime for control of PR; however, the data have been largely inconsistent. Tis meta-analysis further evaluated the efficacy and safety of this combination in patients with PR. The PubMed, Embase, Cochrane Library, CNKI, VIP, and Wan Fang databases were searched for relevant RCTs of this combination therapy in patients with PR. A total of eight studies with a combined study population of 688 patients published between January 2006 and March 2016 were eligible for this meta-analysis. The RevMan 5.3 software was used for the meta-analysis. The regimen of compound indigo naturalis plus NB-UVB showed much better control of PR as compared to that achieved with use of compound indigo naturalis or NB-UVB alone in terms of cure rate or effective rate. However, no significant difference was observed between the two with respect to incidence of adverse effects. The analysis was affected by publication bias as revealed by funnel plot analysis. Further studies with large sample sizes are required to confirm our findings. PMID:29770152

Efficacy and Safety of Indigo Naturalis in Combination with Narrow-Band Ultraviolet B for Treatment of Pityriasis Rosea: A Meta-Analysis.

PubMed

Wang, L; Xue, Y N; Li, Z W; Zhang, W; Ji, X P; Fan, Z; Li, Y J

2018-01-01

Pityriasis rosea (PR), a skin rash, causes substantial discomfort in patients. There is a lack of effective therapies for PR. A combination of ultraviolet irradiation and indigo naturalis treatment has been shown to be a safe and effective regime for control of PR; however, the data have been largely inconsistent. Tis meta-analysis further evaluated the efficacy and safety of this combination in patients with PR. The PubMed, Embase, Cochrane Library, CNKI, VIP, and Wan Fang databases were searched for relevant RCTs of this combination therapy in patients with PR. A total of eight studies with a combined study population of 688 patients published between January 2006 and March 2016 were eligible for this meta-analysis. The RevMan 5.3 software was used for the meta-analysis. The regimen of compound indigo naturalis plus NB-UVB showed much better control of PR as compared to that achieved with use of compound indigo naturalis or NB-UVB alone in terms of cure rate or effective rate. However, no significant difference was observed between the two with respect to incidence of adverse effects. The analysis was affected by publication bias as revealed by funnel plot analysis. Further studies with large sample sizes are required to confirm our findings.

Triple combination antibiotic therapy for carbapenemase-producing Klebsiella pneumoniae: a systematic review.

PubMed

Jacobs, David M; Safir, M Courtney; Huang, Dennis; Minhaj, Faisal; Parker, Adam; Rao, Gauri G

2017-11-25

The spread of carbapenemase-producing K. pneumoniae (CPKP) has become a significant problem worldwide. Combination therapy for CPKP is encouraging, but polymyxin resistance to many antibiotics is hampering effective treatment. Combination therapy with three or more antibiotics is being increasingly reported, therefore we performed a systematic review of triple combination cases in an effort to evaluate their clinical effectiveness for CPKP infections. The PubMed database was searched to identify all published clinical outcomes of CPKP infections treated with triple combination therapy. Articles were stratified into two tiers depending on the level of clinical detail provided. A tier 1 study included: antibiotic regimen, regimen-specific outcome, patient status at onset of infection, and source of infection. Articles not reaching these criteria were considered tier 2. Thirty-three studies were eligible, 23 tier 1 and ten tier 2. Among tier 1 studies, 53 cases were included in this analysis. The most common infection was pneumonia (31%) followed by primary or catheter-related bacteremia (21%) and urinary tract infection (17%). Different combinations of antibiotic classes were utilized in triple combinations, the most common being a polymyxin (colistin or polymyxin B, 86.8%), tigecycline (73.6%), aminoglycoside (43.4%), or carbapenem (43.4%). Clinical and microbiological failure occurred in 14/39 patients (35.9%) and 22/42 patients (52.4%), respectively. Overall mortality for patients treated with triple combination therapy was 35.8% (19/53 patients). Triple combination therapy is being considered as a treatment option for CPKP. Polymyxin-based therapy is the backbone antibiotic in these regimens, but its effectiveness needs establishing in prospective clinical trials.

Design and characterization of diclofenac diethylamine transdermal patch using silicone and acrylic adhesives combination.

PubMed

Panchaxari, Dandigi M; Pampana, Sowjanya; Pal, Tapas; Devabhaktuni, Bhavana; Aravapalli, Anil Kumar

2013-01-07

The objective of the study was to develop and characterize Diclofenac Diethylamine (DDEA) transdermal patch using Silicone and acrylic adhesives combination. Modified solvent evaporation method was employed for casting of film over Fluoropolymer coated polyester release liner. Initial studies included solubilization of drug in the polymers using solubilizers. The formulations with combination of adhesives were attempted to combine the desirable features of both the adhesives. The effect of the permeation enhancers on the drug permeation were studied using pig ear skin. All the optimized patches were subjected to adhesion, dissolution and stability studies. A 7-day skin irritancy test on albino rabbits and an in vivo anti-inflammatory study on wistar rats by carrageenan induced paw edema method were also performed. The results indicated the high percent drug permeation (% CDP-23.582) and low solubility nature (1%) of Silicone adhesive and high solubility (20%) and low% CDP (10.72%) of acrylic adhesive. The combination of adhesives showed desirable characteristics for DDEA permeation with adequate % CDP and sufficient solubility. Release profiles were found to be dependent on proportion of polymer and type of permeation enhancer. The anti-inflammatory study revealed the sustaining effect and high percentage inhibition of edema of C4/OLA (99.68%). The acute skin irritancy studies advocated the non-irritant nature of the adhesives used. It was concluded that an ideal of combination of adhesives would serve as the best choice, for fabrication of DDEA patches, for sustained effect of DDEA with better enhancement in permeation characteristics and robustness.

Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

PubMed

Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

2017-10-01

Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined Cognitive and Parent Training Interventions for Adolescents with ADHD and Their Mothers: A Randomized Controlled Trial

PubMed Central

Steeger, Christine M.; Gondoli, Dawn M.; Gibson, Bradley S.; Morrissey, Rebecca A.

2015-01-01

Objective This study examined the individual and combined effects of two non-pharmacological treatments for Attention-Deficit/Hyperactivity Disorder (ADHD): Cogmed working memory training (CWMT) for adolescents, and behavioral parent training (BPT) for mothers. Method Ninety-one adolescents (ages 11–15) and their mothers were randomized to one of four CWMT and BPT treatment and active control (placebo) group combinations of 5-week interventions. At pre- and post-test, mothers and teachers completed rating forms, and adolescents completed neuropsychological measures of working memory (WM). Results Individual intervention effects showed that treatment CWMT significantly improved WM spans, whereas there were no significant differences for treatment or control BPT on reports of parenting-related outcomes. Combined treatment effects indicated an overall pattern of greatest improvements for the control CWMT/treatment BPT group, as compared to the other three groups, on adolescent WM deficit, behavioral regulation problems, and global executive deficit. Most significant effects for outcomes were main effects of improvements over time. Conclusions: Combination CWMT and BPT did not result in increased treatment gains. However, potential effects of combined treatment may have been masked by greater perceived benefits arising from lack of struggle in the non-adaptive, CWMT active control condition. Future combined intervention research should focus on specific, theoretically-driven WM deficits among individuals with ADHD, include possible adaptations to the standard CWMT program, examine effectiveness of cognitive treatments combined with contextual interventions, and utilize appropriate control groups to fully understand the unique and combined effects of interventions. PMID:25731907

Combinations of techniques that effectively change health behavior: evidence from Meta-CART analysis.

PubMed

Dusseldorp, Elise; van Genugten, Lenneke; van Buuren, Stef; Verheijden, Marieke W; van Empelen, Pepijn

2014-12-01

Many health-promoting interventions combine multiple behavior change techniques (BCTs) to maximize effectiveness. Although, in theory, BCTs can amplify each other, the available meta-analyses have not been able to identify specific combinations of techniques that provide synergistic effects. This study overcomes some of the shortcomings in the current methodology by applying classification and regression trees (CART) to meta-analytic data in a special way, referred to as Meta-CART. The aim was to identify particular combinations of BCTs that explain intervention success. A reanalysis of data from Michie, Abraham, Whittington, McAteer, and Gupta (2009) was performed. These data included effect sizes from 122 interventions targeted at physical activity and healthy eating, and the coding of the interventions into 26 BCTs. A CART analysis was performed using the BCTs as predictors and treatment success (i.e., effect size) as outcome. A subgroup meta-analysis using a mixed effects model was performed to compare the treatment effect in the subgroups found by CART. Meta-CART identified the following most effective combinations: Provide information about behavior-health link with Prompt intention formation (mean effect size ḡ = 0.46), and Provide information about behavior-health link with Provide information on consequences and Use of follow-up prompts (ḡ = 0.44). Least effective interventions were those using Provide feedback on performance without using Provide instruction (ḡ = 0.05). Specific combinations of BCTs increase the likelihood of achieving change in health behavior, whereas other combinations decrease this likelihood. Meta-CART successfully identified these combinations and thus provides a viable methodology in the context of meta-analysis.

Mechanical bowel preparation and oral antibiotic prophylaxis in colorectal surgery: Analysis of evidence and narrative review.

PubMed

Badia, Josep M; Arroyo-García, Nares

2018-05-14

The role of oral antibiotic prophylaxis and mechanical bowel preparation in colorectal surgery remains controversial. The lack of efficacy of mechanical preparation to improve infection rates, its adverse effects, and multimodal rehabilitation programs have led to a decline in its use. This review aims to evaluate current evidence on antegrade colonic cleansing combined with oral antibiotics for the prevention of surgical site infections. In experimental studies, oral antibiotics decrease the bacterial inoculum, both in the bowel lumen and surgical field. Clinical studies have shown a reduction in infection rates when oral antibiotic prophylaxis is combined with mechanical preparation. Oral antibiotics alone seem to be effective in reducing infection in observational studies, but their effect is inferior to the combined preparation. In conclusion, the combination of oral antibiotics and mechanical preparation should be considered the gold standard for the prophylaxis of postoperative infections in colorectal surgery. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Curcumin potentiates the anti-arthritic effect of prednisolone in Freund's complete adjuvant-induced arthritic rats.

PubMed

Kuncha, Madhusudana; Naidu, Vegi Ganga Modi; Sahu, Bidya Dhar; Gadepalli, Shankar Ganesh; Sistla, Ramakrishna

2014-01-01

The present study was aimed at investigating the effect of curcumin in combination with prednisolone for the effective treatment of arthritis with reduced side effects when glucocorticoids therapy is indicated. Arthritis was induced in wistar rats by subplantar injection of Freund's complete adjuvant, and animals were observed for the symptoms of arthritis during the period of 21 days. Combined treatment of curcumin with various doses of prednisolone (1.25, 2.5 and 5 mg/kg) was evaluated in order to ascertain the efficacy and toxicity induced by steroid. Arthritic animals showed significant increase in tumour necrosis factor-α and IL-1β levels in paw tissue and IL-1β in serum. Combined therapy of curcumin with low doses of prednisolone showed pronounced beneficial effect on joint swelling, leucocyte count and biochemical parameters compared with prednisolone groups. Among the different doses used in the study, prednisolone at 1.25 mg/kg in combination with curcumin showed beneficial anti-arthritic activity and also reduced the steroid toxicity. This is evidenced by increase in body weight, low toxicity to immune organs, reduction in leucocyte count, increase in spleen anti-oxidant enzymes and potent inhibition of cytokines in combination group. Therefore, combined treatment of curcumin with low doses of prednisolone may find therapeutic use in arthritis. © 2013 Royal Pharmaceutical Society.

Individual and combined effects of Aflatoxin B1, Deoxynivalenol and Zearalenone on HepG2 and RAW 264.7 cell lines.

PubMed

Zhou, Hongyuan; George, Saji; Hay, Crystal; Lee, Joel; Qian, He; Sun, Xiulan

2017-05-01

To understand the combinatorial toxicity of mycotoxins, we measured the effects of individual, binary and tertiary combinations of Aflatoxin B 1 (AFB 1 ), Deoxynivalenol (DON) and Zearalenone (ZEN) on the cell viability and cellular perturbations of HepG2 and RAW 264.7 cells. The nature of mycotoxins interactions was assessed using mathematical modeling (Chou-Talalay). Mechanisms of cytotoxicity were studied using high content screening (HCS) that probed cytotoxicity responses, such as changes in intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), intracellular calcium ([Ca 2+ ] i ) flux, and cell membrane damage. Our results showed that individual cytotoxicity of mycotoxins in a decreasing order was DON>AFB 1 >ZEN. Varying combinations of mycotoxins at differing concentrations showed different types of interactions. Most of the mixtures showed increasing toxic effects-synergism and/or addition while antagonistic effects were observed with combination of AFB 1 +ZEN. Generally, combination of mycotoxins showed significantly increased intracellular ROS production and [Ca 2+ ] i flux, and decreased MMP in both cell lines, showing that the synergistic and additive effects of mycotoxin combination originate from perturbations of multiple cellular functions. Additionally, this study demonstrated the applicability of HCS for gaining mechanistic understanding on the toxicity of individual as well as combinatorial mycotoxins, and also provided scientific bases for formulating regulatory policies. Copyright © 2017. Published by Elsevier Ltd.

Combined effect of pulsed electromagnetic field and sound wave on In vitro and In vivo neural differentiation of human mesenchymal stem cells.

PubMed

Choi, Yun-Kyong; Urnukhsaikhan, Enerelt; Yoon, Hee-Hoon; Seo, Young-Kwon; Cho, Hyunjin; Jeong, Jong-Seob; Kim, Soo-Chan; Park, Jung-Keug

2017-01-01

Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017. © 2016 American Institute of Chemical Engineers.

Florfenicol As a Modulator Enhancing Antimicrobial Activity: Example Using Combination with Thiamphenicol against Pasteurella multocida

PubMed Central

Wei, Chia-Fong; Shien, Jui-Hung; Chang, Shao-Kuang; Chou, Chi-Chung

2016-01-01

Synergistic effects between the same class of antibiotics are rarely reported. Our previous study found synergistic-like interaction between florfenicol (FFC) and thiamphenicol (TAP) against Staphylococcus aureus. Here, the enhanced antimicrobial activity was evaluated in 97 clinical isolates of both Gram-negative and Gram-positive bacteria. Susceptible strains were initially identified by checkerboard microdilution assay (fractional inhibitory concentration index [FICI] ≤ 0.625), followed by confirmation of synergism using the time-kill methodology (≥2 log10 CFU/ml reduction). In all, 43% of Pasteurella multocida tested were susceptible to the enhanced bactericidal effect. In chicken fowl cholera models, FFC and TAP combination at much lower dosage that is correspondent to their MIC deduction provided maximum protection in vivo. Furthermore, synergistic combination of FFC with oxytetracycline (OTC) against Pseudomonas aeruginosa in vitro was also demonstrated. Based on the enhanced uptake of TAP and OTC, FFC presumably elicits enhanced antimicrobial activity in an orderly manner through alteration of bacterial membrane permeability or efflux systems and subsequent increase of intracellular concentration of the antibiotics used in combination. Results of ethidium bromide accumulation assay and RNA-seq showed little evidence for the involvement of efflux pumps in the synergy but further investigation is required. This study suggests the potentiality of a novel combination regimen involving FFC as an initiating modulator effective against both Gram-positive and Gram-negative bacteria depending on the antibiotics that are combined. The observed improvement of bacteriostatic effect to bactericidal, and the extended effectiveness against FFC-resistant bacterial strains warrant further studies. PMID:27065961

THE COMBINED EFFECT OF PRECESSION AND CONVECTION ON THE DYNAMO ACTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei, Xing, E-mail: xing.wei@sjtu.edu.cn; Princeton University Observatory, Princeton, NJ 08544

2016-08-20

To understand the generation of the Earth’s magnetic field and those of other planets, we numerically investigate the combined effect of precession and convection on dynamo action in a spherical shell. Convection alone, precession alone, and the combined effect of convection and precession are studied at the low Ekman number at which the precessing flow is already unstable. The key result is that although precession or convection alone are not strong enough to support the dynamo action, the combined effect of precession and convection can support the dynamo action because of the resonance of precessional and convective instabilities. This resultmore » may explain why the geodynamo has been maintained for such a long time compared to the Martian dynamo.« less

Anti-tumor effects on the combination of photodynamic therapy with arsenic compound in TC-1 cells implanted C57BL/6 mice

NASA Astrophysics Data System (ADS)

Lee, Kyu Wan; Wen, Lan Ying; Bae, Su Mi; Park, Choong Hak; Jeon, Woo Kyu; Lee, Doo Yun; Ahn, Woong Shick

2009-06-01

The effects of As4O6 were studied as adjuvant on photodynamic therapy. As4O6 is considered to have anticancer activity via several biological actions such as free radical producing and inhibition of VEGF expression. In vitro experiments, cell proliferation and morphology were determined by MTT assay. Also, quantitative PCR array was performed to study the synergetic mechanism. Additionally, this study was supported by the finding that combination of photodynamic therapy and As4O6 shows an inhibition effect of tumor growth in C57BL/6 mice with TC-1 cells xenographs in vivo. Radachlorin and As4O6 significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P < 0.05). Antiproliferative effect of combination treatment was significantly higher than those of TC-1 cells treated with either photodynamic therapy or As4O6 (62.4 and 52.5% decrease, respectively, compared to photodynamic therapy or As4O6 alone, P < 0.05). In addition, cell proliferation in combination of photodynamic therapy and As4O6 treatment significantly decreased by 77.4% compared to vehicle-only treated TC-1 cells (P < 0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21Cip1, Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As4O6. Besides, the immunology response NEAT pathway (Ly- 12, CD178 and IL-2) also modulated after combination treatment of photodynamic therapy and As4O6. This combination effect apparently shows a same pattern in vivo model. These findings suggest the benefit of the combination treatment of photodynamic therapy and As4O6 for the inhibition of cervical cancer growth.

Impact of co-administration of oxycodone and smoked cannabis on analgesia and abuse liability.

PubMed

Cooper, Ziva D; Bedi, Gillinder; Ramesh, Divya; Balter, Rebecca; Comer, Sandra D; Haney, Margaret

2018-02-05

Cannabinoids combined with opioids produce synergistic antinociceptive effects, decreasing the lowest effective antinociceptive opioid dose (i.e., opioid-sparing effects) in laboratory animals. Although pain patients report greater analgesia when cannabis is used with opioids, no placebo-controlled studies have assessed the direct effects of opioids combined with cannabis in humans or the impact of the combination on abuse liability. This double-blind, placebo-controlled, within-subject study determined if cannabis enhances the analgesic effects of low dose oxycodone using a validated experimental model of pain and its effects on abuse liability. Healthy cannabis smokers (N = 18) were administered oxycodone (0, 2.5, and 5.0 mg, PO) with smoked cannabis (0.0, 5.6% Δ 9 tetrahydrocannabinol [THC]) and analgesia was assessed using the Cold-Pressor Test (CPT). Participants immersed their hand in cold water (4 °C); times to report pain (pain threshold) and withdraw the hand from the water (pain tolerance) were recorded. Abuse-related effects were measured and effects of oxycodone on cannabis self-administration were determined. Alone, 5.0 mg oxycodone increased pain threshold and tolerance (p ≤ 0.05). Although active cannabis and 2.5 mg oxycodone alone failed to elicit analgesia, combined they increased pain threshold and tolerance (p ≤ 0.05). Oxycodone did not increase subjective ratings associated with cannabis abuse, nor did it increase cannabis self-administration. However, the combination of 2.5 mg oxycodone and active cannabis produced small, yet significant, increases in oxycodone abuse liability (p ≤ 0.05). Cannabis enhances the analgesic effects of sub-threshold oxycodone, suggesting synergy, without increases in cannabis's abuse liability. These findings support future research into the therapeutic use of opioid-cannabinoid combinations for pain.

The Antinociceptive Effects of Tramadol and/or Gabapentin on Rat Neuropathic Pain Induced by a Chronic Constriction Injury.

PubMed

Corona-Ramos, Janette Nallely; De la O-Arciniega, Minarda; Déciga-Campos, Myrna; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

2016-08-01

Preclinical Research The current work evaluates the interaction between two commonly used drugs, tramadol (Tra) and gabapentin (Gbp). Dose-response curves (DRC) and isobolographic analysis were used to confirm their synergistic antihyperalgesic and anti-allodynic responses in a rat neuropathic pain model involving chronic constriction injury of the sciatic nerve and in von Frey and acetone tests. Tra and Gbp produced dose-dependent antihyperalgesic and anti-allodynic effects. Dose-response studies of combinations of Tra and Gbp in combination showed the DRC was leftward-shifted compared to the DRCs for each compound alone. One combination demonstrated both antihyperalgesic and anti-allodynic effects greater than those observed after individual administration. The remaining combinations demonstrated an additive effect. The Tra+Gbp combination demonstrated a potentiative effect with smaller doses of Tra. Additionally, it was determined lethal dose 50 (LD50 ) of Tra alone and tramadol + Gbp 10 using mice to 48 h post administration. The DRC (death) were similar for Tra alone and in Tra in combination, despite the improved effectiveness of Tra in the presence of GBP, 10 mg/kg. A combination of these drugs could be effective in neuropathic pain therapy because they can produce potentiative (at a low dose) or additive effects. Drug Dev Res 77 : 217-226, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells

PubMed Central

Zhou, Weiqiang; Feng, Xiuyan; Han Han; Guo, Shanchun; Wang, Guangdi

2016-01-01

Previous studies showed that either histone deacetylase (HDAC) inhibitors or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in tumor cells including breast cancer. However, the underling mechanisms of combining HDAC inhibitors with TRAIL in the treatment of breast cancer are poorly understood. In this study, we determined the ability of SAHA and TRAIL as single agents or in combination to inhibit the growth and survival of MCF-7 and MDA-MB-231 breast cancer cells. Our results demonstrate that the distinct effects of SAHA or TRAIL individually and in combination on the proliferation, cell viability, apoptosis, cell cycle distribution, and morphological changes of MDA-MB-231 and MCF-7 cells. We further determined the different effects of SAHA or TRAIL alone and combining SAHA with TRAIL on the expression of a number of apoptosis-related molecules, cell cycle, growth factors and their receptors in cancer cells. Our results demonstrated that the combinatorial treatment of SAHA and TRAIL may target multiple pathways and serve as an effective therapeutic strategy against breast cancer. An improved understanding of the molecular mechanisms may facilitate either SAHA or TRAIL targeted use and the selection of suitable combinations. PMID:27292433

Effects of combined lime and fly ash stabilization on the elastic moduli of montmorillonitic soils : final report.

DOT National Transportation Integrated Search

1988-04-01

A laboratory study using bentonite to simulate the montmorillonite component of soils common to Louisiana was undertaken to evaluate the effects of combined lime and fly ash additions on stabilization reactions. Samples containing bentonite (75 weigh...

Effectiveness of Manual Therapy Combined With Physical Therapy in Treatment of Patellofemoral Pain Syndrome: Systematic Review.

PubMed

Espí-López, Gemma Victoria; Arnal-Gómez, Anna; Balasch-Bernat, Mercè; Inglés, Marta

2017-06-01

The purpose of this study was to conduct a review of randomized controlled trials (RCTs) to determine the treatment effectiveness of the combination of manual therapy (MT) with other physical therapy techniques. Systematic searches of scientific literature were undertaken on PubMed and the Cochrane Library (2004-2014). The following terms were used: "patellofemoral pain syndrome," "physical therapy," "manual therapy," and "manipulation." RCTs that studied adults diagnosed with patellofemoral pain syndrome (PFPS) treated by MT and physical therapy approaches were included. The quality of the studies was assessed by the Jadad Scale. Five RCTs with an acceptable methodological quality (Jadad ≥ 3) were selected. The studies indicated that MT combined with physical therapy has some effect on reducing pain and improving function in PFPS, especially when applied on the full kinetic chain and when strengthening hip and knee muscles. The different combinations of MT and physical therapy programs analyzed in this review suggest that giving more emphasis to proximal stabilization and full kinetic chain treatments in PFPS will help better alleviation of symptoms.

Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index.

PubMed

Nieuwenhuijs, Diederik J F; Olofsen, Erik; Romberg, Raymonda R; Sarton, Elise; Ward, Denham; Engbers, Frank; Vuyk, Jaap; Mooren, Rene; Teppema, Luc J; Dahan, Albert

2003-02-01

Since propofol and remifentanil are frequently combined for monitored anesthesia care, we examined the influence of the separate and combined administration of these agents on cardiorespiratory control and bispectral index in humans. The effect of steady-state concentrations of remifentanil and propofol was assessed in 22 healthy male volunteer subjects. For each subject, measurements were obtained from experiments using remifentanil alone, propofol alone, and remifentanil plus propofol (measured arterial blood concentration range: propofol studies, 0-2.6 microg/ml; remifentanil studies, 0-2.0 ng/ml). Respiratory experiments consisted of ventilatory responses to three to eight increases in end-tidal Pco2 (Petco2). Invasive blood pressure, heart rate, and bispectral index were monitored concurrently. The nature of interaction was assessed by response surface modeling using a population approach with NONMEM. Values are population estimate plus or minus standard error. A total of 94 responses were obtained at various drug combinations. When given separately, remifentanil and propofol depressed cardiorespiratory variables in a dose-dependent fashion (resting V(i) : 12.6 +/- 3.3% and 27.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; V(i) at fixed Petco of 55 mmHg: 44.3 +/- 3.9% and 57.7 +/- 3.5% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively; blood pressure: 9.9 +/- 1.8% and 3.7 +/- 1.1% depression at 1 microg/ml propofol and 1 ng/ml remifentanil, respectively). When given in combination, their effect on respiration was synergistic (greatest synergy observed for resting V(i)). The effects of both drugs on heart rate and blood pressure were modest, with additive interactions when combined. Over the dose range studied, remifentanil had no effect on bispectral index even when combined with propofol (inert interaction). These data show dose-dependent effects on respiration at relatively low concentrations of propofol and remifentanil. When combined, their effect on respiration is strikingly synergistic, resulting in severe respiratory depression.

Effects of Combining a Brief Cognitive Intervention with Transcranial Direct Current Stimulation on Pain Tolerance: A Randomized Controlled Pilot Study.

PubMed

Powers, Abigail; Madan, Alok; Hilbert, Megan; Reeves, Scott T; George, Mark; Nash, Michael R; Borckardt, Jeffrey J

2018-04-01

Cognitive behavioral therapy has been shown to be effective for treating chronic pain, and a growing literature shows the potential analgesic effects of minimally invasive brain stimulation. However, few studies have systematically investigated the potential benefits associated with combining approaches. The goal of this pilot laboratory study was to investigate the combination of a brief cognitive restructuring intervention and transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex in affecting pain tolerance. Randomized, double-blind, placebo-controlled laboratory pilot. Medical University of South Carolina. A total of 79 healthy adult volunteers. Subjects were randomized into one of six groups: 1) anodal tDCS plus a brief cognitive intervention (BCI); 2) anodal tDCS plus pain education; 3) cathodal tDCS plus BCI; 4) cathodal tDCS plus pain education; 5) sham tDCS plus BCI; and 6) sham tDCS plus pain education. Participants underwent thermal pain tolerance testing pre- and postintervention using the Method of Limits. A significant main effect for time (pre-post intervention) was found, as well as for baseline thermal pain tolerance (covariate) in the model. A significant time × group interaction effect was found on thermal pain tolerance. Each of the five groups that received at least one active intervention outperformed the group receiving sham tDCS and pain education only (i.e., control group), with the exception of the anodal tDCS + education-only group. Cathodal tDCS combined with the BCI produced the largest analgesic effect. Combining cathodal tDCS with BCI yielded the largest analgesic effect of all the conditions tested. Future research might find stronger interactive effects of combined tDCS and a cognitive intervention with larger doses of each intervention. Because this controlled laboratory pilot employed an acute pain analogue and the cognitive intervention did not authentically represent cognitive behavioral therapy per se, the implications of the findings on chronic pain management remain unclear.

Beneficial effects of the combination of amlodipine and losartan for lowering blood pressure in spontaneously hypertensive rats.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Kang, Kyung Koo; Kim, Jeong Hoon; Ahn, Byoung Ok; Yoo, Moohi

2009-03-01

A combination of antihypertensive agents can better control blood pressure and reduce the number and severity of side effects than a monotherapy. Since both CCBs (calcium channel blockers) and ARBs (angiotensin II receptor type-1 blockers) are current and effective antihypertensive drugs, this study assessed the synergistic antihypertensive effects as well as the optimal combination ratio of these two drugs. Amlodipine (3 mg/kg) or losartan (30 mg/kg) alone or a combination of each drug at a ratio 1:10 and 1:20 was administered orally to spontaneously hypertensive rats (SHR). A four-week treatment of either 3 mg/kg amlodipine or 30 mg/kg losartan alone decreased the systolic blood pressure (SBP). However, their combination significantly lowered the SBP from the 3(rd) week, and there was a positive correlation between this reduction in blood pressure and the improvement in arterial endothelium-dependent relaxation. In addition, the combination therapy (1:20) decreased both the cardiac mass and left ventricular weight to a greater extent than with either amlodipine or losartan alone. The collagen content in the cardiac tissue was also significantly lower after the 4-week combination therapy (1:10). These results suggest that the combined use of amlodipine and losartan might be more effective in treating hypertension than a monotherapy.

Efficient killing effect of osteosarcoma cells by cinobufacini and cisplatin in combination.

PubMed

Huang, Tao; Gong, Wei-Hua; Li, Xiu-Cheng; Zou, Chun-Ping; Jiang, Guang-Jian; Li, Xu-Hui; Qian, Hao

2012-01-01

To study the killing effects on osteosarcoma cells of cinobufacini and cisplatin in combination and the related mechanisms so as to explore the chemotherapeutic method with integrated traditional Chinese and Western medicines. Cinobufacini and cisplatin were applied to OS732 cells singly or jointly and survival rates were measured by MTT assay. Changes in cellular shape were observed with inverted phase contrast and fluorescence microscopy and apoptosis rates were analyzed with flow cytometry (FCM). Immunocytochemistry were used to examine the Fas expression of OS732 cells. The combination of cinobufacini and cisplatin had the effect of up-regulating Fas expression and inducing apoptosis. The survival rate of combined application of 100 μg/ml cinobufacini and 1 μg/ml cisplatin on OS-732 cells was significantly lower than with either of the agents alone (p<0.01). Changes in cellular shape and apoptotic rates also indicated the apoptosis-inducing effects of combined application were much enhanced. The combination of cinobufacini and cisplatin demonstrated strong killing effects on OS-732 cells which might be related to up-regulation of Fas expression.

Synergistic anti-inflammatory effects of Nobiletin and Sulforaphane in lipopolysaccharide-stimulated RAW 264.7 cells

PubMed Central

Guo, Shanshan; Qiu, Peiju; Xu, Guang; Wu, Xian; Dong, Ping; Yang, Guanpin; Zheng, Jinkai; McClements, David Julian; Xiao, Hang

2012-01-01

Inflammation plays important roles in initiation and progress of many diseases including cancers in multiple organ sites. Herein, we investigated the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN) in combination. Non-cytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The results showed that combined NBN and SFN treatments produced much stronger inhibitory effects on the production of nitric oxide (NO) than NBN or SFN alone at higher concentrations. These enhanced inhibitory effects were synergistic based on the isobologram analysis. Western blot analysis showed that combined NBN and SFN treatments synergistically decreased iNOS and COX-2 protein expression levels and induced heme oxygenase-1 (HO-1) protein expression. Real-time PCR analysis indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels, and synergistically increased HO-1 mRNA levels. Overall our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells. PMID:22335189

Drink refusal training as part of a combined behavioral intervention: Effectiveness and mechanisms of change

PubMed Central

Witkiewitz, Katie; Donovan, Dennis M.; Hartzler, Bryan

2012-01-01

Objective Many trials have demonstrated the effectiveness of cognitive behavioral interventions for alcohol dependence, yet few studies have examined why particular treatments are effective. This study was designed to evaluate whether drink refusal training was an effective component of a combined behavioral intervention (CBI) and whether change in self-efficacy was a mechanism of change following drink refusal training for individuals with alcohol dependence. Method The current study is a secondary analysis of data from the COMBINE study, a randomized clinical trial that combined pharmacotherapy with behavioral intervention in the treatment of alcohol dependence. The goal of the current study was to examine whether a drink refusal skills training module, administered as part of a 16-week CBI (n=776; 31% female, 23% non-White, average age=44) predicted changes in drinking frequency and self-efficacy during and following the CBI, and whether changes in self-efficacy following drink refusal training predicted changes in drinking frequency up to one year following treatment. Results Participants (n=302) who received drink refusal skills training had significantly fewer drinking days during treatment (d=0.50) and up to one year following treatment (d=0.23). In addition the effect of the drink refusal skills training module on drinking outcomes following treatment was significantly mediated by changes in self-efficacy, even after controlling for changes in drinking outcomes during treatment (proportion mediated = 0.47). Conclusions Drink refusal training is an effective component of CBI and some of the effectiveness may be attributed to changes in client self-efficacy. PMID:22289131

Effectiveness of monotherapy and combined therapy with calcitonin and minodronic acid hydrate, a bisphosphonate, for early treatment in patients with new vertebral fractures: An open-label, randomized, parallel-group study.

PubMed

Tanaka, Shinya; Yoshida, Akira; Kono, Shinjiro; Ito, Manabu

2017-05-01

Evidence related to the effectiveness of combination drug therapy for the treatment of osteoporosis is currently considered insufficient. Therefore, this study was performed to clarify the effects of monotherapy, and combination therapy, with a bisphosphonate (minodronic acid hydrate), a bone resorption inhibitor, and calcitonin (elcatonin), which is effective for the alleviation of pain due to vertebral fractures in osteoporotic patients. Study participants comprised of 51 female subjects with post-menopausal osteoporosis, whose main complaint was acute lower back pain caused by vertebral fractures. Subjects were randomly allocated into three groups and then administered with either intramuscular injections of elcatonin at a dose of 20 units weekly, minodronic acid hydrate at a dose of 1 mg daily, or a combination of these two drugs. As primary endpoints, time-dependent changes in levels of pain were assessed using a visual analog scale from baseline to 6 months of duration. In addition, we examined the effects of monotherapies, and a combination therapy on bone resorption, with changes in bone mineral density at 4 sites and advanced hip assessment parameters from baseline to 6 months. A two-tailed significance level of 5% was used for hypothesis testing. Elcatonin monotherapy showed some alleviation of pain immediately after any vertebral fractures, which was more than in the minodronic acid hydrate monotherapy group. In addition, the minodronic acid hydrate monotherapy group experienced more effective inhibited bone resorption than the elcatonin monotherapy group. In the combination therapy, the efficacy for alleviating pain and inhibiting bone resorption was equivalent to the effect observed in the elcatonin and minodronic acid hydrate monotherapy groups respectively, with further improved values of bone mineral density observed in the femoral neck and lumbar vertebrae, and in parameters of advanced hip assessment compared with both monotherapy groups. Combination therapy with elcatonin and minodronic acid hydrate appears to be an effective treatment for osteoporosis patients with lower back pain, caused by fresh vertebral fractures. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of Luteolin and Quercetin in Combination with Some Conventional Antibiotics against Methicillin-Resistant Staphylococcus aureus

PubMed Central

Usman Amin, Muhammad; Khurram, Muhammad; Khan, Taj Ali; Faidah, Hani S.; Ullah Shah, Zia; Ur Rahman, Shafiq; Haseeb, Abdul; Ilyas, Muhammad; Ullah, Naseem; Umar Khayam, Sahibzada Muhammad; Iriti, Marcello

2016-01-01

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region. PMID:27879665

[Effect of psychotropic drugs on activity of anticonvulsants in maximal electroshock test].

PubMed

Alikina, N A; Tregubov, A L; Kotegov, V P

2010-08-01

The effect ofpsychotropic drugs on the pharmacological properties of anticonvulsants was studied on white mice under maximal electroshock (ME) test conditions. Changes in the anticonvulsant effect of phenobarbital, diphenin, carbamazepine, hexamidine were traced upon their joint administration with psychotropic drugs, including piracetam, aminalon, amitriptyline, imizine, levomepromazine, and lithium oxybutyrate. An important result of research is the fact, that in no one of combinations the basic pharmacological effect of anticonvulsants was decreased. Based on the results of experiments, the most rational combinations of anticonvulsants with psychotropic preparations were revealed as manifested in the ME test. As criterion of rational combination was the increase in the activity of anticonvulsants and reduction of their toxicity in combination or at least invariance of this parameter. Rational combinations include (i) phenobarbital with piracetam, amitriptyline, levomepromazine, and lithium oxybutyrate; (ii) carbamazepine with piracetam; and (iii) hexamidine with amitriptyline, levomepromazine and imizine.

Cost-effectiveness analysis of hypertension treatment: controlled release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension--the Nifedipine and Candesartan Combination (NICE-Combi) Study.

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/ day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost ("Dominance") were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is "dominant" to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

Combination chemotherapy with Regorafenib in metastatic colorectal cancer treatment: A single center, retrospective study

PubMed Central

Lin, Chun-Yu; Lin, Tseng-Hsi; Chen, Chou-Chen; Chen, Ming-Cheng

2018-01-01

Background Regorafenib has been demonstrated as effective in refractory metastatic colorectal cancer. Combination use with chemotherapy has not been reported. We examined the efficacy and safety of adding chemotherapy to Regorafenib for the treatment of metastatic colorectal cancer(mCRC) patients. Methods We recruited mCRC patients at our institute who received either regorafenib monotherapy or regorafenib in combination with other chemotherapies. All patients had received chemo and target therapies and presented with disease progression before regorafenib treatment. The primary end point was overall survival. Findings Between September1, 2015 and May 31, 2017, 100 mCRC patients at our institute received regorafenib treatment. 39 patients were excluded due to poor performance, lack of timely treatment, or inadequate clinical data. A total of 34 patients received regorafenib combined with other chemotherapies, and 27 patients received regorafenib alone. Median follow up time was 10.4 and 6.1 months, respectively. The primary end point of median OS was higher in the combination group than in the single use group (20.9m vs 10.3m, p = 0.015). The most frequent adverse events were hand-foot skin reactions(16[47.1%]vs 12[44.4%]), fatigue(6[17.6%] vs 7[25.9%]), gastrointestinal discomfort (7[20.6%] vs 6[22.2%]), neutropenia (4[11.8%] vs 1[3.7%]), diarrhea(4[11.8%] vs 1[3.7%]), and mucositis(5[14.7%] vs 1[3.7%]). Conclusion The present study showed the efficacy and side effects of regorafenib combination treatment. Superiority in median OS and median PFS was noted in the combination group. The sampling difference between the study and observation groups effects justifies the comparison. Further clinical evidence of combination therapy efficacy is pending future studies. PMID:29304109

Combined effect of plant sterols and dietary fiber for the treatment of hypercholesterolemia.

PubMed

Castellanos-Jankiewicz, Ashley; Del Bosque-Plata, Laura; Tejero, M Elizabeth

2014-06-01

Hypercholesterolemia is a major contributor for disease burden in both the developed and developing world and an important risk factor for cardiovascular diseases (CVD). Phytosterols (PhS) and dietary fiber (DF) act as low density lipoprotein cholesterol (LDL-C) lowering agents, offering an effective treatment against high blood cholesterol and CVD. The aim of this review was to consider clinical evidence that analyzed the combination of PhS and DF in a cereal carrier for lowering LDL-C. Electronic database searches were carried out to identify peer-reviewed journal articles, from which five intervention studies that combined both components in a cereal carrier were identified and included in the present review. LDL-C lowering effects varied widely among studies, due to large heterogeneity in study design, subject baseline characteristics, length of the interventions, PhS and DF dosage and type of DF used. In relation to a time of intake, three studies suggested a frequency or distribution of the product's consumption during the day, while two studies did not consider this factor. Overall, the selected studies found significant differences on LDL-C concentrations, although not all of them reached the expected outcomes. Future research should be conducted to explore the effect that different types of DF exert on LDL-C when combined with PhS, and to analyze the effect of the product's time of intake in order to suggest an optimal moment of the day for its consumption.

Data analysis using a combination of independent component analysis and empirical mode decomposition

NASA Astrophysics Data System (ADS)

Lin, Shih-Lin; Tung, Pi-Cheng; Huang, Norden E.

2009-06-01

A combination of independent component analysis and empirical mode decomposition (ICA-EMD) is proposed in this paper to analyze low signal-to-noise ratio data. The advantages of ICA-EMD combination are these: ICA needs few sensory clues to separate the original source from unwanted noise and EMD can effectively separate the data into its constituting parts. The case studies reported here involve original sources contaminated by white Gaussian noise. The simulation results show that the ICA-EMD combination is an effective data analysis tool.

Pharmacokinetic-Pharmacodynamic Modeling of the Anti-Tumor Effect of Sunitinib Combined with Dopamine in the Human Non-Small Cell Lung Cancer Xenograft.

PubMed

Hao, Fangran; Wang, Siyuan; Zhu, Xiao; Xue, Junsheng; Li, Jingyun; Wang, Lijie; Li, Jian; Lu, Wei; Zhou, Tianyan

2017-02-01

To investigate the anti-tumor effect of sunitinib in combination with dopamine in the treatment of nu/nu nude mice bearing non-small cell lung cancer (NSCLC) A549 cells and to develop the combination PK/PD model. Further, simulations were conducted to optimize the administration regimens. A PK/PD model was developed based on our preclinical experiment to explore the relationship between plasma concentration and drug effect quantitatively. Further, the model was evaluated and validated. By fixing the parameters obtained from the PK/PD model, simulations were built to predict the tumor suppression under various regimens. The synergistic effect was observed between sunitinib and dopamine in the study, which was confirmed by the effect constant (GAMA, estimated as 2.49). The enhanced potency of dopamine on sunitinib was exerted by on/off effect in the PK/PD model. The optimal dose regimen was selected as sunitinib (120 mg/kg, q3d) in combination with dopamine (2 mg/kg, q3d) based on the simulation study. The synergistic effect of sunitinib and dopamine was demonstrated by the preclinical experiment and confirmed by the developed PK/PD model. In addition, the regimens were optimized by means of modeling as well as simulation, which may be conducive to clinical study.

Activities of Antibiotic Combinations against Resistant Strains of Pseudomonas aeruginosa in a Model of Infected THP-1 Monocytes

PubMed Central

Buyck, Julien M.

2014-01-01

Antibiotic combinations are often used for treating Pseudomonas aeruginosa infections but their efficacy toward intracellular bacteria has not been investigated so far. We have studied combinations of representatives of the main antipseudomonal classes (ciprofloxacin, meropenem, tobramycin, and colistin) against intracellular P. aeruginosa in a model of THP-1 monocytes in comparison with bacteria growing in broth, using the reference strain PAO1 and two clinical isolates (resistant to ciprofloxacin and meropenem, respectively). Interaction between drugs was assessed by checkerboard titration (extracellular model only), by kill curves, and by using the fractional maximal effect (FME) method, which allows studying the effects of combinations when dose-effect relationships are not linear. For drugs used alone, simple sigmoidal functions could be fitted to all concentration-effect relationships (extracellular and intracellular bacteria), with static concentrations close to (ciprofloxacin, colistin, and meropenem) or slightly higher than (tobramycin) the MIC and with maximal efficacy reaching the limit of detection in broth but only a 1 to 1.5 (colistin, meropenem, and tobramycin) to 2 to 3 (ciprofloxacin) log10 CFU decrease intracellularly. Extracellularly, all combinations proved additive by checkerboard titration but synergistic using the FME method and more bactericidal in kill curve assays. Intracellularly, all combinations proved additive only based on both FME and kill curve assays. Thus, although combinations appeared to modestly improve antibiotic activity against intracellular P. aeruginosa, they do not allow eradication of these persistent forms of infections. Combinations including ciprofloxacin were the most active (even against the ciprofloxacin-resistant strain), which is probably related to the fact this drug was the most effective alone intracellularly. PMID:25348528

Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models.

PubMed

Watanabe, Takashi; Ohtani, Toshiyuki; Aihara, Masanori; Ishiuchi, Shogo

2013-04-01

Blockade of Ca(++)-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) inhibits the proliferation of human glioblastoma by inhibiting Akt phosphorylation, which is independent of the phosphatidylinositol 3-kinase pathway. Inhibiting platelet-derived growth factor receptor (PDGFR)-mediated phosphorylation causes growth inhibition in glioblastoma cells. The authors of this study investigated the effects of YM872 and AG1296, singly and in combination and targeting different pathways upstream of Akt, on Akt-mediated tumor growth in glioblastoma cells in vivo and in vitro. The expression of AMPAR, PDGFR, and c-kit in glioblastoma cells was analyzed via immunofluorescence. Glioblastoma cells, both in culture and in xenografts grown in mice, were treated with YM872 and AG1296, singly or in combination. Inhibition of tumor growth was observed after treatment in the xenograft model. Cell proliferation assays were performed using anti-Ki 67 antibody in vivo and in vitro. The CD34-positive tumor vessel counts within the vascular hot spots of tumor specimens were evaluated. Phosphorylation of Akt was studied using Western blot analysis. Combined administration of YM872 and AG1296 had a significant enhanced effect on the inhibition of cell proliferation and reduction of tumor vascularity in the xenograft model. These agents singly and in combination demonstrated a significant reduction of Akt phosphorylation at Ser473 and inhibition of tumor proliferation in vitro, although combined administration had no enhanced antitumor effects. The strongly enhanced antitumor effect of this combination therapy in vivo rather than in vitro may be attributable to disruption of the aberrant vascular niche. This combination therapy might provide substantial benefits to patients with glioblastoma.

Effect of combination of thalidomide and sulfasalazine in experimentally induced inflammatory bowel disease in rats.

PubMed

Prakash, O; Medhi, B; Saikia, U N; Pandhi, P

2011-09-01

Thalidomide provided significant protection against tri nitro benzene sulfonic acid induced colitis. Combination therapy also reduced colonic inflammation and all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and tumor necrosis factor-alpha, estimation) were significant as compared to control as well as thalidomide alone treated group. Combination therapy showed additive effect of thalidomide which restored lipid peroxidation as well as reduced myeloperoxidase and TNF-a towards the normal levels. Morphological and histological scores were significantly reduced in combination groups. In experimental model of colitis, oral administration of thalidomide (150 mg/kg) alone as well as its combination with sulfasalazine (360 mg/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of thalidomide with sulfasalazine in rat colitis model which requires further confirmation in human studies.

Combining the α1-Adrenergic Receptor Antagonist, Prazosin, with the β-Adrenergic Receptor Antagonist, Propranolol, Reduces Alcohol Drinking More Effectively Than Either Drug Alone

PubMed Central

Rasmussen, Dennis D; Beckwith, Lauren E; Kincaid, Carrie L; Froehlich, Janice C

2014-01-01

Background Evidence suggests that activation of the noradrenergic system may contribute to alcohol drinking in animals and humans. Our previous studies demonstrated that blocking α1-adrenergic receptors with the antagonist, prazosin, decreased alcohol drinking in rats under various conditions. Since noradrenergic activation is also regulated by β-adrenergic receptors, we now examine the effects of the β-adrenergic receptor antagonist, propranolol, alone or in combination with prazosin, on alcohol drinking in rats selectively bred for high voluntary alcohol intake and alcohol preference (P line). Methods Two studies were conducted with male P rats. In study one, rats were allowed to become alcohol-dependent during 14 weeks of ad libitum access to food, water and 20% alcohol and the effect of propranolol (5–15 mg/kg, IP) and prazosin (1–2 mg/kg, IP) on alcohol intake during withdrawal were assessed. In study two, the effect of propranolol (5 mg/kg, IP) and prazosin (2 mg/kg, IP) on alcohol intake following prolonged imposed abstinence was assessed. Results Alcohol drinking following propranolol treatment was variable, but the combination of propranolol + prazosin consistently suppressed alcohol drinking during both alcohol withdrawal and following prolonged imposed abstinence, and the combination of these two drugs was more effective than was treatment with either drug alone. Conclusions Treatment with prazosin + propranolol, or a combination of other centrally active α1- and β-adrenergic receptor antagonists, may assist in preventing alcohol relapse in some individuals. PMID:24891220

SPATHOLOBUS SUBERECTUS STEM EXTRACT IMPROVES THE PROTECTIVE EFFECT OF HEPARIN ON CERULEIN-INDUCED PANCREATITIS.

PubMed

Shao, Zhengyi

2017-01-01

The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. Pancreatitis was induced pancreatitis by cerulean (50μg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1β (IL-Ιβ) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-Ιβ and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.

The effects of energy drink in combination with alcohol on performance and subjective awareness.

PubMed

Alford, Chris; Hamilton-Morris, Jennifer; Verster, Joris C

2012-08-01

This study investigated the coadministration of an energy drink with alcohol to study the effects on subjective intoxication and objective performance. This study aims to evaluate the objective and subjective effects of alcohol versus placebo at two alcohol doses, alone and in combination with an energy drink, in a balanced order, placebo-controlled, double-blind design. Two groups of ten healthy volunteers, mean (SD) age of 24 (6.5), participated in the study. One group consumed energy drink containing 80 mg of caffeine and the other consumed a placebo drink, with both receiving two alcohol doses (0.046 and 0.087% breathalyser alcohol concentration). Tests included breath alcohol assessment, objective measures of performance (reaction time, word memory and Stroop task) and subjective visual analogue mood scales. Participants showed significantly impaired reaction time and memory after alcohol compared to the no alcohol condition and had poorer memory after the higher alcohol dose. Stroop performance was improved with the energy drink plus alcohol combination compared to the placebo drink plus alcohol combination. Participants felt significant subjective dose-related impairment after alcohol compared to no alcohol. Neither breath alcohol concentration nor the subjective measures showed a significant difference between the energy drink and the placebo energy drink when combined with alcohol. Subjective effects reflected awareness of alcohol intoxication and sensitivity to increasing alcohol dose. There were no overall significant group differences for subjective measures between energy drink and placebo groups in the presence of alcohol and no evidence that the energy drink masked the subjective effects of alcohol at either dose.

A multistressor, multitrait approach to assessing the effects of wind and dust on Eucalyptus tereticornis.

PubMed

Leonard, Ryan J; McArthur, Clare; Hochuli, Dieter F

2016-08-01

Plants are routinely subjected to multiple environmental stressors, and the ability to respond to these stressors determines species survival and ecological breadth. Despite stressors such as wind and dust significantly influencing plant development, morphology, and chemistry, the combined influence of these factors is yet to be investigated. We used a manipulative glasshouse approach to compare the morphological, physiological, and biomechanical responses of Eucalyptus tereticornis to the independent and combined effects of wind and dust. Wind decreased both E. tereticornis height and stem flexural stiffness. Additionally, wind had no effect on leaf physiology, nor did dust have any significant effect on any of the traits measured. Our results suggest that wind and dust in combination may have an additive effect on several plant traits and provide new insight into the effects and importance of studying wind, dust, and different stress combinations. © 2016 Botanical Society of America.

Combination of imatinib and clotrimazole enhances cell growth inhibition in T47D breast cancer cells.

PubMed

Motawi, Tarek M K; Sadik, Nermin A H; Fahim, Sally A; Shouman, Samia A

2015-05-25

Imatinib mesylate (IM), a tyrosine kinase inhibitor, is used as targeted cancer therapy. However, mono-targeting by IM does not always achieve full tumor eradication and thus it is recommended to combine IM with other anticancer agents. Clotrimazole (CLT) is an antifungal azole derivative with promising anticancer effects due to inhibiting the activity of glycolytic enzymes. The present study aimed to evaluate the effect of combining CLT with IM on breast cancer cell line in an attempt to establish effective new combination. T47D human breast cancer cell line was treated with different concentrations of IM and/or CLT for 48 h. IM-CLT interaction was determined by isobologram equation and combination index. Cell viability was confirmed by measuring LDH activity. As indicators of glycolysis inhibition, the expression of hexokinase-2 (HK-2) and 6-phosphofructo-1-kinase (PFK-1) plus the activity of intracellular lactate dehydrogenase (LDH) and pyruvate kinase (PK) were determined. In addition, glucose consumption and adenosine triphosphate (ATP) production were measured. Moreover, nitric oxide (NO), vascular endothelial growth factor (VEGF) and hypoxia inducible factor-α (HIF-α) were also determined as they are modulators for glycolysis. This study demonstrated that IM or CLT synergistically inhibited cell growth in T47D as shown by combination and dose reduction indices. The combination of 15 μM IM and 20 μM CLT significantly decreased glucose consumption, activity of both PK and intracellular LDH, while increased leaked LDH, VEGF and NO in the medium compared to each drug alone. Furthermore the combination decreased gene expression of HK-2, PFK-1 and ATP content compared to the control. In conclusion, the synergistic effect of CLT on IM cytotoxicity in T47D cell line maybe mediated through inhibition of glycolysis and increasing both NO and VEGF. Further studies are required to confirm the efficiency and safety of this combination. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Combined effect of synthetic enterocin CRL35 with cell wall, membrane-acting antibiotics and muranolytic enzymes against Listeria cells.

PubMed

Salvucci, E; Hebert, E M; Sesma, F; Saavedra, L

2010-08-01

To evaluate the inhibition effectiveness of enterocin CRL35 in combination with cell wall, membrane-acting antibiotics and muranolytic enzymes against the foodborne pathogen Listeria. Synthetic enterocin CRL35 alone and in combination with monensin, bacitracin, gramicidin, mutanolysin and lysozyme were used in this study. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) index assays were performed using Listeria innocua 7 and Listeria monocytogenes FBUNT as sensitive strains. Antibiotics showed positive interactions with the bacteriocin in both strains tested. On the other hand, when mutanolysin and enterocin CRL35 were added to resting cells in a buffer system, the lytic effect of mutanolysin was enhanced. However, the addition of mutanolysin showed no effect on the growth of L. innocua 7 cells in a culture medium. Moreover, mutanolysin allowed the overgrowth of L. innocua 7 cells to an OD similar to control cells in the presence of inhibitory concentration of enterocin CRL35. In contrast, the combination of lysozyme and enterocin CRL35 resulted in a 50% inhibition of the L. innocua 7 growth. Based on our results, we conclude that the combination of synthetic enterocin CRL35 with some antibiotics is effective against L. innocua 7 and L. monocytogenes FBUNT cells, and more importantly the amount of these agents to be used was considerably reduced. The effectiveness of the combination of synthetic enterocin CRL35 with muramidases seems to depend on complex environments, and more detailed studies need to be performed to elucidate this issue. Enterocin CRL35 represents a promising agent that not only can ensure the quality and safety of food but it can also be combined with several antimicrobial agents important in the medical field.

Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared with Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States.

PubMed

Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

2017-06-01

The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients. A 3-state Markov model (PD-L1 positive stable disease, PD-L1 negative stable disease, and progression and/or death) was developed using a U.S. societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free (PF) survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 U.S. dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. Nivolumab-ipilimumab combination therapy was not the cost-effective choice ($454,092 per PF quality-adjusted life-year [QALY]) compared with nivolumab monotherapy in a base case analysis at a willingness-to-pay threshold of $100,000 per PFQALY. Combination therapy and nivolumab monotherapy were cost-effective choices compared with ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment, but combination therapy had an improved incremental cost-effectiveness ratio (ICER) of $295,903 per PFQALY. Combination therapy became dominated by nivolumab, when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to < $21,555 per dose for combination therapy to have an ICER < $100,000 per PFQALY and to < $19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. Nivolumab-ipilimumab combination therapy was not cost-effective compared with nivolumab monotherapy, which was the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions, and future cost-effectiveness studies are completed. No funding supported this study. Merino was a contractor with EMD Serono at the time of this study but does not have any conflicts of interest and did not receive any funding related to this study. All other authors have no financial disclosures and no conflicts of interest. All the authors contributed to the study concept and design. Tran, McDowell, and Barcelon took the lead in data collection, along with Oh, Keyvani, and Merino. All authors except Merino contributed to data interpretation. The manuscript was written by Oh, Tran, McDowell, and Wilson and revised by Oh, Tran, McDowell, Wilson, and Keyvani. This analysis was presented at Academy of Managed Care Pharmacy Managed Care & Specialty Pharmacy Annual Meeting 2016, April 19-22, 2016, in San Francisco, California, and at the International Society for Pharmacoeconomics and Outcomes Research Annual International Meeting, May 21-25, 2016, in Washington DC.

Treatment of in vitro enterohemorrhagic Escherichia coli infection using phage and probiotics.

PubMed

Dini, C; Bolla, P A; de Urraza, P J

2016-07-01

To assay the combination of phage and probiotics against EHEC in vitro on infected Hep-2 cells. Phage and probiotics treatments on EHEC O157:H7-infected Hep-2 cells were assayed individually or combined. The effect of freeze-drying on phage and probiotic antimicrobial activity was also studied. While treatment with phage alone increased cell detachment caused by EHEC infection, the treatments with MM alone or in combination with phage proved to effectively diminish cell damage caused by EHEC infection. Combined treatment showed a decrease in apoptotic cell count of 57·3% and a reduction in EHEC adhesion to cell monolayer of 1·2 log CFU. The simultaneous use of phage and probiotics showed no antagonistic effect, and freeze-drying did not affect their antipathogenic activity. The combination of phage and probiotics has great potential for reducing the number of pathogens adhered to epithelial cells during EHEC O157:H7 infection and attenuating the cytotoxic effect derived from it. Further in vivo assays are needed for assessing the actual effectiveness of the treatment. This study presents a freeze-dried formulation of phage and probiotics capable of controlling EHEC infections and reducing epithelial cell damage in vitro. © 2016 The Society for Applied Microbiology.

The Effect of Acceleration Sprint and Zig-zag Drill Combination to Increase Students’ Speed and Agility

NASA Astrophysics Data System (ADS)

Bana, O.; Mintarto, E.; Kusnanik, N. W.

2018-01-01

The purpose of this research is to analyze the following factors: (1) how far the effect of exercise acceleration sprint on the speed and agility (2) how much influence the zig-zag drill combination to the speed and agility (3) and is there any difference between the effects of exercise acceleration sprint and practice zig-zag drill combination of the speed and agility. This research is quantitative with quasi-experimental approach. The design of this study is matching only design.This study was conducted on 33 male students who take part in extracurricular and divided into 3 groups with 11 students in each group. Group 1 was given training of acceleration sprint, group 2 was given zig-zag training combination drills of conventional and exercises for group 3, for 8 weeks. The data collection was using sprint 30 meter to test the speed and agility t-test to test agility. Data were analyzed using t-test and analysis of variance. The conclusion of the research is (1) there is a significant effect of exercise acceleration sprint for the speed and agility, (2) there is a significant influence combination zig-zag drills, on speed and agility (3) and exercise acceleration sprint have more effect on the speed and agility.

Effects on agitation with rivastigmine patch monotherapy and combination therapy with memantine in mild to moderate Alzheimer's disease: a multicenter 24-week prospective randomized open-label study (the Korean EXelon Patch and combination with mEmantine Comparative Trial study).

PubMed

Yoon, Soo J; Choi, Seong H; Na, Hae R; Park, Kyung-Won; Kim, Eun-Joo; Han, Hyun J; Lee, Jae-Hong; Shim, Young S; Na, Duk L

2017-03-01

Memantine is known to be effective in the treatment of the behavioral symptoms of dementia, especially agitation in moderate to severe Alzheimer's disease (AD). However, memantine and rivastigmine patch combination therapy has not been well studied in determining treatment effectiveness with mild to moderate AD patients. This was a multicenter, 24-week, prospective, randomized, open-label study design. A total 147 AD patients with Mini-Mental State Examination scores from 10 to 20 were randomly assigned to rivastigmine patch monotherapy and combination therapy with memantine groups. Agitation symptoms, using the Korean Version of the Cohen Mansfield Agitation Inventory were evaluated at baseline and at study end. Suppression and emergence of agitation symptoms were also evaluated. We carried out factor analyses to evaluate the interrelationship of agitation symptoms and to investigate treatment response in these symptoms. Factor analyses showed two symptom clusters: factor A - aggressive agitated behaviors - versus factor B - non-aggressive agitated behaviors. The rivastigmine patch monotherapy group showed significantly decreased factor B scores and had a tendency of decreased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor A scores. Conversely, the combination therapy group showed significantly increased Korean Version of the Cohen Mansfield Agitation Inventory total scores and factor B scores. Neither monotherapy nor combination therapy reduced the emergence of new agitation symptoms. In this trial of mild to moderate AD patients, the rivastigmine patch monotherapy group experienced a reduction of non-aggressive agitated behaviors. However, combination therapy with memantine did not show any benefit on the agitation associated with mild to moderate AD. Geriatr Gerontol Int 2017; 17: 494-499. © 2016 Japan Geriatrics Society.

Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study.

PubMed

Mutimer, D; Naoumov, N; Honkoop, P; Marinos, G; Ahmed, M; de Man, R; McPhillips, P; Johnson, M; Williams, R; Elias, E; Schalm, S

1998-06-01

Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination. All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction. The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance). Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Combining Solvent Isotope Effects with Substrate Isotope Effects in Mechanistic Studies of Alcohol and Amine Oxidation by Enzymes*

PubMed Central

Fitzpatrick, Paul F.

2014-01-01

Oxidation of alcohols and amines is catalyzed by multiple families of flavin-and pyridine nucleotide-dependent enzymes. Measurement of solvent isotope effects provides a unique mechanistic probe of the timing of the cleavage of the OH and NH bonds, necessary information for a complete description of the catalytic mechanism. The inherent ambiguities in interpretation of solvent isotope effects can be significantly decreased if isotope effects arising from isotopically labeled substrates are measured in combination with solvent isotope effects. The application of combined solvent and substrate (mainly deuterium) isotope effects to multiple enzymes is described here to illustrate the range of mechanistic insights that such an approach can provide. PMID:25448013

Effect of tea (Camellia sinensis) and olive (Olea europaea L.) leaves extracts on male mice exposed to diazinon.

PubMed

Al-Attar, Atef M; Abu Zeid, Isam M

2013-01-01

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors.

Effect of Tea (Camellia sinensis) and Olive (Olea europaea L.) Leaves Extracts on Male Mice Exposed to Diazinon

PubMed Central

Al-Attar, Atef M.; Abu Zeid, Isam M.

2013-01-01

The present study was aimed to evaluate the effects of tea and olive leaves extracts and their combination in male mice intoxicated with a sublethal concentration of diazinon. Exposure of mice to 6.5 mg/kg body weight of diazinon for seven weeks resulted in statistical increases of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase, creatine kinase, creatinine, glucose, triglycerides, and cholesterol, while the value of serum total protein was declined. Treating diazinon-intoxicated mice with tea and olive leaves extracts or their combination significantly attenuated the severe alterations in these hematobiochemical parameters. Moreover, the results indicated that the supplementation with combination of tea and olive leaves extracts led to more attenuation effect against diazinon toxicity. Additionally, these new findings suggest that the effect of tea and olive leaves extracts and their combination against toxicity of diazinon may be due to antioxidant properties of their chemical constituents. Finally, the present study indicated that the extracts of tea and olive leaves and their combination can be considered as promising therapeutic agents against hepatotoxicity, cardiotoxicity, nephrotoxicity, and metabolic disorders induced by diazinon and maybe by other toxicants and pathogenic factors. PMID:23691503

Combined use of clozapine and ECT: a review.

PubMed

Grover, Sandeep; Hazari, Nandita; Kate, Natasha

2015-06-01

This paper aims to review the available evidence for the use of clozapine and electroconvulsive therapy (ECT) in combination. Electronic searches were carried out to identify reports describing the combined use of clozapine and ECT. Forty reports including 208 patients were identified. The majority of reports were in the form of case reports and case series, with few retrospective and open-label studies. The majority of patients were aged between 18 and 65 years and diagnosed with schizophrenia or schizoaffective disorder. Most of the patients refractory to clozapine were started on ECT as an augmentation therapy; however, in some reports, both ECT and clozapine were started concurrently, and in few cases clozapine was started after ECT. In terms of effectiveness, 37.5-100% patients improved in short-term, and sustained long-term improvement (3 weeks to 24 months) was described in few studies. In terms of the side-effect profile, five patients each had delirium and tachycardia and only four patients were described to have prolonged seizures. Overall, the combination was considered effective and safe. There is evidence for the effectiveness and safety of the clozapine-ECT combination and it should be used in patients with treatment-resistant schizophrenia who do not respond to clozapine.

The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process

PubMed Central

Cristina Desoti, Vânia; Lazarin-Bidóia, Danielle; Martins Ribeiro, Fabianne; Cardoso Martins, Solange; da Silva Rodrigues, Jean Henrique; Ueda-Nakamura, Tania; Vataru Nakamura, Celso; Farias Ximenes, Valdecir; de Oliveira Silva, Sueli

2015-01-01

Chagas’ disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas’ disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death. PMID:26641473

The Combination of Vitamin K3 and Vitamin C Has Synergic Activity against Forms of Trypanosoma cruzi through a Redox Imbalance Process.

PubMed

Cristina Desoti, Vânia; Lazarin-Bidóia, Danielle; Martins Ribeiro, Fabianne; Cardoso Martins, Solange; da Silva Rodrigues, Jean Henrique; Ueda-Nakamura, Tania; Vataru Nakamura, Celso; Farias Ximenes, Valdecir; de Oliveira Silva, Sueli

2015-01-01

Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death.

The effects of L-theanine, caffeine and their combination on cognition and mood.

PubMed

Haskell, Crystal F; Kennedy, David O; Milne, Anthea L; Wesnes, Keith A; Scholey, Andrew B

2008-02-01

L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.

On their best behavior: how animal behavior can help determine the combined effects of species interactions and climate change.

PubMed

Harmon, Jason P; Barton, Brandon T

2013-09-01

The increasingly appreciated link between climate change and species interactions has the potential to help us understand and predict how organisms respond to a changing environment. As this connection grows, it becomes even more important to appreciate the mechanisms that create and control the combined effect of these factors. However, we believe one such important set of mechanisms comes from species' behavior and the subsequent trait-mediated interactions, as opposed to the more often studied density-mediated effects. Behavioral mechanisms are already well appreciated for mitigating the separate effects of the environment and species interactions. Thus, they could be at the forefront for understanding the combined effects. In this review, we (1) show some of the known behaviors that influence the individual and combined effects of climate change and species interactions; (2) conceptualize general ways behavior may mediate these combined effects; and (3) illustrate the potential importance of including behavior in our current tools for predicting climate change effects. In doing so, we hope to promote more research on behavior and other mechanistic factors that may increase our ability to accurately predict climate change effects. © 2013 New York Academy of Sciences.

Antimicrobial, antioxidant, and antitumor activity of epsilon-poly-L-lysine and citral, alone or in combination.

PubMed

Shi, Ce; Zhao, Xingchen; Liu, Zonghui; Meng, Rizeng; Chen, Xiangrong; Guo, Na

2016-01-01

Food safety is an important worldwide public health concern, and microbial contamination in foods not only leads to food deterioration and shelf life reduction but also results in economic losses and disease. The main aim of the present study was to evaluate the effect of epsilon-poly-L-lysine (ε-PL) and citral combination against Escherichia coli O157:H7 (E. coli O157:H7) strains. The preliminary antioxidant and antitumor activities were also studied. Synergism is a positive interaction created when two compounds combine and exert an inhibitory effect that is greater than the sum of their individual effects. The synergistic antimicrobial effect of ε-PL and citral was studied using the checkerboard method against E. coli O157:H7. The minimal inhibitory concentration, time-kill, and scanning electron microscope assays were used to determine the antimicrobial activity of ε-PL and citral alone or in combination; 2,2-diphenyl-1-picrylhydrazyl-scavenging assay and western blotting were used in antioxidant activity assays; cell viability assay was carried out to finish preliminary antitumor test. Minimal inhibitory concentrations of ε-PL and citral resisted to the five E. coli O157:H7 strains were 2-4 µg/mL and 0.5-1 µg/mL, and the fractional inhibitory concentration indices were 0.25-0.375. The results of time-kill assay revealed that a stronger bactericidal effect in a laboratory medium might be exerted in the combination against E. coli O157:H7 than that in a food model. The compounds alone or in combination exhibited a potential 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, and the expression of superoxide dismutase 1 and glutathione peroxidase 1 protein increased. The preliminary antitumor activity effect of the combination was better than ε-PL or citral alone. These findings indicated that the combination of ε-PL and citral could not only be used as a promising naturally sourced food preservative but also be used in the pharmaceutical industry.

Comparative study of clozapine, electroshock and the combination of ECT with clozapine in treatment-resistant schizophrenic patients.

PubMed

Masoudzadeh, A; Khalilian, A R

2007-12-01

The aim of this study was to compare the results of treatment with clozapine alone, Electroshock (ECT) alone and the combination of clozapine with ECT in treatment-resistant schizophrenic patients. Eighteen treatment-resistant schizophrenic patients were assigned to three equal groups: one group was given clozapine; one group was treated with ECT and one group was treated with the combination of clozapine and ECT. The treatment response was evaluated using the PANSS criteria and the data were analyzed with ANOVA. Combination therapy was superior to single modality therapy. The reduction of PANSS scores was 46% in the clozapine group, 40% in the ECT groups and 71% in the combination group, the difference between the combination group and the other groups was statistically significant (p < 0.05). Patients had a quick response to combination treatment, which resulted in a higher cure rate of positive and negative symptoms and improved the patients general performance. There were no significant adverse effects with combination treatment. Combination treatment with clozapine and ECT was safe and effective in treatment-resistant schizophrenic patients. It should be considered for the treatment of treatment-resistant schizophrenic patients.

Splenectomy combined with gastrectomy and immunotherapy for advanced gastric cancer.

PubMed

Miwa, H; Orita, K

1983-06-01

We studied the effects of a splenectomy in combination with immunotherapy on the survival of patients who had undergone a total gastrectomy. It was found that a splenectomy was not effective against advanced gastric cancer at stage III, and that the spleen should be retained for immunotherapy. Splenectomy for gastric cancer at terminal stage IV, particularly in combination with immunotherapy, produced not only augmentation of cellular immunity, but also increased survival.

A metabolomics strategy to assess the combined toxicity of polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs).

PubMed

Wang, Feidi; Zhang, Haijun; Geng, Ningbo; Ren, Xiaoqian; Zhang, Baoqin; Gong, Yufeng; Chen, Jiping

2018-03-01

The combined toxicity of mixed chemicals is usually evaluated according to several specific endpoints, and other potentially toxic effects are disregarded. In this study, we provided a metabolomics strategy to achieve a comprehensive understanding of toxicological interactions between mixed chemicals on metabolism. The metabolic changes were quantified by a pseudotargeted analysis, and the types of combined effects were quantitatively discriminated according to the calculation of metabolic effect level index (MELI). The metabolomics strategy was used to assess the combined effects of polycyclic aromatic hydrocarbons (PAHs) and short-chain chlorinated paraffins (SCCPs) on the metabolism of human hepatoma HepG2 cells. Our data suggested that exposure to a combination of PAHs and SCCPs at human internal exposure levels could result in an additive effect on the overall metabolism, whereas diverse joint effects were observed on various metabolic pathways. The combined exposure could induce a synergistic up-regulation of phospholipid metabolism, an additive up-regulation of fatty acid metabolism, an additive down-regulation of tricarboxylic acid cycle and glycolysis, and an antagonistic effect on purine metabolism. SCCPs in the mixture acted as the primary driver for the acceleration of phospholipid and fatty acid metabolism. Lipid metabolism disorder caused by exposure to a combination of PAHs and SCCPs should be an important concern for human health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of mixed cultures of biocontrol agents to control sheep nematodes.

PubMed

Baloyi, M A; Laing, M D; Yobo, K S

2012-03-23

Biological control is a promising non-chemical approach for the control of gastrointestinal nematodes of sheep. Use of combinations of biocontrol agents have been reported to be an effective method to increase the efficacy of biological control effects. In this study, combinations of either two Bacillus thuringiensis (Bt) or Clonostachys rosea (C. rosea) isolates and Bt+C. rosea isolates were evaluated in vitro in microtitre plates for their biocontrol activity on sheep nematodes. The Baermann technique was used to extract the surviving L3 larval stages of intestinal nematodes and counted under a dissecting microscope to determine the larval counts. Results indicate that there was a significant reduction of nematode counts due to combination of biocontrol agents (P<0.001). Combinations of Bt isolates reduced nematodes counts by 72.8%, 64% and 29.8%. The results revealed a control level of 57% when C. rosea isolates P3+P8 were combined. Combination of Bt and C. rosea isolates B10+P8 caused the greatest mortality of 76.7%. Most combinations were antagonistic, with only a few combinations showing an additive effect. None were synergistic. The isolate combinations were more effective than when isolates were used alone. Copyright © 2011 Elsevier B.V. All rights reserved.

Grape Polyphenol Signaling to Regulate Breast Cancer Metastasis

DTIC Science & Technology

2009-09-01

than individual compounds at inhibition of breast cancer progression. For this, we tested the effects of resveratrol, quercetin , and catechin, which...combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin , or catechin at inhibition of cell functions...Therefore, we decided to study the effects of resveratrol, quercetin , and catechin individually or combined (RQC) at low dietary concentrations on

Effect of simulated insect damage on growth and survival of northern red oak (Quercus rubra L.) seedlings

Treesearch

Susan L. Wright; Richard W. Hall; John W. Peacock

1989-01-01

Effects of simulated insect damage—artificial defoliation and root damage in combination with two levels of watering—were studied to determine the potential effect on northern red oak seedlings (Quercus rubra L.). Treatments and treatment combinations caused significant differences in stem diameter, percentage of stem dieback, and mortality....

Postantifungal effect of the combination of caspofungin with voriconazole and amphotericin B against clinical Candida krusei isolates.

PubMed

Oz, Yasemin; Kiremitci, Abdurrahman; Dag, Ilknur; Metintas, Selma; Kiraz, Nuri

2013-01-01

We evaluated the postantifungal effects (PAFEs) of caspofungin (CAS), voriconazole (VOR), amphotericin B (AmB), and the combinations of CAS + VOR and CAS + AmB against 30 clinical Candida krusei isolates at 0.25, 1 and 4 times the MIC of each individually and in the indicated combinations. Antifungals were removed after 1 hour and colony counts were performed at 0, 2, 6, 24, and 48 h. VOR did not display any measurable PAFE regardless of antifungal concentrations, while AmB and CAS exhibited dose-dependent PAFE. The most effective agent producing a prolonged PAFE in this study was CAS. Although the combination of CAS with VOR generated longer PAFEs at 0.25 and 1 times their respective MICs in comparison with CAS alone, this combination was indifferent rather than synergistic. However, the combination of CAS with AmB at 4 times their MICs exhibited the best performance, reducing the colony counts during the 48 h after removal of drugs and resulted in synergic interaction in respect to 20 (67%) isolates. Consequently, CAS has a prolonged PAFE in vitro against C. krusei isolates, and the combination of AmB + CAS may increase significantly the efficacy of CAS. Our data may be useful in optimizing dosing regimens for these agents and their combinations, although further studies are needed to explore the clinical usefulness of our results.

Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury

PubMed Central

Gao, Xiao-Ya; Huang, Jian-Ou; Hu, Ya-Fang; Gu, Yong; Zhu, Shu-Zhen; Huang, Kai-Bin; Chen, Jin-Yu; Pan, Su-Yue

2014-01-01

Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury. PMID:25404538

Effects of alcohol mixed with energy drink and alcohol alone on subjective intoxication.

PubMed

Ulbrich, Andrea; Hemberger, Sophie Helene; Loidl, Alexandra; Dufek, Stephanie; Pablik, Eleonore; Fodor, Sugarka; Herle, Marion; Aufricht, Christoph

2013-12-01

Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.

Combined effects of work-related stress in Her Majesty's Coastguard (HMCG).

PubMed

Kingdom, S E; Smith, A P

2012-01-01

Having initially reported on the overall level of stress in Her Majesty's Coastguard (HMCG), in a second study we found that a combined (negative) effects approach to stress was better able to identify the associated psychosocial risk factors than by using the well-documented Effort-Reward Imbalance (ERI) or Job Demand-Control Support (JDCS) models alone. Using the same combined effects method, this study now examines the negative health and wellbeing outcomes associated with the level of high stress found in this occupational group. Participants included 282 coastguards. A range of known stress outcomes were measured including: mental and physical health, accidents, risk taking, effects of memory, lifestyle, and job satisfaction. Significant associations were found with: anxiety, depression, number of sick days, perception that illness was caused or made worse by work, number of symptoms, medicines taken, insomnia, ability to maintain a desired body weight or take planned exercise and find time to relax and wind down, time spent on hobbies or interests, the impact of job on family life/family life on job, and job satisfaction. Sixteen negative outcomes were significantly associated with the combined effects approach, compared with 15 using ERI or 10 using JDCS alone. Results clearly demonstrated the harmful effects of stress in maritime related roles, other than those of seafarers and suggest that further research in this area would be useful. Further studies on the more flexible stress model, which allows for the examination of both established and new combinations of risk factors and associated outcomes, would also be beneficial.

Novel Combination of Prebiotics Galacto-Oligosaccharides and Inulin-Inhibited Aberrant Crypt Foci Formation and Biomarkers of Colon Cancer in Wistar Rats.

PubMed

Qamar, Tahir Rasool; Syed, Fatima; Nasir, Muhammad; Rehman, Habib; Zahid, Muhammad Nauman; Liu, Rui Hai; Iqbal, Sanaullah

2016-08-01

The selectivity and beneficial effects of prebiotics are mainly dependent on composition and glycosidic linkage among monosaccharide units. This is the first study to use prebiotic galacto-oligosaccharides (GOS) that contains β-1,6 and β-1,3 glycosidic linkages and the novel combination of GOS and inulin in cancer prevention. The objective of the present study is to explore the role of novel GOS and inulin against various biomarkers of colorectal cancer (CRC) and the incidence of aberrant crypt foci (ACF) in a 1,2-dimethyl hydrazine dihydrochloride (DMH)-induced rodent model. Prebiotic treatments of combined GOS and inulin (57 mg each), as well as individual doses (GOS: 76-151 mg; inulin 114 mg), were given to DMH-treated animals for 16 weeks. Our data reveal the significant preventive effect of the GOS and inulin combination against the development of CRC. It was observed that inhibition of ACF formation (55.8%) was significantly (p ≤ 0.05) higher using the GOS and inulin combination than GOS (41.4%) and inulin (51.2%) treatments alone. This combination also rendered better results on short-chain fatty acids (SCFA) and bacterial enzymatic activities. Dose-dependent effects of prebiotic treatments were also observed on cecum and fecal bacterial enzymes and on SCFA. Thus, this study demonstrated that novel combination of GOS and inulin exhibited stronger preventive activity than their individual treatments alone, and can be a promising strategy for CRC chemoprevention.

Central additive effect of Ginkgo biloba and Rhodiola rosea on psychomotor vigilance task and short-term working memory accuracy.

PubMed

Al-Kuraishy, Hayder M

2016-01-01

The present study investigates the effect of combined treatment with Ginkgo biloba and/or Rhodiola rosea on psychomotor vigilance task (PVT) and short-term working memory accuracy. A total number of 112 volunteers were enrolled to study the effect of G. biloba and R. rosea on PVT and short-term working memory accuracy as compared to placebo effects, the central cognitive effect was assessed by critical flicker-fusion frequency, PVT, and computerized N-back test. Placebo produced no significant effects on all neurocognitive tests measure P > 0.05 in normal healthy volunteers, G. biloba or R. rosea improve PVT and low to moderate working memory accuracy, The combined effect of R. rosea and G. biloba leading to more significant effect on PVT, all levels of short-term working memory accuracy and critical fusion versus flicker P < 0.01, more than of G. biloba or R. rosea when they used alone. The combined effect of R. rosea and G. biloba leading to a more significant effect on cognitive function than either G. biloba or R. rosea when they used alone.

The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome.

PubMed

Minozzi, Massimo; Costantino, Demetrio; Guaraldi, Claudia; Unfer, Vittorio

2011-11-01

Compare the effects of a combined contraceptive pill (OCP) in combination with myo-inositol (MI) on endocrine, metabolic, and clinical parameters in patients with polycystic ovary syndrome (PCOS). One hundred fifty-five patients with PCOS were enrolled in this prospective, open-label clinical study. Patients were assigned to receive oral treatment with OCP alone (estradiol (EE) 30 μg/gestodene 75 μg) or in combination with myo-inositol 4 g/die, for 12 months. OCP plus MI therapy resulted in a higher reduction of FG score compared with OCP alone therapy. The combined therapy (OCP plus MI) significantly decreased hyperinsulinaemia, by positively affecting the fasting insulin and glucose levels and homeostasis model assessment-insulin resistance parameters, while no significant changes were observed in the OCP group. Androgens serum levels decreased in both groups, but significantly more in the combined therapy group. The lipid profile was improved in the combined therapy group, by reducing low-density lipoprotein cholesterol levels and enhancing high-density lipoprotein cholesterol levels. Our data show that a combination of combined contraceptive pill and MI may be more effective in controlling endocrine, metabolic, and clinical profile in patients with PCOS than OCP alone, and may reduce insulin levels and insulin resistance. Hence, combined treatment may become a more effective long-term therapeutic choice for controlling PCOS symptoms.

Factors that lead to the use of crack cocaine in combination with marijuana in Brazil: a qualitative study.

PubMed

Gonçalves, Janaina R; Nappo, Solange A

2015-07-25

In Brazil, crack cocaine use remains a healthcare challenge due to the rapid onset of its pleasurable effects, its ability to induce craving and addiction, and the fact that it is easily accessible. Delayed action on the part of the Brazilian Government in addressing the drug problem has led users to develop their own strategies for surviving the effects of crack cocaine use, particularly the drug craving and psychosis. In this context, users have sought the benefits of combining crack cocaine with marijuana. Our aim was to identify the reasons why users combine crack cocaine with marijuana and the health implications of doing so. The present study is a qualitative study, using in-depth interviews and criteria-based sampling, following 27 crack cocaine users who combined its use with marijuana. Participants were recruited using the snowball sampling technique, and the point of theoretical saturation was used to define the sample size. Data were analyzed using the content analysis technique. The interviewees reported that the combination of crack cocaine use with marijuana provided "protection" (reduced undesirable effects, improved sleep and appetite, reduced craving for crack cocaine, and allowed the patients to recover some quality of life). Combined use of cannabis as a strategy to reduce the effects of crack exhibited several significant advantages, particularly an improved quality of life, which "protected" users from the violence typical of the crack culture. Crack use is considered a serious public health problem in Brazil, and there are few solution strategies. Within that limited context, the combination of cannabis and crack deserves more thorough clinical investigation to assess its potential use as a strategy to reduce the damage associated with crack use.

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: subgroup analysis of the DISTINCT randomised trial.

PubMed

Mancia, G; Cha, G; Gil-Extremera, B; Harvey, P; Lewin, A J; Villa, G; Kjeldsen, S E

2017-03-01

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS-Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min -1 , n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy.

Biomechanical analysis of combining head-down tilt traction with vibration for different grades of degeneration of the lumbar spine.

PubMed

Wang, Sicong; Wang, Lizhen; Wang, Yawei; Du, Chengfei; Zhang, Ming; Fan, Yubo

2017-01-01

In recent years, a combination of traction and vibration therapy is usually used to alleviate low back pain (LBP) in clinical settings. Combining head-down tilt (HDT) traction with vibration was demonstrated to be efficacious for LBP patients in our previous study. However, the biomechanics of the lumbar spine during this combined treatment is not well known and need quantitative analysis. In addition, LBP patients have different grades of degeneration of the lumbar spinal structure, which are often age related. Selecting a suitable rehabilitation therapy for different age groups of patients has been challenging. Therefore, a finite element (FE) model of the L1-L5 lumbar spine and a vibration dynamic model are developed in this study in order to investigate the biomechanical effects of the combination of HDT traction and vibration therapy on the age-related degeneration of the lumbar spine. The decrease of intradiscal pressure is more effective when vibration is combined with traction therapy. Moreover, the stresses on the discs are lower in the "traction+vibration" mode than the "traction-only" mode. The stress concentration at the posterior part of nucleus is mitigated after the vibration is combined. The disc deformations especially posterior disc radial retraction is improved in the "traction+vibration" mode. These beneficial effects of this therapy could help decompress the discs and spinal nerves and therefore relieve LBP. Simultaneously, patients with grade 1 degeneration (approximately 41-50 years old) are able to achieve better results compared with other age groups. This study could be used to provide a more effective LBP rehabilitation therapy. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

Combination therapy for erectile dysfunction: an update review.

PubMed

Dhir, Rohit R; Lin, Hao-Cheng; Canfield, Steven E; Wang, Run

2011-05-01

The introduction of oral phosphodiesterase-5 inhibitors (PDE5Is) in the late 1990s and early 2000s revolutionized the field of sexual medicine and PDE5Is are currently first-line monotherapy for erectile dysfunction (ED). However, a significant proportion of patients with complex ED will be therapeutic non-responders to PDE5I monotherapy. Combination therapy has recently been adopted for more refractory cases of ED, but a critical evaluation of current combination therapies is lacking. A thorough PubMed and Cochrane Library search was conducted focusing on the effectiveness of combination therapies for ED in therapeutic non-responders to PDE5I therapy. Journal articles spanning the time period between January 1990 and December 2010 were reviewed. Criteria included all pertinent review articles, randomized controlled trials, cohort studies and retrospective analyses. References from retrieved articles were also manually scanned for additional relevant publications. Published combination therapies include PDE5I plus vacuum erectile device (VED), intraurethral medication, intracavernosal injection (ICI), androgen supplement, α-blocker or miscellaneous combinations. Based on this review, some of these combination treatments appeared to be quite effective in preliminary testing. Caution must be advised, however, as the majority of combination therapy articles in the last decade have numerous limitations including study biases and small subject size. Regardless of limitations, present combination therapy research provides a solid foundation for future studies in complex ED management.

Studying the Effectiveness of Combination Therapy (Based on Executive Function and Sensory Integration) Child-Centered on the Symptoms of Attention Deficit/hyperactivity Disorder (ADHD)

ERIC Educational Resources Information Center

Salami, Fatemeh; Ashayeri, Hassan; Estaki, Mahnaz; Farzad, Valiollah; Entezar, Roya Koochak

2017-01-01

The aim of the present study is to examine the effectiveness of combination therapy based on executive function and sensory integration child-centered on ADHD. For this purpose, from among all first, second and third grade primary school students in Shiraz, 40 children were selected. The selected students were randomly assigned in two groups of…

Anti-proliferative and anti-migration effects of Polish propolis combined with Hypericum perforatum L. on glioblastoma multiforme cell line U87MG.

PubMed

Borawska, Maria H; Naliwajko, Sylwia K; Moskwa, Justyna; Markiewicz-Żukowska, Renata; Puścion-Jakubik, Anna; Soroczyńska, Jolanta

2016-09-20

Propolis and Hypericum perforatum L. are natural products which contain many active compounds and have numerous beneficial effects, including an antitumor effect. Gliobmastoma multiforme (GBM) is a common primary brain tumor with poor prognosis and limited treatment options. In this study, the effect of propolis (EEP) combined with H. perforatum L. (HPE) on glioblastoma cell line U87MG was investigated for the first time. Anti-proliferative activity of EEP, HPE and their combination (EEP + HPE) was determined by a cytotoxicity test, DNA binding by [(3)H]-thymidine incorporation and cell migration assay. Anti-metastatic properties in U87MG treated with EEP, HPE and EEP + HPE were estimated on cells migration test (scratch assay) and metalloproteinases (MMP2 and MMP9) secretion (gelatin zymography). Combination of HPE and EEP extracts was found to have a time- and dose-dependent inhibitory effect on the viability of U87MG cells. This effect was significantly higher (p < 0.05) when compared to these two extracts applied separately, which was confirmed by the significant reduction of DNA synthesis and significantly higher mitochondrial membrane permeabilization. A significant decreasing in migration cells and in pro-MMP9 and pro-MMP2 secretion in U87MG cells were demonstrated after exposure to combination of EEP (30 μg/ml) with HPE (6.25 μg/ml). In this study, the combination of ethanolic extract from propolis and ethanolic extract of fresh-cut H. perforatum L. was proved the ability to reduce invasiveness of glioma cells through the inhibition of MMP2 and MMP9 secretion and suppression of cell migration. It has a more potent anti-proliferative effect on U87MG glioma cell line compared to using propolis and H. perforatum L. separately. Further studies are required to verify whether the examined extracts can activate apoptotic pathways.

Sound waves and antineoplastic drugs: The possibility of an enhanced combined anticancer therapy.

PubMed

Feril, Loreto B; Kondo, Takashi; Umemura, Shin-Ichiro; Tachibana, Katsuro; Manalo, Angelo H; Riesz, Peter

2002-12-01

Kremkau wrote a historical review of the use of ultrasound in cancer therapy in 1979((1)) In 1990, Kondo and Kano published a Japanese review of the implications of the thermal and nonthermal effects of ultrasound in the treatment of cancer(2)). Again in 2000, Kondo et al reviewed the therapeutic applications of ultrasound and shock wave, emphasizing their thermal and cavitational effects(3)). Here we focus on the effects of ultrasound or shock waves in combination with anticancer agents, emphasizing their mechanisms of action and interaction. Most of the studies cited here reported promising results. Although the extent of the augmented combined effects in vivo is limited, synergism is the rule in vitro. In addition to the thermal effect of ultrasound, cavitational effects undoubtedly played a major role in both ultrasound and, more prominently, in shock wave therapy. Although the mechanism of the nonthermal noncavitational effects on biological processes is obscure, several factors, including temperature and the occurrence of cavitation and inertial cavitation, probably coexist and blend with these other effects. Magnification of anticancer activity results mainly from increased localization of drugs or other agents in vivo and increased intracellular permeabilisation both in vivo and in vitro. On the other hand, sublethal damage caused by ultrasound or shock waves may render cells more susceptible, to the effects of the agents, and both may act together, further amplifying these effects. We thus conclude that proper combination of an appropriate agent and ultrasound or shock wave should help improve cancer therapy by minimizing the side effects of drugs by lowering the effective dose and reducing the systemic concentration while increasing the efficiency of the therapy as a whole. Future studies should reveal specific conditions in this combined therapy that will lead to optimal outcome.

The effect of an interactive cycling training on cognitive functioning in older adults with mild dementia: study protocol for a randomized controlled trial.

PubMed

Karssemeijer, E G A; Bossers, W J R; Aaronson, J A; Kessels, R P C; Olde Rikkert, M G M

2017-03-21

To date there is no cure or an effective disease-modifying drug to treat dementia. Available acetylcholine-esterase inhibiting drugs or memantine only produce small benefits on cognitive and behavioural functioning and their clinical relevance remains controversial. Combined cognitive-aerobic interventions are an appealing alternative or add-on to current pharmacological treatments. The primary aim of this study is to investigate the efficacy of a combined cognitive-aerobic training and a single aerobic training compared to an active control group in older adults with mild dementia. We expect to find a beneficial effect on executive functioning in both training regimes, compared to the control intervention, with the largest effect in the combined cognitive-aerobic group. Secondary, intervention effects on cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty and quality of life are studied. The design is a single-blind, randomized controlled trial (RCT) with three groups: a combined cognitive-aerobic bicycle training (interactive cycling), a single aerobic bicycle training and a control intervention, which consists of stretching and toning exercises. Older adults with mild dementia follow a 12-week training program consisting of three training sessions of 30-40 min per week. The primary study outcome is objective executive functioning measured with a neuropsychological assessment. Secondary measures are objective cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty, mood and quality of life. The three groups are compared at baseline, after 6 and 12 weeks of training, and at 24-week follow-up. This study will provide novel information on the effects of an interactive cycling training on executive function in older adults with mild dementia. Furthermore, since this study has both a combined cognitive-aerobic training and a single aerobic training group the effectiveness of the different components of the intervention can be identified. The results of this study may be used for physical and mental activity recommendations in older adults with dementia. The Netherlands National Trial Register NTR5581 . Registered 14 February 2016.

Comparison of opportunities to respond and generation effect as potential causal mechanisms for incremental rehearsal with multiplication combinations.

PubMed

Zaslofsky, Anne F; Scholin, Sarah E; Burns, Matthew K; Varma, Sashank

2016-04-01

Incremental rehearsal (IR) is an intervention with demonstrated effectiveness in increasing retention of information, yet little is known about how specific intervention components contribute to the intervention's effectiveness. The purpose of this study was to further the theoretical understanding of the intervention by comparing the effects of opportunities to respond (OTR) and generation demand on retention of multiplication combinations. Using a between subject 2 × 2 factorial design, 103 4th and 5th grade students were taught seven multiplication combinations using one of four versions of IR that orthogonally varied OTR (high versus low) and generation demands (high versus low). A two-way ANOVA revealed main effects for OTR, generation demands, and an interaction of the two factors. The effect of generation demands was large (d=1.31), whereas the overall effect of OTR was moderate (d=0.66). Critically, the two factors interacted, with the largest learning gains observed when OTR and generation demands were both high. The results of this study suggest that generation demand is an important factor in the effectiveness of rehearsal interventions. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Combination treatment with Rhizoma Paridis and Rhizoma Curcuma longa extracts and 10-hydroxycamptothecin enhances the antitumor effect in H22 tumor model by increasing the plasma concentration.

PubMed

Liu, Zhen; Li, Hongfa; Fan, Yaya; Liu, Yuanxue; Man, Shuli; Yu, Peng; Gao, Wenyuan

2016-10-01

The combination of Western medicine and Chinese prescription is the most effective tumor therapy in China market. In our previous report, a new prescription composed by Rhizoma Paridis and Rhizoma Curcuma longa called LouHuang preparation (LH) shows good antitumor activity. 10-Hydroxycamptothecin (HCPT) as a chemotherapy agent is used for treatment of solid tumors in clinical. In this study, we investigated the combination effect of LH and HCPT on H22 tumor cells in vitro and in vivo. In vitro test, combination of LH and HCPT presented a synergistic effect on H22 cancer cells. Because of the toxicity of HCPT in normal dosage with intraperitoneal injection, we chose a low dose in the study. LH increased the tumor inhibition rate of HCPT in H22 tumor model from 39% to 55% and showed additive effect by the q value method. The concentration of HCPT in plasma was detected by HPLC-FLD method and increased from 60 to 75ng/mL when combined with LH. For the absorption research, LH significantly enhanced the absorption transport of HCPT from 7019.04 to 11569.02ng/cm 2 , while improved the permeation flux (F) and apparent permeability (P app ) of HCPT from 10.62 to 21.47 (ng/cm 2 min) and 9.92-20.07 (10 -6 cm/s), respectively. The study indicates that LH could boost the efficacy of HCPT by increasing the plasma concentration regardless of the formulation and combined administration of HCPT and LH might be used as an adjuvant drug for treatment of liver cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Assessment of early combination effects of colistin and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii in dynamic time-kill experiments.

PubMed

Tängdén, Thomas; Karvanen, Matti; Friberg, Lena E; Odenholt, Inga; Cars, Otto

2017-07-01

In view of the paucity of clinical evidence, in vitro studies are needed to find antibiotic combinations effective against multidrug-resistant Gram-negative bacteria. Interpretation of in vitro effects is usually based on bacterial growth after 24 h in time-kill and checkerboard experiments. However, the clinical relevance of the effects observed in vitro is not established. In this study we explored alternative output parameters to assess the activities of colistin and meropenem against Pseudomonas aeruginosa and Acinetobacter baumannii. Four strains each of P. aeruginosa and A. baumannii were exposed to colistin and meropenem, alone and in combination, in 8 h dynamic time-kill experiments. Initial (1 h), maximum and 8 h bacterial reductions and the area under the bacterial time-kill curve were evaluated. Checkerboards, interpreted based on fractional inhibitory concentration indices after 24 h, were performed for comparison. In the time-kill experiments, the combination resulted in enhanced 1 h, maximum and 8 h bacterial reductions against 2, 3 and 5 of 8 strains, respectively, as compared to the single drugs. A statistically significant reduction in the area under the time-kill curve was observed for three strains. In contrast, the checkerboards did not identify synergy for any of the strains. Combination effects were frequently found with colistin and meropenem against P. aeruginosa and A. baumannii in time-kill experiments but were not detected with the checkerboard method. We propose that the early dynamics of bacterial killing and growth, which may be of great clinical importance, should be considered in future in vitro combination studies.

Interactions between rewarding lateral hypothalamic and aversive nucleus reticularis gigantocellularis stimulation.

PubMed

Diotte, M; Miguelez, M; Miliaressis, E; Bielajew, C

2000-12-05

The interaction between rewarding and aversive consequences of brain stimulation were assessed in two studies. In the first, the frequency threshold for 300 ms trains of combined lateral hypothalamic (LH) and nucleus reticularis gigantocellularis (Gi) stimulation, in which each LH pulse was followed 2 ms later by the Gi one, was determined for one month. Compared to the threshold for trains of single LH pulses, combined LH-Gi stimulation initially increased the frequency threshold; however, this effect reversed within one session and was subsequently maintained for the duration of the study. The aversion produced by Gi stimulation, as measured by latency to escape, was abolished following a single session of LH-Gi pairs. In the second study, a subset of animals received both presentations of combined pulses, LH followed by Gi, and the reverse; the interval between pulses was varied from 0.2 to 6.4 ms. The effectiveness of combined stimulation, determined by the ratio of LH frequency thresholds to that of the LH-Gi ranged from 0 to 50% across animals but the individual effectiveness functions within animals did not vary with different intervals. In addition, the order of presentation of pulses was of no consequence. Thus, not only did exposure to LH stimulation appear to obliterate Gi aversion, but the combination of LH and Gi pulses added to the rewarding effect produced by LH stimulation alone.

Neuroprotective effects of phytocannabinoid-based medicines in experimental models of Huntington's disease.

PubMed

Sagredo, Onintza; Pazos, M Ruth; Satta, Valentina; Ramos, José A; Pertwee, Roger G; Fernández-Ruiz, Javier

2011-09-01

We studied whether combinations of botanical extracts enriched in either Δ(9)-tetrahydrocannabinol (Δ(9)-THC) or cannabidiol (CBD), which are the main constituents of the cannabis-based medicine Sativex, provide neuroprotection in rat models of Huntington's disease (HD). We used rats intoxicated with 3-nitropropionate (3NP) that were given combinations of Δ(9)-THC- and CBD-enriched botanical extracts. The issue was also studied in malonate-lesioned rats. The administration of Δ(9)-THC- and CBD-enriched botanical extracts combined in a ratio of 1:1 as in Sativex attenuated 3NP-induced GABA deficiency, loss of Nissl-stained neurons, down-regulation of CB(1) receptor and IGF-1 expression, and up-regulation of calpain expression, whereas it completely reversed the reduction in superoxide dismutase-1 expression. Similar responses were generally found with other combinations of Δ(9)-THC- and CBD-enriched botanical extracts, suggesting that these effects are probably related to the antioxidant and CB(1) and CB(2) receptor-independent properties of both phytocannabinoids. In fact, selective antagonists for both receptor types, i.e., SR141716 and AM630, respectively, were unable to prevent the positive effects on calpain expression caused in 3NP-intoxicated rats by the 1:1 combination of Δ(9)-THC and CBD. Finally, this combination also reversed the up-regulation of proinflammatory markers such as inducible nitric oxide synthase observed in malonate-lesioned rats. In conclusion, this study provides preclinical evidence in support of a beneficial effect of the cannabis-based medicine Sativex as a neuroprotective agent capable of delaying disease progression in HD, a disorder that is currently poorly managed in the clinic, prompting an urgent need for clinical trials with agents showing positive results in preclinical studies. Copyright © 2011 Wiley-Liss, Inc.

Evidence for the efficacy and safety of tadalafil and finasteride in combination for the treatment of lower urinary tract symptoms and erectile dysfunction in men with benign prostatic hyperplasia

PubMed Central

Olesovsky, Chris; Kapoor, Anil

2016-01-01

Benign prostatic hyperplasia (BPH) is an age-related phenomenon associated with prostatic enlargement and bladder outlet obstruction that can cause significant lower urinary tract symptoms (LUTS). These LUTS have a negative impact on an individual’s quality of life, which is why treatment of symptomatic BPH has become a major priority. Although surgical interventions exist for treating BPH, pharmacological therapies are often preferred due to their minimal invasiveness and high degree of effectiveness. The three classes of drugs approved for treating BPH include α-blockers, 5-α-reductase inhibitors (5-ARIs) and phosphodiesterase 5 (PDE-5) inhibitors. Individually, each class of drug has been studied and shown to improve symptom relief through a variety of different mechanisms. A more recent focus has been on the development of combinatorial therapies that combine classes of drugs in order to provide maximal benefit. The mTOPS and CombAT studies were the first of their kind to examine whether the combination of 5-ARIs and α-blockers was more effective than monotherapy alone. Both studies found similar results in that the combinatorial therapy was superior to monotherapy. Over the last decade other combinatorial therapies have been at the forefront of investigation. One in particular is the combination of tadalafil, a PDE-5 inhibitor, with finasteride, a 5-ARI. Studies have shown that the combination of tadalafil and finasteride is a safe, effective, and well tolerated treatment for BPH. Evidence suggests that this combination may be particularly effective in reducing treatment-related sexual adverse events associated with 5-ARI treatments. The following review will explore in detail the current evidence surrounding treatment of BPH LUTS using tadalafil and finasteride. PMID:27928428

Cost-effectiveness analysis: controlled-release nifedipine and valsartan combination therapy in patients with essential hypertension: the adalat CR and valsartan cost-effectiveness combination (ADVANCE-Combi) study.

PubMed

Saito, Ikuo; Fujikawa, Keita; Saruta, Takao

2008-07-01

As recommended by the guidelines such as JSH 2004, combination therapy with multiple agents is now being applied to many patients with hypertension. However, a pharmacoeconomic analysis of each therapy has not been fully undertaken in Japan, despite increasing societal interest. In this study, the cost-effectiveness of two calcium channel blockers, each coadministered with an angiotensin receptor blockade, was compared using data from the ADVANCE-Combi study. The ADVANCE-Combi study was a 16-week double-blind, randomized clinical trial to compare the efficacy and safety of two combination therapies (controlled-release nifedipine [nifedipine CR] plus valsartan vs. amlodipine plus valsartan) on blood pressure (BP) control in patients with moderate to severe essential hypertension. The incremental cost effectiveness of each cohort was compared from the perspective of insurers. The average total cost per patient was Japanese yen (JPY) 31,615 for the nifedipine CR treatment group and JPY 35,399 for the amlodipine treatment group (p < 0.001). The achievement rate of the target BP (SBP/DBP < 130/85 mmHg for patients aged under 60 years; SBP/DBP < 140/90 mmHg for those aged 60 years and over) was significantly higher in the nifedipine CR treatment group (61.2%) than in the amlodipine treatment group (34.6%) (p < 0.001), with no difference in the incidence of drug-related adverse events. Accordingly, the base case economic analysis demonstrated that the nifedipine CR treatment group was dominant (more efficacious and less costly) to the amlodipine treatment group. This result was supported by univariate and probabilistic sensitivity analyses. These results indicate that nifedipine CR-based combination therapy is superior to amlodipine-based combination therapy for the management of essential hypertension in the Japanese population.

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia.

PubMed

Lei, Guang-Sheng; Zhang, Chen; Zimmerman, Michelle K; Lee, Chao-Hung

2015-12-14

The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4(+) cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11b(low) CD11c(high) alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Synergistic Effect of Curcumin in Combination with Anticancer Agents in Human Retinoblastoma Cancer Cell Lines.

PubMed

Sreenivasan, Seethalakshmi; Krishnakumar, Subramanian

2015-01-01

Curcumin (diferuloylmethane), a phenolic compound obtained from the rhizome of the herb Curcuma longa, is known to have anti-proliferative and anti-tumor properties. In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line. A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive. We also performed the apoptosis and cell-cycle kinetics study with single drugs in combination with curcumin in a human RB cell lines (Y79 and Weri-Rb1). Curcumin caused concentration-dependent decrease in cell proliferation, cell kinetics, and also induced apoptosis in both the RB cell lines. When combination of curcumin with individual drugs like carboplatin or etoposide or vincristine was treated on to RB cells, both cell viability and cell cycling were reduced and increased apoptosis was noted, in comparison with single drug treatment. These effects were significant in both the cell lines, indicating the ability of curcumin to increase the sensitivity of RB cells to chemotherapy drugs. Our in vitro findings showed that the combination of curcumin with single drug treatment showed marked synergistic inhibitory effect against RB cell lines. These results suggest that curcumin can be used as a modulator which may have a potential therapeutic value for the treatment of RB cancer patients.

[Sensitivity of clinical Proteus strains to antibiotics and their combinations].

PubMed

Sheina, E P; Arutcheva, A A

1978-05-01

In 1976 isolation of Proteus from wounds of patients with various purulent processes amounted to 14.5 per cent. Serotypes 0-10, 0-3 and H-3 predominated among the isolates. Sensitivity of 35 clinical strains of Proteus to 10 antibiotics, furagin and nevigramone was studied by the method of serial dilutions in liquid media. All the isolates were highly resistant to the antibiotics except gentamicin, furagin and nevigramone, the MIC of which for most of the strains was 3.12, 1.6-3.12 and 6.25-12.5 gamma/ml, respectively. The effect of 14 combinations of chemotherapeutics was also studied. The combinations of gentamicin with carbenicillin, gentamicin with ampicillin and monomycin with ampicillin proved to be most effective against the Proteus strains tested. The following combinations may be of practical value: monomycin + carbenicillin, kanamycin + ampicillin, kanamycin + carbenicillin, ampicillin + furagin, gentamicin + nevigramone. The combinations of carbenicillin with furagin and gentamicin with furagin were also rational.

Teaching graphic symbol combinations to children with limited speech during shared story reading.

PubMed

Tönsing, Kerstin M; Dada, Shakila; Alant, Erna

2014-12-01

The aim of this study was to determine the effect of an intervention strategy on the production of graphic symbol combinations in children with limited speech. Four children between the ages of 6;5 and 10;8 (years;months) with limited speech participated in the study. A single-subject, multiple probe design across three different types of semantic relations was used. Generalization to untrained exemplars was also monitored. Results were mixed across the four participants: two participants learned to combine symbols across different types of relations, maintained these skills post intervention, and generalized their skills to untrained combinations; and two participants showed less consistent evidence of learning. The effects, as measured during structured probes, were strong for one participant, moderate for another, and inconclusive for the two others. Responses during shared story reading suggested that the measurement probes might have underestimated participants' ability to combine symbols.

Separate and combined effects of the cannabinoid agonists nabilone and Δ⁹-THC in humans discriminating Δ⁹-THC.

PubMed

Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

2011-07-01

Agonist replacement treatment is a promising strategy to manage cannabis-use disorders. The aim of this study was to assess the combined effects of the synthetic cannabinoid agonist nabilone and Δ⁹-tetrahydrocannabinol (Δ⁹-THC) using drug-discrimination procedures, which are sensitive to drug interactions. Testing the concurrent administration of nabilone and Δ⁹-THC was also conducted to provide initial safety and tolerability data, which is important because cannabis users will likely lapse during treatment. Six cannabis users learned to discriminate 30 mg oral Δ⁹-THC from placebo and then received nabilone (0, 1 and 3mg) and Δ⁹-THC (0, 5, 15 and 30 mg), alone and in combination. Subjects completed the multiple-choice procedure to assess drug reinforcement, and self-report, task performance and physiological measures were collected. Δ⁹-THC and nabilone alone shared discriminative-stimulus effects with the training dose of Δ⁹-THC, increased crossover point on the multiple-choice procedure, produced overlapping subject ratings and decreased skin temperature. Nabilone alone also elevated heart rate. In combination, nabilone shifted the discriminative-stimulus effects of Δ⁹-THC leftward/upward and enhanced Δ⁹-THC effects on the other outcome measures. These results replicate a previous study demonstrating that nabilone shares agonist effects with the active constituent of cannabis in cannabis users, and contribute further by indicating that nabilone would likely be safe and well tolerated when combined with cannabis. These data support the conduct of future studies to determine if nabilone treatment would produce cross-tolerance to the abuse-related effects of cannabis and reduce cannabis use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway.

PubMed

Wu, Jun; Yu, Junxian; Wang, Jing; Zhang, Chenguang; Shang, Kun; Yao, Xiaojun; Cao, Bangwei

2018-04-01

Apatinib has been proved effective in the treatment of advanced gastric cancer. Traditional Chinese medicine is often considered as adjuvants which could increase the effects and counteract the side effects of chemotherapy. The present study aims to explore the antitumor effects of Astragalus polysaccharide (AsPs) in combination with Apatinib in gastric cancer AGS cells. Our results demonstrated that the expression of VEGFR-2 was observed in human gastric cancer line AGS. Both Apatinib and AsPs could significantly inhibit the proliferation of AGS cells in a dose-dependent manner and Apatinib in combination with AsPs showed enhanced inhibitory effects on cell proliferation, migration and invasion compared with Apatinib monotherapy. Moreover, there was a remarkable increase in apoptosis following Apatinib treatment which could be enhanced by the addition of AsPs. Western blotting showed that the combination of Apatinib and AsPs could inhibit the expression of phosphorylated AKT (p-AKT) and MMP-9 expression. In addition, both Apatinib alone and Apatinib in combination with AsPs induced celluar autophagy which could be attenuated by the autophagy inhibitor 3-MA. The suppression of autophagy leaded to further apoptosis induction and cell proliferation suppression. In conclusion, the current study showed AsPs enhanced antitumor effects of Apatinib on AGS cells by the mechanism which includes inhibition of AKT signaling pathway. Apatinib-induced autophagy could be attenuated by 3-MA, which subsequently increased the apoptosis rate. On the basis of our study, the combination of Apatinib and AsPs could be considered as a potential candidate in the gastric cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

A Combination of Resveratrol and Curcumin is Effective Against Aluminum Chloride-Induced Neuroinflammation in Rats.

PubMed

Zaky, Amira; Bassiouny, Ahmad; Farghaly, Mahitab; El-Sabaa, Bassma M

2017-01-01

Experimental studies have demonstrated that aluminum is an environmental toxin that induces neuroinflammation and the development of Alzheimer's disease. In this report, we investigated the beneficial effect of a combination of resveratrol and curcumin to reduce aluminum-induced neuroinflammation. We employed both an in vivo model of aluminum-induced neuroinflammation and an in vitro aluminum stimulated cultured PC-12 cells. Neuroinflammation in rats was assessed by measuring the expression of β-secretase, amyloid-β protein precursor, and γ-subunits (PS-1 and PS-2), along with the inflammatory COX-2, Il-1β, Il-1α, and TNF-α. Furthermore, we measured the expression profiles of neuro-protective Apurinic/apyrimidinic endonuclease 1 (APE1) protein and let-7c microRNA. In parallel, PC-12 cells were treated with 0.5 mM aluminum to induce a neuroinflammation-like state. In addition, curcumin effect, as a selective COX-2 expression inhibitor, was detected in a time course manner. An overall significant attenuation of the inflammatory markers, as well as a decrease in the amyloidogenic mediators, was observed in resveratrol-curcumin treated rats. The therapeutic effect was also confirmed by transmission electron microscopic analysis of the brain cortexes. APE1 was significantly induced by resveratrol-curcumin combination. Both in vivo and in vitro studies indicated that Let-7c expression is significantly reduced after aluminum stimulation, an effect that was partially suppressed by co-addition of either resveratrol or curcumin and totally restored to the normal level by their combination. The present study clearly indicates the synergistic and therapeutic effect of a  resveratrol-curcumin combination. We also show that both compounds exert beneficial effect either cooperatively or through differential molecular mechanisms in counteracting aluminum-induced neuroinflammation.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice.

PubMed

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Diabetes mellitus is the most rampant metabolic pandemic of the 21(st) century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14(th) and 28(th) day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin.

Cellular Effect of Curcumin and Citral Combination on Breast Cancer Cells: Induction of Apoptosis and Cell Cycle Arrest.

PubMed

Patel, Pinaki B; Thakkar, Vasudev R; Patel, Jagdish S

2015-09-01

The unmanageable side effects caused by current chemotherapy regimens to treat cancer are an unresolved problem. Although many phytonutrients are useful as chemoprevention without side effects, their effects are slower and smaller than conventional chemotherapy. In the present work, we examined the cumulative effect of two phytonutrients, curcumin and citral, on breast cancer cell lines and compared their effect with the known chemotherapy regimen of cyclophosphamide, methotrexate, and 5-fluorouracil. Using cultured breast cancer and normal epithelial cells, the cytotoxic and apoptotic effect of curcumin and citral was evaluated in vitro. The synergistic effect of curcumin and citral was calculated by a combination index study using the method by Chou and Talalay. Cell death pathways and mechanisms were analyzed by measuring intracellular reactive oxygen species (ROS) and apoptotic protein levels. Curcumin and citral caused dose and time dependent cell death and showed a synergistic effect at effective concentration EC50 and above concentrations in breast cancer cells without disturbing normal breast epithelial cells. With combination curcumin and citral treatment, apoptosis induction and cell cycle arrest at G0/G1 phase in breast cancer cells were observed. Curcumin and citral generated ROS and activated p53 and poly (ADP-ribose) polymerase-1 mediated apoptotic pathways. The results of this study suggest that curcumin and citral in combination may be a useful therapeutic intervention for breast cancer.

Inhibitory effect and mechanism of acarbose combined with gymnemic acid on maltose absorption in rat intestine

PubMed Central

Luo, Hong; Wang, Le Feng; Imoto, Toshiaki; Hiji, Yasutake

2001-01-01

AIM: To compare the combinative and individual effect of acarbose and gymnemic acid (GA) on maltose absorption and hydrolysis in small intestine to determine whether nutrient control in diabetic care can be improved by combination of them. METHODS: The absorption and hydrolysis of maltose were studied by cyclic perfusion of intestinal loops in situ and motility of the intestine was recorded with the intestinal ring in vitro using Wistar rats. RESULTS: The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 g/L-1.0 g/L) and acarbose (0.1 mmol/L-2.0 mmol/L) throughout their effective duration (P < 0.05, U test of Mann-Whitney), although the improvement only could be seen at a low dosage during the first hour. With the combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 h and the inhibitory effect onset of GA was fastened to 15 min. GA suppressed the intestinal mobility with a good correlation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of 2 mmol/L (high dose) acarbose on maltose hydrolysis was dual modulated by 1 g/L GA in vivo indicating that the combined effects involved the functional alteration of intestinal barriers. CONCLUSION: There are augmented effects of acarbose and GA, which involve pre-cellular and paracellular barriers. Diabetic care can be improved by employing the combination. PMID:11819725

Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

PubMed

Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

1980-01-01

The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

Propagation of coherently combined truncated laser beam arrays with beam distortions in non-Kolmogorov turbulence.

PubMed

Tao, Rumao; Si, Lei; Ma, Yanxing; Zhou, Pu; Liu, Zejin

2012-08-10

The propagation properties of coherently combined truncated laser beam arrays with beam distortions through non-Kolmogorov turbulence are studied in detail both analytically and numerically. The analytical expressions for the average intensity and the beam width of coherently combined truncated laser beam arrays with beam distortions propagating through turbulence are derived based on the combination of statistical optics methods and the extended Huygens-Fresnel principle. The effect of beam distortions, such as amplitude modulation and phase fluctuation, is studied by numerical examples. The numerical results reveal that phase fluctuations have significant influence on the spreading of coherently combined truncated laser beam arrays in non-Kolmogorov turbulence, and the effects of the phase fluctuations can be negligible as long as the phase fluctuations are controlled under a certain level, i.e., a>0.05 for the situation considered in the paper. Furthermore, large phase fluctuations can convert the beam distribution rapidly to a Gaussian form, vary the spreading, weaken the optimum truncation effects, and suppress the dependence of spreading on the parameters of the non-Kolmogorov turbulence.

In-vitro and in-vivo inhibition of melanoma growth and metastasis by the drug combination of celecoxib and dacarbazine.

PubMed

Sadhu, Satya S; Wang, Shenggang; Averineni, Ranjith K; Seefeldt, Teresa; Yang, Yang; Guan, Xiangming

2016-12-01

Celecoxib has been found to be effective in cancer prevention and treatment. Its combination with other chemotherapeutic agents was reported to produce synergistic/additive effects on various cancers. Dacarbazine (DTIC) is one of the most commonly used drugs in the treatment of metastatic melanoma. This investigation aimed to determine the in-vitro and in-vivo effects of the drug combination of celecoxib and DTIC on melanoma growth and metastasis. Melanoma cells B16-F10 and SK-MEL-28, and female C57BL/6 mice were used for the study. Our in-vitro data showed that significant synergistic effects were obtained when celecoxib was used together with various concentrations of DTIC. A study with B16-F10 cells using flow cytometry analysis showed that the drug combination induced significantly more apoptosis than each drug used individually. Our in-vivo results showed that the drug combination was much more effective than each drug used alone for the inhibition of both melanoma growth and metastasis in the B16-F10+C57BL/6 mouse models. For melanoma growth, the median survival rates for phosphate-buffered saline (PBS) (control), celecoxib (30 mg/kg), DTIC-1 (10 mg/kg), DTIC-2 (positive control, 50 mg/kg), and the drug combination (DTIC 10 mg/kg+celecoxib 30 mg/kg) were 6, 6.5, 7.5, 7.5, and 9 days, respectively. For melanoma metastasis, the average number of metastatic tumors in murine lungs was 53.7±10.7, 31.8±18.6, 21.2±21.7, 7.0±9.0, and 0.8±2.0 for PBS, DTIC-1, celecoxib, the drug combination, and DTIC-2. Our results warrant further investigation of the combination as an effective treatment for melanoma patients.

Novel biomolecule lycopene-reduced graphene oxide-silver nanoparticle enhances apoptotic potential of trichostatin A in human ovarian cancer cells (SKOV3)

PubMed Central

Zhang, Xi-Feng; Huang, Feng-Hua; Zhang, Guo-Liang; Bai, Ding-Ping; Massimo, De Felici; Huang, Yi-Fan; Gurunathan, Sangiliyandi

2017-01-01

Background Recently, there has been much interest in the field of nanomedicine to improve prevention, diagnosis, and treatment. Combination therapy seems to be most effective when two different molecules that work by different mechanisms are combined at low dose, thereby decreasing the possibility of drug resistance and occurrence of unbearable side effects. Based on this consideration, the study was designed to investigate the combination effect of reduced graphene oxide-silver nanoparticles (rGO-AgNPs) and trichostatin A (TSA) in human ovarian cancer cells (SKOV3). Methods The rGO-AgNPs were synthesized using a biomolecule called lycopene, and the resultant product was characterized by various analytical techniques. The combination effect of rGO-Ag and TSA was investigated in SKOV3 cells using various cellular assays such as cell viability, cytotoxicity, and immunofluorescence analysis. Results AgNPs were uniformly distributed on the surface of graphene sheet with an average size between 10 and 50 nm. rGO-Ag and TSA were found to inhibit cell viability in a dose-dependent manner. The combination of rGO-Ag and TSA at low concentration showed a significant effect on cell viability, and increased cytotoxicity by increasing the level of malondialdehyde and decreasing the level of glutathione, and also causing mitochondrial dysfunction. Furthermore, the combination of rGO-Ag and TSA had a more pronounced effect on DNA fragmentation and double-strand breaks, and eventually induced apoptosis. Conclusion This study is the first to report that the combination of rGO-Ag and TSA can cause potential cytotoxicity and also induce significantly greater cell death compared to either rGO-Ag alone or TSA alone in SKOV3 cells by various mechanisms including reactive oxygen species generation, mitochondrial dysfunction, and DNA damage. Therefore, this combination chemotherapy could be possibly used in advanced cancers that are not suitable for radiation therapy or surgical treatment and facilitate overcoming tumor resistance and disease progression. PMID:29075115

[Effect of ginseng rare ginsenoside components combined with paclitaxel on A549 lung cancer].

PubMed

Yang, Lei; Zhang, Zhen-Hai; Jia, Xiao-Bin

2018-04-01

Traditional Chinese medicine combined with anticancer drugs is a new direction of clinical cancer therapy in recent years. In this study, the optimal ratio of ginseng rare ginsenoside components and paclitaxel was optimized by MTT method, and the proliferative, apoptotic and anti-tumor effects of lung cancer A549 cells were investigated. It was found that the inhibitory effect on the proliferation of lung cancer A549 cells was the same as that on paclitaxel when the ratio of rare ginseng rare ginsenoside components to paclitaxel was 4∶6. Further studies showed that the combined therapy significantly increased the inductive effect of apoptosis in A549 cells, and up-regulated the expression of caspase-3 protein and down-regulated the ratio of Bcl-2/Bax. The tumor-bearing mice model showed that the combination therapy of ginseng rare ginsenoside components and paclitaxel could significantly inhibit the growth of tumor and alleviate the toxic and side effects of paclitaxel on liver. A multi-component system of ginseng rare ginsenoside components-paclitaxel was established in this paper. The proliferation and growth of lung cancer A549 cells were inhibited by paclitaxel-induced apoptosis, the dosage of paclitaxel and the toxicity of paclitaxel were reduced, and the effect of anti-lung cancer was enhanced, which provided a theoretical basis for later studies and clinical application. Copyright© by the Chinese Pharmaceutical Association.

Chemical combination effects predict connectivity in biological systems

PubMed Central

Lehár, Joseph; Zimmermann, Grant R; Krueger, Andrew S; Molnar, Raymond A; Ledell, Jebediah T; Heilbut, Adrian M; Short, Glenn F; Giusti, Leanne C; Nolan, Garry P; Magid, Omar A; Lee, Margaret S; Borisy, Alexis A; Stockwell, Brent R; Keith, Curtis T

2007-01-01

Efforts to construct therapeutically useful models of biological systems require large and diverse sets of data on functional connections between their components. Here we show that cellular responses to combinations of chemicals reveal how their biological targets are connected. Simulations of pathways with pairs of inhibitors at varying doses predict distinct response surface shapes that are reproduced in a yeast experiment, with further support from a larger screen using human tumour cells. The response morphology yields detailed connectivity constraints between nearby targets, and synergy profiles across many combinations show relatedness between targets in the whole network. Constraints from chemical combinations complement genetic studies, because they probe different cellular components and can be applied to disease models that are not amenable to mutagenesis. Chemical probes also offer increased flexibility, as they can be continuously dosed, temporally controlled, and readily combined. After extending this initial study to cover a wider range of combination effects and pathway topologies, chemical combinations may be used to refine network models or to identify novel targets. This response surface methodology may even apply to non-biological systems where responses to targeted perturbations can be measured. PMID:17332758

Gestrinone combined with ultrasound-guided aspiration and ethanol injection for treatment of chocolate cyst of ovary.

PubMed

Wu, Xiaoyun; Xu, Yun

2015-05-01

The aim of this study was to determine clinical performance of gestrinone combined with ultrasound-guided aspiration and ethanol injection in treating chocolate cyst of ovary. Sixty-eight patients enrolled in this study were randomly divided into two groups: control group and combination treatment group. In the control group, 34 patients were treated with ultrasound-guided aspiration and ethanol injection. In the combination treatment group, 34 patients received gestrinone p.o. following ultrasound-guided aspiration and ethanol injection. The recurrence rate of chocolate cyst was 10-fold lower in the combination treatment group (2.94%, 1/34) than in the control group (29.4%, 10/34) at 12 months. The effective rate for reduction of chocolate cyst was significantly higher in the combination treatment group (94.12%, 32/34) than in the control group (64.71%, 22/34) (P = 0.009). Gestrinone combined with ultrasound-guided aspiration and ethanol injection therapy is an effective treatment for ovarian chocolate cyst with low recurrence rate. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

The anti-HER3 antibody in combination with trastuzumab exerts synergistic antitumor activity in HER2-positive gastric cancer.

PubMed

Wang, Qiwei; Zhang, Xiaotian; Shen, Enyun; Gao, Jing; Cao, Fengqi; Wang, Xiaojuan; Li, Yilin; Tian, Tiantian; Wang, Jingyuan; Chen, Zuhua; Wang, Jiayuan; Shen, Lin

2016-09-28

The anti-HER2 monoclonal antibody trastuzumab is central to the treatment of HER2-positive gastric cancer (GC); however, its responses are limited. HER3 seems to be the preferred dimerization partner with HER2 and is emerging as a key target for complete blockade of downstream pathways and better clinical response. In this study, we report that novel anti-HER3 antibodies (1A5-3D4) that can neutralize multiple modes of HER3 activation, combined with trastuzumab, exhibited synergistic inhibitory effect on the cell proliferation in HER2-positive GC cell lines. Follow-up studies revealed that the combination treatment significantly inhibited phosphorylation of HER3 as well as AKT and ERK signals. In vivo experiments further showed that the anti-tumor effect of trastuzumab was enhanced by its combination with 1A5-3D4 in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. 1A5-3D4 in combination with trastuzumab exhibits a synergistic inhibitory effect on tumor activity, suggesting that targeting both HER2 and HER3 resulted in an improved treatment effects on HER2-positive GC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effective return-to-work interventions after acquired brain injury: A systematic review.

PubMed

Donker-Cools, Birgit H P M; Daams, Joost G; Wind, Haije; Frings-Dresen, Monique H W

2016-01-01

To gather knowledge about effective return-to-work (RTW) interventions for patients with acquired brain injury (ABI). A database search was performed in PubMed, EMBASE, PsycINFO, CINAHL and the Cochrane Library using keywords and Medical Subject Headings. Studies were included if they met inclusion criteria: adult patients with non-progressive ABI, working pre-injury and an intervention principally designed to improve RTW as an outcome. The methodological quality of included studies was determined and evidence was assessed qualitatively. Twelve studies were included, of which five were randomized controlled trials and seven were cohort studies. Nine studies had sufficient methodological quality. There is strong evidence that work-directed interventions in combination with education/coaching are effective regarding RTW and there are indicative findings for the effectiveness of work-directed interventions in combination with skills training and education/coaching. Reported components of the most effective interventions were tailored approach, early intervention, involvement of patient and employer, work or workplace accommodations, work practice and training of social and work-related skills, including coping and emotional support. Effective RTW interventions for patients with ABI are a combination of work-directed interventions, coaching/education and/or skills training. These interventions have the potential to facilitate sustained RTW for patients with ABI.

The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States.

PubMed

Adamson, Blythe J S; Carlson, Josh J; Kublin, James G; Garrison, Louis P

2017-05-24

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value.

Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on food intake and glycemia in rats.

PubMed

Loi, Barbara; Fantini, Noemi; Colombo, Giancarlo; Gessa, Gian Luigi; Riva, Antonella; Bombardelli, Ezio; Morazzoni, Paolo; Carai, Mauro A M

2013-02-01

Extracts from Phaseolus vulgaris and Cynara scolymus may reduce food intake and/or postprandial glycemia. This study investigated the effect of standardized extracts of P. vulgaris and C. scolymus and their combination on food intake and glycemia in rats. P. vulgaris and C. scolymus extracts, and their 1:2 combination, were administered acutely to rats (a) given access to regular food and water, (b) given access to regular food, water, and a chocolate-flavored beverage, or (c) infused with a starch bolus. P. vulgaris extract and the combination produced comparable reductions in intake of regular food and chocolate-flavored beverage; conversely, C. scolymus extract was ineffective on both parameters. P. vulgaris and C. scolymus extracts additively contributed to the reducing effect of the combination on glycemic rise. These results suggest that a mixture of P. vulgaris and C. scolymus extracts is preferable over each single extract, as it combines the anorectic effect of the P. vulgaris extract with the hypoglycemic effect of both extracts. These data support the recent clinical use of the combination of P. vulgaris and C. scolymus extracts in the control of appetite, food intake, and postprandial glycemia and represent a successful example of translational research in the nutraceutical field. Copyright © 2012 John Wiley & Sons, Ltd.

The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States

PubMed Central

Adamson, Blythe J. S.; Carlson, Josh J.; Kublin, James G.; Garrison, Louis P.

2017-01-01

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value. PMID:28538691

Exploring the relationship between cognitive illness representations and poor emotional health and their combined association with diabetes self-care. A systematic review with meta-analysis.

PubMed

Hudson, Joanna L; Bundy, Chris; Coventry, Peter A; Dickens, Chris

2014-04-01

Depression and anxiety are common in diabetes and are associated with lower diabetes self-care adherence. How this occurs is unclear. Our systematic review explored the relationship between cognitive illness representations and poor emotional health and their combined association with diabetes self-care. Medline, Psycinfo, EMBASE, and CINAHL were searched from inception to June 2013. Data on associations between cognitive illness representations, poor emotional health, and diabetes self-care were extracted. Random effects meta-analysis was used to test the relationship between cognitive illness representations and poor emotional health. Their combined effect on diabetes self-care was narratively evaluated. Nine cross-sectional studies were included. Increased timeline cyclical, consequences, and seriousness beliefs were associated with poorer emotional health symptoms. Lower perceived personal control was associated with increased depression and anxiety, but not mixed anxiety and depressive symptoms. Remaining cognitive illness representation domains had mixed statistically significant and non-significant relationships across emotional states or were measured only once. Effect sizes ranged from small to large (r=±0.20 to 0.51). Two studies explored the combined effects of cognitions and emotions on diabetes self-care. Both showed that cognitive illness representations have an independent effect on diabetes self-care, but only one study found that depression has an independent effect also. Associations between cognitive illness representations and poor emotional health were in the expected direction - negative diabetes perceptions were associated with poorer emotional health. Few studies examined the relative effects of cognitions and emotions on diabetes self-care. Longitudinal studies are needed to clarify directional pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Applying Emax model and bivariate thin plate splines to assess drug interactions

PubMed Central

Kong, Maiying; Lee, J. Jack

2014-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95% point-wise confidence interval as well as its 95% simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies. PMID:20036878

Applying Emax model and bivariate thin plate splines to assess drug interactions.

PubMed

Kong, Maiying; Lee, J Jack

2010-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95 per cent point-wise confidence interval as well as its 95 per cent simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies.

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions

PubMed Central

McNicholl, Janet M.

2016-01-01

ABSTRACT Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention. PMID:27679928

Combining biomedical preventions for HIV: Vaccines with pre-exposure prophylaxis, microbicides or other HIV preventions.

PubMed

McNicholl, Janet M

2016-12-01

Biomedical preventions for HIV, such as vaccines, microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, can each only partially prevent HIV-1 infection in most human trials. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions (CBP) an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective. When licensed, first generation HIV vaccines are likely to be partially effective. Individuals at risk for HIV may receive an HIV vaccine combined with other biomedical preventions, in series or in parallel, in clinical trials or as part of standard of care, with the goal of maximally increasing HIV prevention. In human studies, it is challenging to determine which preventions are best combined, how they interact and how effective they are. Animal models can determine CBP efficacy, whether additive or synergistic, the efficacy of different products and combinations, dose, timing and mechanisms. CBP studies in macaques have shown that partially or minimally effective candidate HIV vaccines combined with partially effective oral PrEP, vaginal PrEP or microbicide generally provided greater protection than either prevention alone against SIV or SHIV challenges. Since human CBP trials will be complex, animal models can guide their design, sample size, endpoints, correlates and surrogates of protection. This review focuses on animal studies and human models of CBP and discusses implications for HIV prevention.

Ginseng and Anticancer Drug Combination to Improve Cancer Chemotherapy: A Critical Review

PubMed Central

Chen, Shihong; Huang, Ying; O'Barr, Stephen A.; Wong, Rebecca A.; Chow, Moses Sing Sum

2014-01-01

Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer. PMID:24876866

Combination Chemoprevention with Grape Antioxidants

PubMed Central

Singh, Chandra K.; Siddiqui, Imtiaz A.; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

2016-01-01

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well-studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape-ingredients alone or together with other agents could impart ‘additive synergism’ against cancer. PMID:26829056

Combination chemoprevention with grape antioxidants.

PubMed

Singh, Chandra K; Siddiqui, Imtiaz A; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

2016-06-01

Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The effect of tuning ankle foot orthoses-footwear combination on the gait parameters of children with cerebral palsy.

PubMed

Eddison, Nicola; Chockalingam, Nachiappan

2013-04-01

There are a wide variety of ankle foot orthoses used in clinical practice which are characterised by their design, the material used and the stiffness of that material. Changing any of these three components will alter the effect of the ankle foot orthosis on gait. The purpose of this article is to provide an overview on the available research on ankle foot orthosis-footwear combination tuning on the gait characteristics of children with cerebral palsy through a structured review. Literature review. A thorough search of previous studies published in English was conducted within all major databases using relevant phrases without any limits for the dates. These searches were then supplemented by tracking all key references from the appropriate articles identified including hand searching of published books where relevant. To date, there are 947 papers in the literature pertaining to the study of ankle foot orthosis. Of these, 153 investigated the use of ankle foot orthosis for children with cerebral palsy. All the studies included in this review were of a within-subjects design and the evidence levels were generally low. The overall results suggested that ankle foot orthosis-footwear combination tuning has the potential to improve the kinematics and kinetics of gait in children with cerebral palsy. However, the review highlights a lack of well-designed and adequately powered studies. Clinical relevance While the research described in this article indicates an improvement in the gait of children with cerebral palsy following tuning of their ankle foot orthosis-footwear combination, there is still a paucity of research with quantitative data on the effects of kinematics and kinetics of ankle foot orthosis-footwear combination tuning, comparing untuned ankle foot orthosis-footwear combinations with tuned ankle foot orthosis-footwear combination. Furthermore, current research does not identify the effect of tuning on energy efficiency.

Use of albendazole sulfoxide, albendazole sulfone, and combined solutions as scolicidal agents on hydatid cysts (in vitro study)

PubMed Central

Adas, Gokhan; Arikan, Soykan; Kemik, Ozgur; Oner, Ali; Sahip, Nilgun; Karatepe, Oguzhan

2009-01-01

AIM: To establish which scolicidal agents are superior and more suitable for regular use. METHODS: Echinococcus granulosus protoscoleces were obtained from 25 patients with liver hydatid cysts. Various concentrations of albendazole sulfone, albendazole sulfoxide, and albendazole sulfone and albendazole sulfoxide mixed together in concentrations of 50 μg/mL, and H2O2 in a concentration of 4%, NaCl 20%, and 1.5% cetrimide-0.15% chlorhexidine (10% Savlon-Turkey) were used to determine the scolicidal effects. Albendazole (ABZ) derivatives and other scolicidal agents were applied to a minimum of 100 scoleces for 5 and 10 min. The degree of viability was calculated according to the number of living scolices per field from a total of 100 scolices observed under the microscope. RESULTS: After 5 min, ABZ sulfone was 97.3% effective, ABZ sulfoxide was 98.4% effective, and the combined solution was 98.6% effective. When sulfone, sulfoxide and the combined solutions were compared, the combined solution seemed more effective than sulfone. However, there was no difference when the combined solution was compared with sulfoxide. After 10 min, hypertonic salt water, sulfone, sulfoxide, and the combined solution compared to other solutions looked more effective and this was statistically significant on an advanced level. When sulfone, sulfoxide, and the combined solutions were compared with each other, the combined solution appeared more effective than sulfone. When the combined solution was compared with sulfoxide, there was no difference. CONCLUSION: Despite being active, ABZ metabolites did not provide a marked advantage over 20% hypertonic saline. According to these results, we think creating a newly improved and more active preparation is necessary for hydatid cyst treatment. PMID:19115476

Are Chinese Correlative Conjunctions Psychologically Real? An Investigation of the Combination Frequency Effect.

PubMed

Kong, Lingyue; Zhang, John X; Zhang, Yongwei

2016-08-01

The present study used an online grammaticality judgment task to examine whether Chinese discontinuous correlative conjunctions are psychologically real in mental lexicon. High- and low-frequency discontinuous correlative conjunctions were compared with random combinations differing in combination frequencies but matched for constituent word frequency. Forty graduate students participated in the study. Results showed that responses were faster and more accurate for high-frequency correlative conjunctions than low-frequency ones, but the effects were absent for random combinations. The results indicate that Chinese discontinuous correlative conjunctions have psychological reality in mental lexicon in addition to the representation of their constituent words, and that grammatical functions of correlative conjunctions may be a critical factor for the formation of such holistic representations. © The Author(s) 2016.

On the displacement of leisure items by food during multiple-stimulus preference assessments.

PubMed Central

Bojak, S L; Carr, J E

1999-01-01

Previous studies have demonstrated that when food and leisure stimuli are combined in multiple-stimulus preference assessments, individuals typically select food more often, although the leisure stimuli also have known reinforcing properties. The purpose of the current study was to replicate this effect and determine its durability by examining the effect after mealtimes. Four adults who had been diagnosed with severe mental retardation were given three initial multiple-stimulus (without replacement) preference assessments (i.e., food, leisure stimuli, and combined). All participants selected food items as the most preferred stimuli in the combined assessments. Combined assessments were then administered immediately before and after the evening meal for each participant for 1 week. The results showed similar data both before and after mealtimes. PMID:10641304

Assessment of combined antiandrogenic effects of binary parabens mixtures in a yeast-based reporter assay.

PubMed

Ma, Dehua; Chen, Lujun; Zhu, Xiaobiao; Li, Feifei; Liu, Cong; Liu, Rui

2014-05-01

To date, toxicological studies of endocrine disrupting chemicals (EDCs) have typically focused on single chemical exposures and associated effects. However, exposure to EDCs mixtures in the environment is common. Antiandrogens represent a group of EDCs, which draw increasing attention due to their resultant demasculinization and sexual disruption of aquatic organisms. Although there are a number of in vivo and in vitro studies investigating the combined effects of antiandrogen mixtures, these studies are mainly on selected model compounds such as flutamide, procymidone, and vinclozolin. The aim of the present study is to investigate the combined antiandrogenic effects of parabens, which are widely used antiandrogens in industrial and domestic commodities. A yeast-based human androgen receptor (hAR) assay (YAS) was applied to assess the antiandrogenic activities of n-propylparaben (nPrP), iso-propylparaben (iPrP), methylparaben (MeP), and 4-n-pentylphenol (PeP), as well as the binary mixtures of nPrP with each of the other three antiandrogens. All of the four compounds could exhibit antiandrogenic activity via the hAR. A linear interaction model was applied to quantitatively analyze the interaction between nPrP and each of the other three antiandrogens. The isoboles method was modified to show the variation of combined effects as the concentrations of mixed antiandrogens were changed. Graphs were constructed to show isoeffective curves of three binary mixtures based on the fitted linear interaction model and to evaluate the interaction of the mixed antiandrogens (synergism or antagonism). The combined effect of equimolar combinations of the three mixtures was also considered with the nonlinear isoboles method. The main effect parameters and interaction effect parameters in the linear interaction models of the three mixtures were different from zero. The results showed that any two antiandrogens in their binary mixtures tended to exert equal antiandrogenic activity in the linear concentration ranges. The antiandrogenicity of the binary mixture and the concentration of nPrP were fitted to a sigmoidal model if the concentrations of the other antiandrogens (iPrP, MeP, and PeP) in the mixture were lower than the AR saturation concentrations. Some concave isoboles above the additivity line appeared in all the three mixtures. There were some synergistic effects of the binary mixture of nPrP and MeP at low concentrations in the linear concentration ranges. Interesting, when the antiandrogens concentrations approached the saturation, the interaction between chemicals were antagonistic for all the three mixtures tested. When the toxicity of the three mixtures was assessed using nonlinear isoboles, only antagonism was observed for equimolar combinations of nPrP and iPrP as the concentrations were increased from the no-observed-effect-concentration (NOEC) to effective concentration of 80%. In addition, the interactions were changed from synergistic to antagonistic as effective concentrations were increased in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP. The combined effects of three binary antiandrogens mixtures in the linear ranges were successfully evaluated by curve fitting and isoboles. The combined effects of specific binary mixtures varied depending on the concentrations of the chemicals in the mixtures. At low concentrations in the linear concentration ranges, there was synergistic interaction existing in the binary mixture of nPrP and MeP. The interaction tended to be antagonistic as the antiandrogens approached saturation concentrations in mixtures of nPrP with each of the other three antiandrogens. The synergistic interaction was also found in the equimolar combinations of nPrP and MeP, as well as nPrP and PeP, at low concentrations with another method of nonlinear isoboles. The mixture activities of binary antiandrogens had a tendency towards antagonism at high concentrations and synergism at low concentrations.

Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface.

PubMed

Belal, Mahmoud Helmy; Watanabe, Hisashi; Ichinose, Shizuko; Ishikawa, Isao

2012-07-01

Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed.

One-Health Simulation Modelling: Assessment of Control Strategies Against the Spread of Influenza between Swine and Human Populations Using NAADSM.

PubMed

Dorjee, S; Revie, C W; Poljak, Z; McNab, W B; McClure, J T; Sanchez, J

2016-04-01

Simulation models implemented using a range of parameters offer a useful approach to identifying effective disease intervention strategies. The objective of this study was to investigate the effects of key control strategies to mitigate the simultaneous spread of influenza among and between swine and human populations. We used the pandemic H1N1 2009 virus as a case study. The study population included swine herds (488 herds) and households-of-people (29,707 households) within a county in Ontario, Canada. Households were categorized as: (i) rural households with swine workers, (ii) rural households without swine workers and (iii) urban households without swine workers. Seventy-two scenarios were investigated based on a combination of the parameters of speed of detection and control strategies, such as quarantine strategy, effectiveness of movement restriction and ring vaccination strategy, all assessed at three levels of transmissibility of the virus at the swine-human interface. Results showed that the speed of detection of the infected units combined with the quarantine strategy had the largest impact on the duration and size of outbreaks. A combination of fast to moderate speed of the detection (where infected units were detected within 5-10 days since first infection) and quarantine of the detected units alone contained the outbreak within the swine population in most of the simulated outbreaks. Ring vaccination had no added beneficial effect. In conclusion, our study suggests that the early detection (and therefore effective surveillance) and effective quarantine had the largest impact in the control of the influenza spread, consistent with earlier studies. To our knowledge, no study had previously assessed the impact of the combination of different intervention strategies involving the simultaneous spread of influenza between swine and human populations. © 2014 Blackwell Verlag GmbH.

Direct and protective effects of single or combined addition of vincristine and ε-viniferin on human HepG2 cellular oxidative stress markers in vitro.

PubMed

Tarhan, Seda; Özdemir, Filiz; İncesu, Zerrin; Demirkan, Emine Sütken

2016-08-01

The objective of this study is to examine the direct effects of low doses and high doses of ε-viniferin, a substance known to be an antioxidant, and vincristine sulphate, a chemotherapeutic agent, alone and in combination [ε-viniferin + vincristine] on HepG2 cell strain, as well as evaluate oxidative stress after incubation periods of 3, 6, and 24 h. Direct effect was determined right after the incubation period; however, for protective effect, antioxidant protection response was determined after the treatment for 1 h with 500 μM H2O2, which is an oxidative stressor. For this purpose, superoxide dismutase was determined for enzyme activity, and lipid hydroperoxide (LPO) and reduced glutathione concentrations were studied as indicators of oxidative stress. Results show that low [3.63 µM vincristine + 3.75 µM ε-viniferin] and high [11.25 µM vincristine + 15.8 µM ε-viniferin] doses of combination groups showed similar direct antioxidant effect on LPO levels as protective when compared to the H2O2 control group (p < 0.05). Superoxide dismutase enzyme showed a direct antioxidant effect in low and high dose combination groups. In addition, when the incubation period was increased to 24 h, a protective effect was observed in both dose groups (p < 0.05). Reduced glutathione activities showed a direct effect in the low dose combination group, and a protective effect in both the low and high doses in the 24 h. These results show that combined usage of drugs in HepG2 cell strain possesses a protective effect against exogenically produced oxidative stress conditions.

The combined toxicological effects of titanium dioxide nanoparticles and bisphenol A on zebrafish embryos

PubMed Central

2014-01-01

Environmental pollutants co-exist and exhibit interaction effects that are different from those associated with a single pollutant. As one of the more commonly manufactured nanomaterials, titanium dioxide nanoparticles (TiO2-NPs) are most likely to bind to other contaminants in water. In this paper, we aimed to study the combined toxicological effects of TiO2-NPs and bisphenol A (BPA) on organism. First, in vitro adsorption experiments were conducted to determine the adsorptive interaction between TiO2-NPs and BPA. Second, zebrafish embryo toxicity tests were performed to monitor for changes in the toxicological effects associated with the two chemicals. The study results demonstrated that adsorptive interactions exist between the two chemicals and increased toxicity effects which included an advanced toxicological effect time, decreased survival, increased morphological abnormalities, and delayed embryo hatching. Also, we suggest that the mode of combined action has a synergistic effect. Based on this, we postulate that concomitant exposure to TiO2-NPs and BPA increased BPA bioavailability and uptake into cells and organisms. Further studies are required to understand the mechanisms of interactions of this mixture. PMID:25177222

Interactive effects of N-acetylcysteine and antidepressants.

PubMed

Costa-Campos, Luciane; Herrmann, Ana P; Pilz, Luísa K; Michels, Marcus; Noetzold, Guilherme; Elisabetsky, Elaine

2013-07-01

N-acetylcysteine (NAC), a glutathione precursor and glutamate modulator, has been shown to possess various clinically relevant psychopharmacological properties. Considering the role of glutamate and oxidative stress in depressive states, the poor effectiveness of antidepressant drugs (ADs) and the benefits of drug combination for treating depression, the aim of this study was to explore the possible benefit of NAC as an add on drug to treat major depression. For that matter we investigated the combination of subeffective and effective doses of NAC with subeffective and effective doses of several ADs in the mice tail suspension test. The key finding of this study is that a subeffective dose of NAC reduced the minimum effective doses of imipramine and escitalopram, but not those of desipramine and bupropion. Moreover, the same subeffective dose of NAC increased the minimum effective dose of fluoxetine in the same model. In view of the advantages associated with using the lowest effective dose of antidepressant, the results of this study suggest the potential of a clinically useful interaction of NAC with imipramine and escitalopram. Further studies are necessary to better characterize the molecular basis of such interactions, as well as to typify the particular drug combinations that would optimize NAC as an alternative for treating depression. Copyright © 2013 Elsevier Inc. All rights reserved.

Single vs. combination immunotherapeutic strategies for glioma

PubMed Central

Chandran, Mayuri; Candolfi, Marianela; Shah, Diana; Mineharu, Yohei; Yadav, Vivek; Koschmann, Carl; Asad, Antonela S.; Lowenstein, Pedro R.; Castro, Maria G.

2017-01-01

Introduction Malignant gliomas are highly invasive tumors, associated with a dismal survival rate despite standard of care, which includes surgical resection, radiotherapy and chemotherapy with temozolomide (TMZ). Precision immunotherapies or combinations of immunotherapies that target unique tumor-specific featuresmay substantially improve upon existing treatments. Areas covered Clinical trials of single immunotherapies have shown therapeutic potential in high-grade glioma patients, and emerging preclinical studies indicate that combinations of immunotherapies may be more effective than monotherapies. In this review we discuss emerging combinations of immunotherapies and compare efficacy of single vs. combined therapies tested in preclinical brain tumor models. Expert opinion Malignant gliomas are characterized by a number of factors which may limit the success of single immunotherapies including inter-tumor and intra-tumor heterogeneity, intrinsic resistance to traditional therapies, immunosuppression, and immune selection for tumor cells with low antigenicity. Combination of therapies which target multiple aspects of tumor physiology are likely to be more effective than single therapies. While we describe a limited number of combination immunotherapies which are currently being tested in preclinical and clinical studies, the field is expanding at an astounding rate, and endless combinations remain open for exploration. PMID:28286975

Combined effect of three insect growth regulators on the digestive enzymatic profiles of Callosobruchus maculatus (Coleoptera: Bruchidae).

PubMed

Khatter, Najat Aly; Abuldahb, Faten Farid

2011-12-01

Insect growth regulators (IGRs) are insecticides that mimic insect produced hormones by regulatingdevelopmental process. Theyhave little or no mammalian toxicity, and are considered reduced-risk insecticides that are often exempt from tolerance requirements of regulatory agencies. IGRs, especially, chlorfluazuron, hydroprene and hexaflumuron (benzoylphenylurea) are currently studied because of possibility of using in stored products protection. Many of IGRs compounds usedin insect pests control are known to affect digestive enzymes. Chlorfluazuron, hydroprene and hexaflumuronwere tested topically at doses of 0.25%, 0.5%&1% for chlorfluazuron and hydroprene and 0.5, 1 & 2 microg/ml of hexaflumuron to investigate its effects on the activities of the digestive enzymes protease, amylase and lipase in Callosobruchusmaculatus larvae, which were affected by IGRs individually and in combination. When combined, the effect was more sever at low concentration. There were statistically significant differences (P < or = 0.05) in enzyme activities in combined and individual treatments. Combination three IGRs caused a two-fold decrease in enzyme activity even at reduced concentration. Clear dose-response relationships were established with respect to enzyme activity. A synergistic effect of IGRs was found by combination of low doses. These effects are most pronounced in early instars.

Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours.

PubMed

Pereira, Melanie C; Mohammed, Raushaan; VAN Otterlo, Willem A L; DE Koning, Charles B; Davids, Hajierah

2017-12-01

Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. Rau 015 (15 μM) and curcumin (112.5 μM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 μM) and curcumin (100 μM) displayed similar effects in MCF-7 and MG-63 cells. We report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when combined with curcumin. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells.

PubMed

Delwar, Zahid M; Avramidis, Dimitrios; Follin, Elna; Hua, Yan; Siden, Åke; Cruz, Mabel; Paulsson, Kajsa M; Yakisich, Juan Sebastian

2012-08-01

Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.05MG human glioma cells. A stronger antiproliferative effect was observed in the short-term proliferation assay with the M:SO combination compared to either investigated agent alone. In the long-term proliferation assay, a 10-day exposure to M:SO at concentrations of 10 μM:17.5 μM or 17.5 μM:10 μM was enough to kill 100% of the cells; no cell regrowth was observed after re-incubation in drug-free media. When used in combination, the single concentration of M and SO could be decreased by 2.5- to 5-fold of those used for each experimental drug alone and still obtain a similar antiproliferative effect. The underlying molecular mechanism was investigated by co-incubating M:SO with dithiothreitol (DTT) and genistein. Both substances partially neutralized the effects of the M:SO combination, showing additive effects. This observation suggests a role of oxidative stress and tyrosine kinase stimulation in the M:SO cytotoxic effect. Our results indicate that M:SO combination is an attractive alternative for glioma treatment that encourages further study. The neutralizing effects of genistein and DTT reveal a possibility for their use in the minimization of potential M:SO systemic toxicity.

Reduced hemostatic effects with drospirenone-based oral contraceptives containing estetrol vs. ethinyl estradiol.

PubMed

Kluft, Cornelis; Zimmerman, Yvette; Mawet, Marie; Klipping, Christine; Duijkers, Ingrid J M; Neuteboom, Jacoline; Foidart, Jean-Michel; Bennink, Herjan Coelingh

2017-02-01

The effects of estetrol (E4), a natural fetal estrogen, combined with drospirenone (DRSP) were evaluated on plasma levels of sex hormone-binding globulin (SHBG), angiotensinogen and 12 hemostasis markers. Combinations of 3 mg DRSP with 5 or 10 mg E4 were compared with YAZ® (20 mcg ethinyl estradiol and 3 mg DRSP; EE/DRSP) in parallel groups of 15-18 healthy young women. Main outcome was the relative change from pretreatment to the end (day 24±1) of the third treatment cycle. All E4 combinations showed low estrogen impact compared to EE/DRSP. Effects on SHBG and angiotensinogen of 10 mg E4 combined with DRSP were 15%-20% that of EE/DRSP. Both E4/DRSP combinations reduced D-dimer level and the 5 mg E4/DRSP combination also decreased fragment 1+2. The reduction in coagulation markers suggests an anticoagulant effect from DRSP. The indications of a low thrombosis risk for E4 preparations should be validated in larger studies. IMPLICATION STATEMENT. Copyright © 2016 Elsevier Inc. All rights reserved.

Quercetin and rutin as potential agents antifungal against Cryptococcus spp.

PubMed

Oliveira, V M; Carraro, E; Auler, M E; Khalil, N M

2016-01-01

Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting as cryptococcosis the immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with quercetin or rutin and as a protective of citotoxic effect. The antifungal activity to amphotericin B, quercetin and rutin alone and in combination was determined in Candida sp and Cryptococcus neoformans strains. Cytotoxicity test on erythrocytes was performed by spectrophotometric absorbance of hemoglobin. The amphotericin B MIC was reduced when used in combination with quercetin or rutin to C. neoformans ATCC strain and reduced when combined with rutin to a clinical isolate of C. neoformans. In addition, the combination of quercetin with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that quercetin and rutin are potential agents to combine with amphotericin B in order to reduce the amphotericin dose to lessen side effects and improve antifungal efficacy.

Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

PubMed

Burda-Malarz, Kinga; Kus, Krzysztof; Ratajczak, Piotr; Czubak, Anna; Hardyk, Szymon; Nowakowska, Elżbieta

2014-07-01

Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt's forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

Combined effects of simulated acid rain and lanthanum chloride on chloroplast structure and functional elements in rice.

PubMed

Hu, Huiqing; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2016-05-01

Acid rain and rare earth element (REE) pollution exist simultaneously in many agricultural regions. However, how REE pollution and acid rain affect plant growth in combination remains largely unknown. In this study, the combined effects of simulated acid rain and lanthanum chloride (LaCl3) on chloroplast morphology, chloroplast ultrastructure, functional element contents, chlorophyll content, and the net photosynthetic rate (P n) in rice (Oryza sativa) were investigated by simulating acid rain and rare earth pollution. Under the combined treatment of simulated acid rain at pH 4.5 and 0.08 mM LaCl3, the chloroplast membrane was smooth, proteins on this membrane were uniform, chloroplast structure was integrated, and the thylakoids were orderly arranged, and simulated acid rain and LaCl3 exhibited a mild antagonistic effect; the Mg, Ca, Mn contents, the chlorophyll content, and the P n increased under this combined treatment, with a synergistic effect of simulated acid rain and LaCl3. Under other combined treatments of simulated acid rain and LaCl3, the chloroplast membrane surface was uneven, a clear "hole" was observed on the surface of chloroplasts, and the thylakoids were dissolved and loose; and the P n and contents of functional elements (P, Mg, K, Ca, Mn, Fe, Ni, Cu, Zn and Mo) and chlorophyll decreased. Under these combined treatments, simulated acid rain and LaCl3 exhibited a synergistic effect. Based on the above results, a model of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis was established in order to reveal the combined effects on plant photosynthesis, especially on the photosynthetic organelle-chloroplast. Our results would provide some references for further understanding the mechanism of the combined effects of simulated acid rain and LaCl3 on plant photosynthesis.

Economic Evaluation of a School-based Combined Program with a Targeted Pit and Fissure Sealant and Fluoride Mouth Rinse in Japan.

PubMed

Sakuma, Shihoko; Yoshihara, Akihiro; Miyazaki, Hideo; Kobayashi, Seigo

2010-01-01

In Niigata prefecture, Japan, a system has been developed based on a school-based fluoride mouth rinse program as follows; students with caries susceptible teeth are screened in a school dental examination, and encouraged to receive sealant placement in local dental clinics. However, the cost-effectiveness of sealant application in the public health has been questioned. The aim of this study was to estimate of the cost-effectiveness and cost-benefit ratio for a school-based combined program with fluoride mouth rinse and targeted fissure sealant in children residing in non-fluoridated areas in Japan. The analysis was based on comparing an intervention group with two cohorts in the 8-year-old (n=66) and 11-year-old (n=58) participating in the combined program for four and seven years, respectively, with a control group of the same grades (n=43 and n=54 respectively). The study measured mean differences in number of decayed and filled teeth (DFT) between the study groups and a combined program cost per child during study periods. The cost-effectiveness ratio was expressed as an individual annual program cost per DFT averted. In the cost-benefit ratio the mean difference in treatment cost between groups (program benefit) was compared to program cost. The mean reduced DFT differences between groups were 1.44 in 8-year-old and 3.17 in 11-year-old children. The cost-effectiveness ratio was ¥ 493 in the 8-year-old and ¥ 202 in the 11-year-old, respectively. The cost-benefit ratio was 1.84 in 8-year-old children and 2.42 in 11-year-old. This combined program indicated acceptable cost-effectiveness and cost -benefit ratio.

Age influences the effects of nicotine and monoamine oxidase inhibition on mood-related behaviors in rats.

PubMed

Villégier, Anne-Sophie; Gallager, Brittney; Heston, Jon; Belluzzi, James D; Leslie, Frances M

2010-03-01

Epidemiological studies have demonstrated a comorbidity of smoking with depression and anxiety, particularly during adolescence. However, few animal studies have considered possible synergistic interactions between nicotine and other tobacco smoke constituents, such as monoamine oxidase (MAO) inhibitors, in the regulation of mood. The aim of the study was to test the hypothesis that nicotine combined with the irreversible MAO inhibitor, tranylcypromine, will differentially affect depression- and anxiety-related behaviors in adolescent and adult rats. Nicotine (0, 0.05, 0.2 mg/kg, s.c.) and tranylcypromine (3 mg/kg, i.p.) were tested separately, or together, on male rats aged postnatal days 30 and 68, in three mood-related behavioral tests: forced swim test (FST), elevated plus maze (EPM), and open field. Nicotine (0.2 mg/kg) in adults significantly decreased floating time in the FST and increased time spent in the open arm of the EPM, with no change in locomotor activity. Tranylcypromine pretreatment combined with nicotine (0.2 mg/kg) significantly increased locomotor activity and time spent in the center of the open field. Whereas nicotine alone had no significant effect on adolescents, it significantly increased locomotor activity and decreased floating time in the FST when combined with tranylcypromine pretreatment. There is an age-dependent effect of nicotine, alone and in combination with MAO inhibition, on mood-related behaviors. Whereas nicotine alone induces mood improvement in adults, it has no effect on adolescents. Nicotine combined with tranylcypromine has unique, age-dependent effects. Thus, experimental studies of smoking should consider both age and other tobacco constituents, such as MAO inhibitors, as critical factors.

[Chaperon-like anticataract agents, the antiaggregants of lens crystallin. Communication 4. Study of the effect of a mixture of di- and tetrapeptides on a prolonged rat model of UV-induced cataract].

PubMed

Avetisov, S E; Polunin, G S; Sheremet, N L; Makarov, I A; Fedorov, A A; Karpova, O E; Muranov, K O; Dizhevskaia, A K; Soustov, L V; Chelnokov, E V; Bitiurin, N M; Sapogova, N V; Nemov, V V; Bodyrev, A A; Ostrovskiĭ, M A

2008-01-01

There is a potential of therapeutic action on certain stages of caractogenesis, in particular on the aggregation of water-soluble proteins of cytoplasmic lens fiber cells, giving rise to insoluble protein complexes. The effect of a combined preparation (N-acetyl carnosine and D-patethine), acting by the chaperon-like mechanism, was studied in vivo on a prolonged rat model of UV-induced cataract. The use of the combined preparation consisting of a mixture of peptides of N-acetyl carnosine and D-patethine in a ratio of 1:1 as ocular instillations and intraperitoneal injections could slow down the development of UV-induced cataract in vivo. Pathomorphological studies suggest that the combined preparation has a protective effect on lens tissue when the rat model of UV-induced cataract is employed.

Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review of its use in the management of asthma.

PubMed

Markham, A; Adkins, J C

2000-12-01

Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone propionate alone. The combination product also appears to improve HR-QOL relative to placebo or salmeterol alone.

The Effects of Parent Participation on Child Psychotherapy Outcome: A Meta-Analytic Review

ERIC Educational Resources Information Center

Dowell, Kathy A.; Ogles, Benjamin M.

2010-01-01

Forty-eight child psychotherapy outcome studies offering direct comparisons of an individual child treatment group to a combined parent-child/family therapy treatment group were included in this meta-analytic review. Results indicate that combined treatments produced a moderate effect beyond the outcomes achieved by individual child treatments,…

The Misdirection of Public Policy: Comparing and Combining Standardised Effect Sizes

ERIC Educational Resources Information Center

Simpson, Adrian

2017-01-01

Increased attention on "what works" in education has led to an emphasis on developing policy from evidence based on comparing and combining a particular statistical summary of intervention studies: the standardised effect size. It is assumed that this statistical summary provides an estimate of the educational impact of interventions and…

Neuroprotective Effect of Antioxidants and Moderate Hypoxia as Combined Preconditioning in Cerebral Ischemia.

PubMed

Levchenkova, O S; Novikov, V E; Parfenov, E A; Kulagin, K N

2016-12-01

We studied combined effect of moderate hypoxia and compounds pQ-4, pQ-915, pQ-1032, and pQ-1104 on neurological deficit and survival of rats after bilateral ligation of common carotid arteries. Preconditioning including moderate hypoxia and treatment with compound pQ-4 produced a neuroprotective effect and increased animal survival during the early (by 51%) and late (by 33.5%) periods of modeled ischemia and reduced neurological deficit (by 50% and 41%, respectively). Moreover, this combination of preconditioning factors prevented postischemic excessive activation of free radical oxidation in brain hemispheres and blood serum.

In vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts against Haemonchus contortus (Nematoda) and their anthelmintic effect in gerbils.

PubMed

Zamilpa, A; García-Alanís, C; López-Arellano, M E; Hernández-Velázquez, V M; Valladares-Cisneros, M G; Salinas-Sánchez, D O; Mendoza-de Gives, P

2018-05-06

The in vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts (E-Cham and E-Cato, respectively) on Haemonchus contortus infective larvae (L3) and the anthelmintic effect of these extracts against the pre-adult stage of the parasite in gerbils were evaluated using both individual and combined extracts. The in vitro confrontation between larvae and extracts was performed in 24-well micro-titration plates. The results were considered 24 and 72 h post confrontation. The in vivo nematicidal effect was examined using gerbils as a study model. The extracts from the two assessed plants were obtained through maceration using n-hexane as an organic agent. Gerbils artificially infected with H. contortus L3 were treated intraperitoneally with the corresponding extract either individually or in combination. The results showed that the highest individual lethal in vitro effect (96.3%) was obtained with the E-Cham extract at 72 h post confrontation at 40 mg/ml, followed by E-Cato (78.9%) at 20 mg/ml after 72 h. The highest combined effect (98.7%) was obtained after 72 h at 40 mg/ml. The in vivo assay showed that the individual administration of the E-Cato and E-Cham extracts reduced the parasitic burden in gerbils by 27.1% and 45.8%, respectively. Furthermore, the anthelmintic efficacy increased to 57.3% when both extracts were administered in combination. The results of the present study show an important combined nematicidal effect of the two plant extracts assessed against L3 in gerbils.

Immunomodulatory/inflammatory effects of geopropolis produced by Melipona fasciculata Smith in combination with doxorubicin on THP-1 cells.

PubMed

Oliveira, Lucas Pires Garcia; Conte, Fernanda Lopes; Cardoso, Eliza de Oliveira; Conti, Bruno José; Santiago, Karina Basso; Golim, Marjorie de Assis; Cruz, Maria Teresa; Sforcin, José Maurício

2016-12-01

Geopropolis (GEO) in combination with doxorubicin (DOX) reduced HEp-2 cells viability compared to GEO and DOX alone. A possible effect of this combination on the innate immunity could take place, and its effects were analysed on THP-1 cell - a human leukaemia monocytic cell line used as a model to study monocyte activity and macrophage activity, assessing cell viability, expression of cell markers and cytokine production. THP-1 cells were incubated with GEO, DOX and their combination. Cell viability was assessed by MTT assay, cell markers expression by flow cytometry and cytokine production by ELISA. GEO + DOX did not affect cell viability. GEO alone or in combination increased TLR-4 and CD80 but not HLA-DR and TLR-2 expression. GEO stimulated TNF-α production while DOX alone or in combination did not affect it. GEO alone or in combination inhibited IL-6 production. GEO exerted a pro-inflammatory profile by increasing TLR-4 and CD80 expression and TNF-α production, favouring the activation of the immune/inflammatory response. GEO + DOX did not affect cell viability and presented an immunomodulatory action. Lower concentrations of DOX combined to GEO could be used in cancer patients, avoiding side effects and benefiting from the biological properties of GEO. © 2016 Royal Pharmaceutical Society.

Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults.

PubMed

Li, Bing; Zhu, Xinyi; Hou, Jianhua; Chen, Tingji; Wang, Pengyun; Li, Juan

2016-01-01

As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. www.chictr.org.cn, identifier ChiCTR-OON-16007793.

An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac

PubMed Central

Woode, Eric; Ameyaw, Elvis Ofori; Abotsi, Wonder Kofi Mensah; Boakye-Gyasi, Eric

2015-01-01

Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac. PMID:26692735

Effects of Problem-Based Learning on Attitude: A Meta-Analysis Study

ERIC Educational Resources Information Center

Demirel, Melek; Dagyar, Miray

2016-01-01

To date, researchers have frequently investigated students' attitudes toward courses supported by problem-based learning. There are several studies with different results in the literature. It is necessary to combine and interpret the findings of these studies through a meta-analysis method. This method aims to combine different results of similar…

Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis.

PubMed

Karssemeijer, Esther G A; Aaronson, Justine A; Bossers, Willem J; Smits, Tara; Olde Rikkert, Marcel G M; Kessels, Roy P C

2017-11-01

Combined cognitive and physical exercise interventions have potential to elicit cognitive benefits in older adults with mild cognitive impairment (MCI) or dementia. This meta-analysis aims to quantify the overall effect of these interventions on global cognitive functioning in older adults with MCI or dementia. Ten randomized controlled trials that applied a combined cognitive-physical intervention with cognitive function as an outcome measure were included. For each study effect sizes were computed (i.e., post-intervention standardized mean difference (SMD) scores) and pooled, using a random-effects meta-analysis. The primary analysis showed a small-to-medium positive effect of combined cognitive-physical interventions on global cognitive function in older adults with MCI or dementia (SMD[95% confidence interval]=0.32[0.17;0.47], p<0.00). A combined intervention was equally beneficial in patients with dementia (SMD=0.36[0.12;0.60], p<0.00) and MCI (SMD=0.39[0.15;0.63], p<0.05). In addition, the analysis showed a moderate-to-large positive effect after combined cognitive-physical interventions for activities of daily living (ADL) (SMD=0.65[0.09;1.21], p<0.01)and a small-to-medium positive effect for mood (SMD=0.27[0.04;0.50], p<0.01). These functional benefits emphasize the clinical relevance of combined cognitive and physical training strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy of Cimicifuga racemosa, Hypericum perforatum and Agnus castus in the treatment of climacteric complaints: a systematic review.

PubMed

Laakmann, Elena; Grajecki, Donata; Doege, Katja; zu Eulenburg, Christine; Buhling, Kai J

2012-09-01

The systematic review examines whether Cimicifuga racemosa (CR), Hypericum perforatum (HP), Agnus castus, vitamins and minerals, either as monotherapy or in combination, have an evidence-based impact on vasomotor, genital and psychological climacteric complaints. DATA SOURCES AND METHODS OF STUDY SELECTION: We searched in the databases EMBASE, OVID and PubMed using the keywords "vasomotor symptoms, hot flashes, vaginal atrophy, psychological problems, endometrium, sleep, concentration, cognition in combination with vitamins, multivitamins, minerals, multiminerals, black cohosh, Cimicifuga, Agnus castus, chasteberry, chaste tree, monk's pepper and menopause" for randomized controlled trials (RCT). Relevant studies were reviewed by four independent reviewers qualitatively. Most of the studies with a comparison of CR vs. placebo do not show an evidence-based significant effect of CR on climacteric symptoms. The combination of CR and HP shows an improvement of climacteric complaints in comparison to placebo. In some RCTs, there was no significant difference between CR and hormone-replacement therapy. The combination of HP and Agnus castus showed no significant difference in the treatment of climacteric complaints. CR monotherapy as well as HP and Agnus castus showed no better effect than placebo. The combination of CR with HP demonstrated a positive effect on climacteric complaints.

Effect of lipoic acid combined with paclitaxel on breast cancer cells.

PubMed

Li, B J; Hao, X Y; Ren, G H; Gong, Y

2015-12-22

Breast cancer is the most common gynecologic tumor globally that threatens women's health. Lipoic acid is a type of antioxidant that can alleviate oxidative stress damage. Studies showed that lipoic acid could inhibit the proliferation of tumor cells in cervical cancer and colon cancer. This paper intends to explore the combined effect of lipoic acid and paclitaxel on breast cancer cells. Breast cancer MCF-7 cells were divided into four groups: control group, lipoic acid group, paclitaxel group, and a combination group. MTT was applied to detect the drugs' influence on breast cancer cell proliferation. A colony formation test was used to determine the effects on breast cancer cell clone formation rate. Western blot was performed to detect the effects on nuclear factor (NF)-κB. Lipoic acid alone can inhibit tumor cell proliferation and clone formation with time dependence. Compared with the control, paclitaxel alone can significantly suppress tumor cell proliferation and clone formation (P < 0.05). Lipoic acid and paclitaxel in combination obviously strengthened their individual inhibitory effects on tumor cells (P < 0.05). Compared with the paclitaxel alone group, the combination group exhibited more remarkable inhibitory effect (P < 0.05). Lipoic acid alone or combined with paclitaxel can inhibit NF-κB expression and inhibit breast cancer cell proliferation.

Combination inhaled steroid and long-acting beta₂-agonist in addition to tiotropium versus tiotropium or combination alone for chronic obstructive pulmonary disease.

PubMed

Rojas-Reyes, Maria Ximena; García Morales, Olga M; Dennis, Rodolfo J; Karner, Charlotta

2016-06-06

The long-acting bronchodilator tiotropium and single-inhaler combination therapy of inhaled corticosteroids and long-acting beta2-agonists (ICS/LABA) are commonly used for maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Combining these treatments, which have different mechanisms of action, may be more effective than administering the individual components. To assess relative effects of the following treatments on markers of exacerbations, symptoms, quality of life and lung function in patients with COPD.• Tiotropium plus LABA/ICS versus tiotropium.• Tiotropium plus LABA/ICS versus LABA/ICS. We searched the Cochrane Airways Group Specialised Register of Trials (April 2015), ClinicalTrials.gov (www.ClinicalTrials.gov), the World Health Organization (WHO) trials portal and reference lists of relevant articles. We included parallel, randomised controlled trials (RCTs) lasting three months or longer conducted to compare ICS and LABA combination therapy in addition to inhaled tiotropium versus tiotropium alone or combination therapy alone. We independently assessed trials for inclusion, then extracted data on trial quality and outcome results. We contacted study authors to ask for additional information. We collected trial information on adverse effects. Tiotropium plus LABA/ICS versus tiotropiumWe included six studies (1902 participants) with low risk of bias that compared tiotropium in addition to inhaled corticosteroid and long-acting beta2-agonist combination therapy versus tiotropium alone. Investigators found no statistically significant differences in mortality between treatments (odds ratio (OR) 1.80, 95% confidence interval (CI) 0.55 to 5.91; two studies; 961 participants), a reduction in all-cause hospitalisations with the use of combined therapy (tiotropium + LABA/ICS) (OR 0.61, 95% CI 0.40 to 0.92; two studies; 961 participants; number needed to treat for an additional beneficial outcome (NNTB) 19.7, 95% CI 10.75 to 123.41). The effect on exacerbations was heterogeneous among trials and was not meta-analysed. Health-related quality of life measured by St. George's Respiratory Questionnaire (SGRQ) showed a statistically significant improvement in total scores with use of tiotropium + LABA/ICS compared with tiotropium alone (mean difference (MD) -3.46, 95% CI -5.05 to -1.87; four studies; 1446 participants). Lung function was significantly different in the combined therapy (tiotropium + LABA/ICS) group, although average benefit with this therapy was small. None of the included studies included exercise tolerance as an outcome.A pooled estimate of these studies did not show a statistically significant difference in adverse events (OR 1.16, 95% CI 0.92 to 1.47; four studies; 1363 participants), serious adverse events (OR 0.86, 95% CI 0.57 to 1.30; four studies; 1758 participants) and pneumonia (Peto OR 1.62, 95% CI 0.54 to 4.82; four studies; 1758 participants). Tiotropium plus LABA/ICS versus LABA/ICSOne of the six studies (60 participants) also compared combined therapy (tiotropium + LABA/ICS) versus LABA/ICS therapy alone. This study was affected by lack of power; therefore results did not allow us to draw conclusions for this comparison. In this update, we found new moderate-quality evidence that combined tiotropium + LABA/ICS therapy compared with tiotropium plus placebo decreases hospital admission. Low-quality evidence suggests an improvement in disease-specific quality of life with combined therapy. However, evidence is insufficient to support the benefit of tiotropium + LABA/ICS for mortality and exacerbations (moderate- and low-quality evidence, respectively). Of note, not all participants enrolled in the included studies would be candidates for triple therapy according to current international guidance.Compared with the use of tiotropium plus placebo, tiotropium + LABA/ICS-based therapy does not increase undesirable effects such as adverse events or serious non-fatal adverse events.

Single and combined effects of microcystin- and saxitoxin-producing cyanobacteria on the fitness and antioxidant defenses of cladocerans.

PubMed

da S Ferrão-Filho, Aloysio; de Abreu S Silva, Daniel; de Oliveira, Taissa A; de Magalhães, Valéria Freitas; Pflugmacher, Stephan; da Silva, Eduardo Mendes

2017-10-01

Cyanobacteria produce different toxic compounds that affect animal life, among them hepatotoxins and neurotoxins. Because cyanobacteria are able to produce a variety of toxic compounds at the same time, organisms may be, generally, subjected to their combined action. In the present study, we demonstrate the single and combined effects on cladocerans of cyanobacteria that produce microcystins (hepatotoxins) and saxitoxins (neurotoxins). Animals were exposed (either singly or combined) to 2 strains of cyanobacteria isolated from the same environment (Funil Reservoir, Rio de Janeiro, Brazil). The effects on clearance rate, mobility, survivorship, fecundity, population increase rate (r), and the antioxidant enzymes glutathione-S-transferase (GST) and catalase (CAT) were measured. Cladoceran species showed a variety of responses to cyanobacterial exposures, going from no effect to impairment of swimming movement, lower survivorship, fecundity, and general fitness (r). Animals ingested cyanobacteria in all treatments, although at lower rates than good food (green algae). Antioxidant defense responses were in accordance with fitness responses, suggesting that oxidative stress may be related to such effects. The present study emphasizes the need for testing combined actions of different classes of toxins, because this is often, and most likely, the scenario in a more eutrophic world with global climatic changes. Environ Toxicol Chem 2017;36:2689-2697. © 2017 SETAC. © 2017 SETAC.

[Study on active constituents of traditional Chinese medicine reversing multidrug resistance of tumor cells in vitro].

PubMed

Zhang, H; Yang, L; Liu, S; Ren, L

2001-09-01

To screen drugs reversing multidrug resistance of tumor cells from active constituents of traditional Chinese medicine and to study the reversal action. The kill effects of the drugs on tumor cell lines in vitro were determined with MTT method. The Jin's formula was used to analyse the effect of drug combination. 5 micrograms/ml rhynchophylline, 2 micrograms/ml jatrorrhizine and 1.25 micrograms/ml indirulin could reverse multidrug resistance for vincristine on KBv200 cell line by 16.8, 5.1 and 4 fold respectively. 1.56-12.5 micrograms/ml curcumine combining with vincristine could sensitize antitumor effect both on KB and KBv200 cell lines. All rhynchophylline, jatrorrhizine and indirulin could reverse multidrug resistance for vincristine on KBv200 cell line. Curcumine combinating vincristine could sensitize antitumor effect both on kB and kBv200 cell lines.

Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis.

PubMed

Azuine, M A; Bhide, S V

1992-05-28

The inhibitory effect of oral administration of betel-leaf extract (BLE) and 2 of its constituents, beta-carotene and alpha-tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN-OAC)-induced oral carcinogenesis in Syrian hamsters was studied. DMN-OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent site-specific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer.

Analysis of the combined effects of lanthanum and acid rain, and their mechanisms, on nitrate reductase transcription in plants.

PubMed

Xia, Binxin; Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua

2017-04-01

Rare earth element (REE) pollution and acid rain are major global environmental concerns, and their spatial distributions overlap. Thus, both forms of pollution combine to act on plants. Nitrogen is important for plant growth, and nitrate reductase (NR) is a key plant enzyme that catalyzes nitrogen assimilation. Studying the combined effects of REEs and acid rain on plant nitrogen-based nutrients has important environmental significance. Here, soybean (Glycine max) plants, commonly used for toxicological studies, were exposed to lanthanum (La), a REE, and acid rain to study the NR activities and NR transcriptional levels in the roots. To explain how the pollution affected the NR transcriptional level, we simultaneously observed the contents of intracellular La and nutrient elements, protoplast morphology, membrane lipid peroxidation and intracellular pH. A combined treatment of 0.08mmol/L La and pH 4.5 acid rain increased the NR activity, decreased the NR transcriptional level, increased the intracellular nutrient elements' contents and caused deformations in membrane structures. Other combined treatments significantly decreased the aforementioned parameters and caused serious damage to the membrane structures. The variation in the amplitudes of combined treatments was greater than those of individual treatments. Compared with the control and individual treatments, combined treatments increased membrane permeability, the malondialdehyde content, and intracellular H + and La contents, and with an increasing La concentration or acid strength, the change in amplitude increased. Thus, the combined effects on NR gene transcription in soybean seedling roots were related to the intracellular nutrient elements' contents, protoplast morphology, membranous lipid peroxidation, intracellular pH and La content. Copyright © 2016 Elsevier Inc. All rights reserved.

Protective effects of edaravone combined puerarin on inhalation lung injury induced by black gunpowder smog.

PubMed

Wang, Zhengguan; Li, Ruibing; Liu, Yifan; Liu, Xiaoting; Chen, Wenyan; Xu, Shumin; Guo, Yuni; Duan, Jinyang; Chen, Yihong; Wang, Chengbin

2015-05-01

The present study aimed to investigate the combined effects of puerarin with edaravone on inhalation lung injury induced by black gunpowder smog. Male Wistar rats were divided into five groups (control group, edaravone group, puerarin group, edaravone combined with puerarin group and inhalation group). The severity of pulmonary injuries was evaluated after inducing acute lung injury. Arterial blood gas, inflammatory cytokines, biochemical, parameters, cell counting, W/D weight ratio and histopathology were analyzed. Results in lung tissues, either edaravone or puerarin treatment alone showed significant protective effects against neutrophil infiltration and tissue injury, as demonstrated by myeloperoxidase activity and histopathological analysis (all p<0.05). In addition, combined treatment with both edaravone and puerarin demonstrated additive protective effects on smog-induced lung injury, compared with single treatment. Combination of edaravone and puerarin shows promise as a new treatment option for acute lung injury/acute respiratory distress syndrome patients. Copyright © 2015 Elsevier B.V. All rights reserved.

In Vitro Anti-Candida Activity of Lidocaine and Nitroglycerin: Alone and Combined

PubMed Central

Palmeira-de-Oliveira, Ana; Ramos, Ana Rita; Gaspar, Carlos; Palmeira-de-Oliveira, Rita; Gouveia, Paula; Martinez-de-Oliveira, José

2012-01-01

The aim of this work was to study the anti-Candida activity of lidocaine and nitroglycerin alone and in combination. Ten Candida strains were included, corresponding to 1 collection type strain (ATCC 10231) and 9 clinical isolates: 4 C. albicans, 2 C. glabrata, 1 C. tropicalis, 1 C. krusei, and 1 C. parapsilosis. The CLSI reference M27-A3 micromethod was used to determine the anti-Candida activity of the drugs alone; minimal inhibitory and lethal concentrations were determined. The classic checkboard technique was used to determine the activity of combined drugs. Lidocaine fungicidal effect was dosedependent. Nitroglycerin exhibited a higher effect. The drugs combination resulted in a reduction of the inhibitory concentration, corresponding to an additive effect. In conclusion, both drugs exhibited an interesting anti-Candida activity. The combination of lidocaine with nitroglycerin was shown to have an additive effect against Candida spp., predicting the interest to include, in the future, these drugs in a new delivery system for the treatment of mucocutaneous candidosis. PMID:22675243

A new sensitizer DVDMS combined with multiple focused ultrasound treatments: an effective antitumor strategy

NASA Astrophysics Data System (ADS)

Xiong, Wenli; Wang, Pan; Hu, Jianmin; Jia, Yali; Wu, Lijie; Chen, Xiyang; Liu, Quanhong; Wang, Xiaobing

2015-12-01

Sonodynamic therapy (SDT) was developed as a promising noninvasive approach. The present study investigated the antitumor effect of a new sensitizer (sinoporphyrin sodium, referred to as DVDMS) combined with multiple ultrasound treatments on sarcoma 180 both in vitro and in vivo. The combined treatment significantly suppressed cell viability, potentiated apoptosis, and markedly inhibited angiogenesis in vivo. In vivo, the tumor weight inhibition ratio reached 89.82% fifteen days after three sonication treatments plus DVDMS. This effect was stronger than one ultrasound alone (32.56%) and than one round of sonication plus DVDMS (59.33%). DVDMS combined with multiple focused ultrasound treatments initiated tumor tissue destruction, induced cancer cell apoptosis, inhibited tumor angiogenesis, suppressed cancer cell proliferation, and decreased VEGF and PCNA expression levels. Moreover, the treatment did not show obvious signs of side effects or induce a drop in body weight. These results indicated that DVDMS combined with multiple focused ultrasounds may be a promising strategy against solid tumor.

Synergistic Antitumor Effect of Oligogalacturonides and Cisplatin on Human Lung Cancer A549 Cells.

PubMed

Huang, Cian-Song; Huang, Ai-Chun; Huang, Ping-Hsiu; Lo, Diana; Wang, Yuh-Tai; Wu, Ming-Chang

2018-06-14

Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.

The effects of noncontingent music and response interruption and redirection on vocal stereotypy.

PubMed

Gibbs, Ashley R; Tullis, Christopher A; Thomas, Raven; Elkins, Brittany

2018-06-17

Vocal stereotypy is a commonly occurring challenging behavior in children with autism spectrum disorder (ASD) that is frequently maintained by automatic reinforcement and often interferes with skill acquisition. Matched stimulation (MS), and response interruption and redirection (RIRD) are two interventions that have been demonstrated to be effective in reducing the occurrence of vocal stereotypy with participants with ASD. The current study sought to determine if the combination of MS (noncontingent music) and RIRD was more effective at reducing vocal stereotypy than RIRD alone and if the parents of children with ASD found the combination of MS and RIRD more socially valid than RIRD alone. The results suggested that the combined intervention resulted in greater suppression of vocal stereotypy and increased occurrences of on-task behavior in both participants. Additionally, RIRD required fewer implementations and had a shorter duration when combined with MS. Results suggest that the combination of MS and RIRD may be an effective intervention outside of highly controlled settings. © 2018 Society for the Experimental Analysis of Behavior.

Effective and safe mannitol administration in patients undergoing supratentorial tumor surgery: A prospective, randomized and double blind study.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Karabulut, Esra Sultan; Koksal, Serdar Selcuk; Altindas, Fatis; Tunali, Yusuf

2017-08-01

Although osmotic diuresis with mannitol is commonly used to provide brain relaxation, there is no consensus regarding its optimal dose and combination with loop diuretics. The aim of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity in patients undergoing supratentorial tumor surgery. This prospective, randomized, double blind, placebo-controlled study included 51 patients (ASA I-III) scheduled for elective supratentorial craniotomy. Different doses and combinations of diuretics were administered after the bone flap removal. The Group 1 received mannitol at 0.5gkg -1 and furosemide at 0.5mgkg -1 , the Group 2 received mannitol at 1gkg -1 and furosemide at 0.5mgkg -1 , and the Group 3 received mannitol at 0.5gkg -1 and placebo. The primary end-point of the present study is to evaluate the effects of mannitol and combination of furosemide with different doses of mannitol on brain relaxation and the secondary end-points are to evaluate their effects on blood electrolytes, lactate level, urine output, fluid balance and blood osmolarity. This study shows that mannitol alone (0.5gkg -1 ), and the combinations of furosemide (0.5mgkg -1 ) with different doses of mannitol (0.5gkg -1 -1gkg -1 ) provides adequate brain relaxation. However, administration of furosemide with low or high doses of mannitol may cause reduction in the sodium and chloride levels as well as rise in the lactate level. Moreover it may cause high urine output and negative intra-operative fluid balance. Administration of 0.5gkg -1 mannitol provides adequate brain relaxation without causing systemic side effects in patients undergoing supratentorial tumor surgery. This study is registered to clinical trials (Clinical Trials.gov identifier NCT02712476). Copyright © 2017 Elsevier B.V. All rights reserved.

Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin.

PubMed

Mason, R Preston; Dawoud, Hazem; Jacob, Robert F; Sherratt, Samuel C R; Malinski, Tadeusz

2018-07-01

The endothelium exerts many vasoprotective effects that are largely mediated by release of nitric oxide (NO). Endothelial dysfunction represents an early but reversible step in atherosclerosis and is characterized by a reduction in the bioavailability of NO. Previous studies have shown that eicosapentaenoic acid (EPA), an omega-3 fatty acid (O3FA), and statins individually improve endothelial cell function, but their effects in combination have not been tested. Through a series of in vitro experiments, this study evaluated the effects of a combined treatment of EPA and the active metabolite of atorvastatin (ATM) on endothelial cell function under conditions of oxidative stress. Specifically, the comparative and time-dependent effects of these agents on endothelial dysfunction were examined by measuring the levels of NO and peroxynitrite (ONOO - ) released from human umbilical vein endothelial cells (HUVECs). The data suggest that combined treatment with EPA and ATM is beneficial to endothelial function and was unique to EPA and ATM since similar improvements could not be recapitulated by substituting another O3FA docosahexaenoic acid (DHA) or other TG-lowering agents such as fenofibrate, niacin, or gemfibrozil. Comparable beneficial effects were observed when HUVECs were pretreated with EPA and ATM before exposure to oxidative stress. Interestingly, the kinetics of EPA-based protection of endothelial function in response to oxidation were found to be significantly different than those of DHA. Lastly, the beneficial effects on endothelial function generated by combined treatment of EPA and ATM were reproduced when this study was expanded to an ex vivo model utilizing rat glomerular endothelial cells. Taken together, these findings suggest that a combined treatment of EPA and ATM can inhibit endothelial dysfunction that occurs in response to conditions such as hyperglycemia, oxidative stress, and dyslipidemia. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

[The clinical study on labor pain relief using two kinds of segmental block anesthesia].

PubMed

Zhang, Z; Zhang, Y; Bi, L

1998-07-01

To study the pain relief effectiveness of combined subarachnoid peridural segmental block and simple peridural anesthesia, and their influences on the mothers and the infants. 100 pregnants women were administered combined subarachnoid and peridural segmental block during labor and delivery (study group). 40 pregnant women received simple peridural anesthesia (control group). The degree of labour pain, side effects, labor course, the mode of delivery and the incidences of postpartum hemorrhage, fetal distress and neonatal asphyxia were observed in two groups respectively. The pain relief effect in the study group was much better than that of the control group (P < 0.01). There were no significant differences of the mean time of labor course and the mode of delivery between the two groups (P > 0.05). The incidences of postpartum hemorrhage, fetal distress and neonatal asphyxia were similar (P > 0.05). The analgesic delivery of combined subarachnoid and peridural segmental block is safe and effective, which has no influences on the labour course and the mothers and infants. Its pain relief effectiveness is more positive and satisfactory than that of simple peridural anesthesia. We suggest that it should be performed in the medical units under optimal conditions.

Evaluating Temporal Factors in Combined Interventions of Workforce Shift and School Closure for Mitigating the Spread of Influenza

PubMed Central

Zhang, Tianyou; Fu, Xiuju; Ma, Stefan; Xiao, Gaoxi; Wong, Limsoon; Kwoh, Chee Keong; Lees, Michael; Lee, Gary Kee Khoon; Hung, Terence

2012-01-01

Background It is believed that combined interventions may be more effective than individual interventions in mitigating epidemic. However there is a lack of quantitative studies on performance of the combination of individual interventions under different temporal settings. Methodology/Principal Findings To better understand the problem, we develop an individual-based simulation model running on top of contact networks based on real-life contact data in Singapore. We model and evaluate the spread of influenza epidemic with intervention strategies of workforce shift and its combination with school closure, and examine the impacts of temporal factors, namely the trigger threshold and the duration of an intervention. By comparing simulation results for intervention scenarios with different temporal factors, we find that combined interventions do not always outperform individual interventions and are more effective only when the duration is longer than 6 weeks or school closure is triggered at the 5% threshold; combined interventions may be more effective if school closure starts first when the duration is less than 4 weeks or workforce shift starts first when the duration is longer than 4 weeks. Conclusions/Significance We therefore conclude that identifying the appropriate timing configuration is crucial for achieving optimal or near optimal performance in mitigating the spread of influenza epidemic. The results of this study are useful to policy makers in deliberating and planning individual and combined interventions. PMID:22403634

Neurotoxicity induced by methamphetamine-heroin combination in PC12 cells.

PubMed

Tian, Xiang; Ru, Qin; Xiong, Qi; Yue, Kai; Chen, Lin; Ma, Baomiao; Gan, Weimin; Si, Yuanren; Xiao, Huqiao; Li, Chaoying

2017-04-24

Simultaneous administration of psychostimulants and opioids is a major drug abuse problem worldwide. The combination of psychostimulants and opioids produces more serious effects than either drug alone and is responsible for numerous deaths. In recent years, owing to its increased use, methamphetamine (METH), a psychostimulant, has become a popular choice for use in combination with opioids, especially heroin. However, little is known about the neurotoxicity of METH/heroin combination. The aims of this study were to evaluate whether METH/heroin combination was more neurotoxic than either drug alone and analyze the possible neurotoxic mechanisms using rat pheochromocytoma (PC12) cells. Our data showed that METH/heroin combination exhibited a significant decrease in cell viability than either drug alone, and the coefficient of drug interaction (CDI) indicated that the combination appeared to produce synergistic effects. Further studies showed that METH/heroin combination induced apoptosis and decreased the mitochondrial potential significantly, compared to either drug alone. This was demonstrated by a significant decrease in the expression of Bcl-2 and an increase in expression of Bax, accompanied by increase in the activities of caspase-3 and caspase-9. These results suggest that the combination of METH and heroin is more neurotoxic than either drug alone, and it induces apoptosis via the mitochondrial apoptotic pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Synergistic Fungistatic Effects of Lactoferrin in Combination with Antifungal Drugs against Clinical Candida Isolates

PubMed Central

Kuipers, M. E.; de Vries, H. G.; Eikelboom, M. C.; Meijer, D. K. F.; Swart, P. J.

1999-01-01

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg · ml−1. Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated. PMID:10543740

Synergistic fungistatic effects of lactoferrin in combination with antifungal drugs against clinical Candida isolates.

PubMed

Kuipers, M E; de Vries, H G; Eikelboom, M C; Meijer, D K; Swart, P J

1999-11-01

Because of the rising incidence of failures in the treatment of oropharyngeal candidosis in the case of severely immunosuppressed patients (mostly human immunodeficiency virus [HIV]-infected patients), there is need for the development of new, more effective agents and/or compounds that support the activity of the common antifungal agents. Since lactoferrin is one of the nonspecific host defense factors present in saliva that exhibit antifungal activity, we studied the antifungal effects of human, bovine, and iron-depleted lactoferrin in combination with fluconazole, amphotericin B, and 5-fluorocytosine in vitro against clinical isolates of Candida species. Distinct antifungal activities of lactoferrin were observed against clinical isolates of Candida. The MICs generally were determined to be in the range of 0.5 to 100 mg. ml(-1). Interestingly, in the combination experiments we observed pronounced cooperative activity against the growth of Candida by using lactoferrin and the three antifungals tested. Only in a limited concentration range was minor antagonism detected. The use of lactoferrin and fluconazole appeared to be the most successful combination. Significant reductions in the minimal effective concentrations of fluconazole were found when it was combined with a relatively low lactoferrin concentration (1 mg/ml). Such combinations still resulted in complete growth inhibition, while synergy of up to 50% against several Candida species was observed. It is concluded that the combined use of lactoferrin and antifungals against severe infections with Candida is an attractive therapeutic option. Since fluconazole-resistant Candida species have frequently been reported, especially in HIV-infected patients, the addition of lactoferrin to the existing fluconazole therapy could postpone the occurrence of species resistance against fluconazole. Clinical studies to further elucidate the potential utility of this combination therapy have been initiated.

Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).

PubMed

Kim, Kyung-Jin; Kim, Sang-Hyun; Yoon, Young Won; Rha, Seung-Woon; Hong, Soon-Jun; Kwak, Choong-Hwan; Kim, Weon; Nam, Chang-Wook; Rhee, Moo-Yong; Park, Tae-Ho; Hong, Taek-Jong; Park, Sungha; Ahn, Youngkeun; Lee, Namho; Jeon, Hui-Kyung; Jeon, Dong-Woon; Han, Kyoo-Rok; Moon, Keon-Woong; Chae, In-Ho; Kim, Hyo-Soo

2016-10-01

We aimed to compare the effects of fixed-dose combinations of ezetimibe plus rosuvastatin to rosuvastatin alone in patients with primary hypercholesterolemia, including a subgroup analysis of patients with diabetes mellitus (DM) or metabolic syndrome (MetS). This multicenter eight-week randomized double-blind phase III study evaluated the safety and efficacy of fixed-dose combinations of ezetimibe 10 mg plus rosuvastatin, compared with rosuvastatin alone in patients with primary hypercholesterolemia. Four hundred and seven patients with primary hypercholesterolemia who required lipid-lowering treatment according to the ATP III guideline were randomized to one of the following six treatments for 8 weeks: fixed-dose combinations with ezetimibe 10 mg daily plus rosuvastatin (5, 10, or 20 mg daily) or rosuvastatin alone (5, 10, or 20 mg daily). Fixed-dose combination of ezetimibe plus rosuvastatin significantly reduced LDL cholesterol, total cholesterol, and triglyceride levels compared with rosuvastatin alone. Depending on the rosuvastatin dose, these fixed-dose combinations of ezetimibe plus rosuvastatin provided LDL cholesterol, total cholesterol, and triglyceride reductions of 56%-63%, 37%-43%, and 19%-24%, respectively. Moreover, the effect of combination treatment on cholesterol levels was more pronounced in patients with DM or MetS than in non-DM or non-MetS patients, respectively, whereas the effect of rosuvastatin alone did not differ between DM vs non-DM or MetS vs non-MetS patients. Fixed-dose combinations of ezetimibe and rosuvastatin provided significantly superior efficacy to rosuvastatin alone in lowering LDL cholesterol, total cholesterol, and triglyceride levels. Moreover, the reduction rate was greater in patients with DM or MetS. © 2016 The Authors Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.

Lapatinib in combination with paclitaxel plays synergistic antitumor effects on esophageal squamous cancer.

PubMed

Guo, Xiao-Fang; Li, Sai-Sai; Zhu, Xiao-Fei; Dou, Qiao-Hua; Liu, Duan

2018-06-16

Paclitaxel-based chemoradiotherapy was proven to be efficacious in treating patients with advanced esophageal cancer. However, the toxicity and the development of resistance limited its anticancer efficiency. The present study was to evaluate the antitumor effects of lapatinib, a dual tyrosine inhibitor of both epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), combined with paclitaxel on the esophageal squamous cancer. MTT assays were used to evaluate the effects of the combination of lapatinib and paclitaxel on the growth of esophageal squamous cancer cell lines (KYSE150, KYSE450, KYSE510 and TE-7). The activity of the combination of two agents on cell invasion, migration and apoptosis was measured by wound healing assay, transwell assay and Annexin V-FITC/PI stain assay. Western blot assay was used to analyze the effects of the two agents on the EGFR/HER2 signaling. The in vivo efficacy was evaluated in KYSE450 xenograft nude mouse model. The combination of lapatinib and paclitaxel was highly synergistic in inhibiting cell growth with a combination index of < 1, and suppressed significantly the invasion and migration capability of esophageal squamous cancer cells. Esophageal squamous cancer cells displayed increased rates of apoptosis after treatment with lapatinib plus paclitaxel. The phosphorylated EGFR and HER2 as well as the activation of downstream molecules MAPKs and AKT significantly decreased when exposed to lapatinib and paclitaxel. In vivo studies showed that the combination of two agents had greater antitumor efficacy than either agent alone. The combination of lapatinib with paclitaxel showed synergistic antitumor activity, suggesting their potential in treating patients with esophageal squamous cancer.

Effects of Platinum Nanocolloid in Combination with Gamma Irradiation on Normal Human Esophageal Epithelial Cells.

PubMed

Li, Qiang; Tanaka, Yoshiharu; Saitoh, Yasukazu; Miwa, Nobuhiko

2016-05-01

Our previous study demonstrated that platinum nanocolloid (Pt-nc), combined with lower-dose gamma irradiation at 3, 5, and 7 Gy significantly decreased proliferation and accelerated apoptosis of the human esophageal squamous cell carcinoma-derived cell line KYSE-70. The aim of the present study was to determine, under the same conditions as our previous study where gamma rays combined with Pt-nc were carcinostatic to KYSE-70 cells, if we could induce a radioprotective or the radiation-sensitizing effect on the human normal esophageal epithelial cells (HEEpiC). HEEpiC were treated with various Pt-nc concentrations and then irradiated with various gamma-ray doses. The proliferative status of HEEpiC was evaluated using trypan blue dye-exclusion and WST-8 assays. The cellular and nucleic morphological features were determined using crystal violet and Hoechst 33342 stainings, respectively. The intracellular level of reactive oxygen species (ROS) in HEEpiC was evaluated with a nitro blue tetrazolium (NBT) assay. The apoptotic status was detected with caspase-3, Bax, and Bcl-2 by Western blotting. Either Pt-nc or gamma irradiation could inhibit the growth of HEEpiC; however, their combined use exerted a significant proliferation-inhibitory effect in a Pt-nc dose-dependent manner than gamma irradiation alone. Pt-nc resulted in radiation sensitization rather than radiation protection on HEEpiC in vitro similar to KYSE-70 cells, when Pt-nc was administrated alone or combined with gamma irradiation. Thus, Pt-nc has an inhibitory effect on cell proliferation, a facilitative effect on apoptosis, and a certain degree of toxicity against HEEpiC.

Antiproliferative and proapoptotic effects of topotecan in combination with thymoquinone on acute myelogenous leukemia.

PubMed

Khalife, Rana; El-Hayek, Stephany; Stephany, El-Hayek; Tarras, Omayr; Hodroj, Mohammad Hassan; Rizk, Sandra

2014-09-01

Topotecan has shown promising antineoplastic activity in solid tumors and acute leukemia. Because of the primary dose-limiting toxicity of topotecan, it is necessary to identify other agents that can work synergistically with topotecan, potentially increasing its efficacy while limiting its toxicity. Many studies showed synergism in combination of topotecan with gemcitabine and bortezomib. Other studies report the increase in growth inhibition of gemcitabine or oxaliplatin when cells were preexposed to naturally occurring drugs such as thymoquinone. The aim of this project was to study the mode of action of topotecan along with thymoquinone, on survival and apoptosis pathways in acute myelogenous leukemia (AML) cell lines, and to investigate the potential synergistic effect of thymoquinone on topotecan. U937 cells were incubated with different topotecan and thymoquinone concentrations for 24 and 48 hours, separately and in combination. Cell proliferation was determined using WST-1 (Roche) reagent. The effect of the compounds on protein expression of Bax, Bcl2, p53, caspase-9, -8, and -3 was determined using Western blot analysis. Cell cycle analysis was performed in addition to annexin/propidium iodide staining. Thymoquinone and topotecan exhibited antiproliferative effects on U937 cells when applied separately. In combination, the reduction in proliferation was extremely significant with a major increase in the expression levels of Bax/Bcl2, p53, and caspase-3 and -9. Preexposure with thymoquinone resulted in an increase in cell growth inhibition compared with topotecan treatment. Thymoquinone, when combined with topotecan in noncytotoxic doses, produced synergistic antiproliferative and proapoptotic effects in AML cells. Preexposure to thymoquinone seems to be more effective than simultaneous application with topotecan. Copyright © 2014 Elsevier Inc. All rights reserved.

Combined effects of photodynamic therapy and irrigants in disinfection of root canals.

PubMed

Susila, Anand V; Sugumar, R; Chandana, C S; Subbarao, C V

2016-06-01

In this study, the combined effects of photodynamic therapy and irrigants in eradicating common endodontic pathogens are evaluated. Roots of 80 extracted single rooted teeth are divided into 2 groups (1) mechanical flushing; (2) antibacterial irrigation. After cleaning and shaping, they are inoculated with either (A) Streptococcus mutans or (B) Enterococcus faecalis and incubated. They are again subdivided and either only irrigated or irrigated and lased. Dentin shavings are taken from root canal walls and cultured. Statistical analysis using One-Way ANOVA and Post-hoc tests are done. The combination eradicated both bacteria. Antibacterial irrigants controlled S. mutans better than PDT (p = 0.041). The combination of PDT and antibacterial irrigation proposed in this study can be used in all primary cases for thorough and reliable disinfection of root canals but may be highly effective in resistant cases like endodontic failures, as E. faecalis is prevalent in such cases. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synergistic effects and related bioactive mechanisms of Potentilla fruticosa Linn. leaves combined with green tea polyphenols studied with microbial test system (MTS).

PubMed

Liu, Ze-Hua; Luo, Zi-Wen; Li, Deng-Wu; Wang, Dong-Mei; Ji, Xia

2018-06-01

Previous research found Potentilla fruticosa leaf extracts (PFE) combined with green tea polyphenols (GTP) showed obvious synergistic effects based on chemical mechanisms. This study further confirmed the synergy of PFE + GTP viewed from bioactivities using the microbial test system (MTS). The MTS antioxidant activity results showed the combination of PFE + GTP exhibited synergistic effect and the ratio 3:1 showed the strongest synergy, which were in accordance with the results in H 2 O 2 production rate. The combination of PFE + GTP promoted CAT and SOD enzyme activity and their gene expression especially at the ratio 3:1. Therefore, the synergism of PFE + GTP may be due to the promotion of CAT and SOD genes expression which enhanced the CAT and SOD enzyme activities. These results confirmed the synergy of PFE + GTP and could provide theoretical basis to produce a compounded tea made of a mixture of leaves from Potentilla species.

Investigation of the synergistic effects of haloperidol combined with Calculus Bovis Sativus in treating MK-801-induced schizophrenia in rats

PubMed Central

Lei, Kai; He, Guo-Fang; Zhang, Cheng-Liang; Liu, Ya-Nan; Li, Juan; He, Guang-Zhao; Li, Xi-Ping; Ren, Xiu-Hua; Liu, Dong

2017-01-01

Clinical studies that focused on treating schizophrenia showed that Calculus Bovis Sativus (CBS), a substitute of Calculus Bovis, when used in combination with haloperidol could significantly lower the dosage of haloperidol compared with treatment with haloperidol alone, whereas efficacy was maintained. The aim of this study was to investigate the synergetic anti-schizophrenia effects in rats using CBS in combination with haloperidol. An open field test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and haloperidol on MK-801-induced schizophrenic rats. Rat plasma concentrations of intragastric haloperidol and intravenous haloperidol were determined after oral administration of a single dose or 1-week of pretreatment with CBS (50 mg/kg). The pharmacodynamic data showed a significant decrease in locomotor activity and an increase in the percentage of the central distance when haloperidol was concomitantly administered with CBS compared with haloperidol administration alone. The AUC0-∞ and Cmax of haloperidol in the orally coadministered groups were significantly higher compared with the oral treatment with haloperidol alone. In conclusion, oral coadministration of CBS with haloperidol resulted in a synergistic effect in rats. The enhanced oral bioavailability of haloperidol when combined with CBS might be attributed to the interaction between them. PMID:29225304

Cranberry Juice and Combinations of Its Organic Acids Are Effective against Experimental Urinary Tract Infection.

PubMed

Jensen, Heidi D; Struve, Carsten; Christensen, Søren B; Krogfelt, Karen A

2017-01-01

The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder ( P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced ( P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice ( P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together ( P < 0.001), and so did the combination of malic plus citric acid ( P < 0.01) and malic plus quinic acid ( P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.

Induction of Early Autophagic Process on Leishmania amazonensis by Synergistic Effect of Miltefosine and Innovative Semi-synthetic Thiosemicarbazone

PubMed Central

Scariot, Débora B.; Britta, Elizandra A.; Moreira, Amanda L.; Falzirolli, Hugo; Silva, Cleuza C.; Ueda-Nakamura, Tânia; Dias-Filho, Benedito P.; Nakamura, Celso V.

2017-01-01

Drug combination therapy is a current trend to treat complex diseases. Many benefits are expected from this strategy, such as cytotoxicity decrease, retardation of resistant strains development, and activity increment. This study evaluated in vitro combination between an innovative thiosemicarbazone molecule – BZTS with miltefosine, a drug already consolidated in the leishmaniasis treatment, against Leishmania amazonensis. Cytotoxicity effects were also evaluated on macrophages and erythrocytes. Synergistic antileishmania effect and antagonist cytotoxicity were revealed from this combination therapy. Mechanisms of action assays were performed in order to investigate the main cell pathways induced by this treatment. Mitochondrial dysfunction generated a significant increase of reactive oxygen and nitrogen species production, causing severe cell injuries and promoting intense autophagy process and consequent apoptosis cell death. However, this phenomenon was not strong enough to promote dead in mammalian cell, providing the potential selective effect of the tested combination for the protozoa. Thus, the results confirmed that drugs involved in distinct metabolic routes are promising agents for drug combination therapy, promoting a synergistic effect. PMID:28270805

Cost-Effectiveness of Nivolumab-Ipilimumab Combination Therapy Compared to Monotherapy for First-Line Treatment of Metastatic Melanoma in the United States

PubMed Central

Oh, Anna; Tran, Dang M; McDowell, Leann C; Keyvani, Dor; Barcelon, Jay Andrew; Merino, Oscar; Wilson, Leslie

2018-01-01

BACKGROUND The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations to third-party payer systems, physicians, and patients. OBJECTIVE Develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first-line therapy in metastatic melanoma while accounting for differential effectiveness in PD-L1 positive and negative patients. METHODS A three-state Markov model (‘PD-L1 positive stable disease’, ‘PD-L1 negative stable disease’, and ‘Progression and/or Death’) was developed using a US societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 US dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS Nivolumab-ipilimumab combination therapy is not the cost effective choice ($454,092 per progression-free quality-adjusted-life-year [PFQALY]) compared to nivolumab monotherapy in our base case analysis at a willingness-to-pay threshold of $100,000/PFQALY. Both combination therapy and nivolumab monotherapy were cost-effective choices compared to ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment but combination therapy had an improved ICER of $295,903/PFQALY. Combination therapy became dominated by nivolumab when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to <$21,555 per dose for combination therapy to have an ICER <$100,000/PFQALY, and to <$19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS Nivolumab-ipilimumab combination therapy is not cost-effective compared to nivolumab monotherapy, which is the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions and future cost-effectiveness studies are completed. PMID:28530525

A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD.

PubMed

Li, Li; Yang, Li; Zhuo, Chuan-jun; Wang, Yu-Feng

2013-08-22

To evaluate the efficacy of combined methylphenidate and EEG feedback treatment for children with ADHD. Forty patients with ADHD were randomly assigned to the combination group (methylphenidate therapy and EEG feedback training) or control group (methylphenidate therapy and non-feedback attention training) in a 1:1 ratio using the double-blind method. These patients, who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years, had obtained optimal therapeutic effects by titrating the methylphenidate dose prior to the trial. The patients were assessed using multiple parameters at baseline, after 20 treatment sessions, after 40 treatment sessions, and in 6-month follow-up studies. Compared to the control group, patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions. The combination of EEG feedback and methylphenidate treatment is more effective than methylphenidate alone. The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects.

Rationale of combination therapy with antioxidants in medical management of Peyronie’s disease: results of clinical application

PubMed Central

Paulis, Gianni; Paulis, Andrea; Romano, Gennaro; Barletta, Davide; Fabiani, Andrea

2017-01-01

Peyronie’s disease (PD) is a connective tissue disorder involving the tunica albuginea of the corpora cavernosa of the penis. We have published several studies describing a “combined therapy” for PD patients, but the present study aims to clearly demonstrate how the association between various antioxidants in PD treatment can significantly increase the likelihood of therapeutic success. We used the following substances: silymarin, ginkgo biloba, vitamin E, bilberry, topical diclofenac sodium, and pentoxifylline (PTX). We analyzed the therapeutic impact and possible side effects of one or more antioxidants in patients with early-stage PD. To clearly prove that it is possible to achieve better results when combining more than one agent, we designed this study with five treatment groups, corresponding, respectively, to the administration of a single oral antioxidant; two oral antioxidants; three oral antioxidants; five oral antioxidants + local diclofenac; and five oral antioxidants + local diclofenac + PTX by perilesional injection. One hundred and twenty patients were assigned to five groups of treatment designed according to the abovementioned study aim. Outcomes after 6 months of treatment showed that combined antioxidant therapy is effective in treating PD. Statistical analysis showed significant differences between the treatment groups with regard to: improvement and disappearance of penile pain; percentage of reduction in the volume of penile plaque; reduction in penile curvature; recovery of erectile function in patients with erectile dysfunction; increase in the International Index of Erectile Function score; and reduction of psychosexual impact. Furthermore, we observed that the clinical efficacy of combined therapy is greater when topical use of diclofenac gel and perilesional injection of PTX are added to oral treatment with more than one antioxidant. Although several articles have already been published reporting the effectiveness of combined treatment in PD, this is the first study clearly proving how, as the number of substances used in treatment rises, a proportionally greater therapeutic effect is achieved. PMID:28791261

Combined treatment with Dendrobium candidum and black tea extract promotes osteoprotective activity in ovariectomized estrogen deficient rats and osteoclast formation.

PubMed

Wang, Ming-Yue; Shen, Chang; An, Meng-Fei; Xie, Chuan-Qi; Wu, Xin; Zhu, Qiang-Qiang; Sun, Bin; Huang, Yan-Ping; Zhao, Yun-Li; Wang, Xuan-Jun; Sheng, Jun

2018-05-01

Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected. Results showed that OVX rats that were treated orally with a DC and BTE combination for 12 weeks maintained their calcium (Ca) and phosphorus (P) homeostasis and exhibited significantly enhanced estradiol (E 2 ) and OPG levels. This combination treatment also simultaneously reduced levels of interleukin (IL)-1β, IL-6 and improved the organ coefficients of the uterus and femur as well as BMD and BMC in OVX rats. In addition, this DC and BTE combination suppressed osteoclast differentiation in the RANKL-stimulated osteoclastogenesis of RAW 264.7 cells and effectively inhibited the expression of osteoclast-associated genes and proteins. The results of this study further highlight the fact that a combination of DC and BTE improved ovariectomy-induced osteoporosis in rats and suppressed RANKL-stimulated osteoclastogenesis in RAW 264.7 cells. This combination also significantly alleviated osteoporosis when compared to the alternative sole treatments above, due to synergistic effects among components. One partial mechanism of this combination might be the inhibition of osteoclast proliferation and the regulation of NFATC1/c-Fos expression. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of caffeine, caffeic acid and their various combinations on enzymes of cholinergic, monoaminergic and purinergic systems critical to neurodegeneration in rat brain-In vitro.

PubMed

Akomolafe, S F; Akinyemi, A J; Ogunsuyi, O B; Oyeleye, S I; Oboh, G; Adeoyo, O O; Allismith, Y R

2017-09-01

Caffeine and caffeic acid are two bioactive compounds that are present in plant foods and are major constituent of coffee, cocoa, tea, cola drinks and chocolate. Although not structurally related, caffeine and caffeic acid has been reported to elicit neuroprotective properties. However, their different proportional distribution in food sources and possible effect of such interactions are not often taken into consideration. Therefore, in this study, we investigated the effect of caffeine, caffeic acid and their various combinations on activities of some enzymes [acetylcholinesterase (AChE), monoamine oxidase (MAO) ecto-nucleoside triphosphate diphosphohydrolase (E-NTPase), ecto-5 1 -nucleotidase (E-NTDase) and Na + /K + ATPase relevant to neurodegeneration in vitro in rat brain. The stock concentration of caffeine and caffiec acid and their various proportional combinations were prepared and their interactions with the activities of these enzymes were assessed (in vitro) in different brain structures. The Fe 2+ and Cu 2+ chelating abilities of the samples were also investigated. The results revealed that caffeine, caffeic acid and their various combinations exhibited inhibitory effect on activities of AChE, MAO, E-NTPase and E-NTDase, but stimulatory effect on Na + /K + ATPase activity. The combinations also exhibited Fe 2+ and Cu 2+ chelating abilities. Considering the various combinations, a higher caffeine to caffeic acid ratio produced significantly highest enzyme modulatory effects; these were significantly lower to the effect of caffeine alone but significantly higher than the effect of caffeic acid alone. These findings may provide new insight into the effect of proportional combination of these bioactive compounds as obtained in many foods especially with respect to their neuroprotective effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Plumbagin improves the efficacy of androgen deprivation therapy in prostate cancer: A pre-clinical study.

PubMed

Abedinpour, Parisa; Baron, Véronique T; Chrastina, Adrian; Rondeau, Gaelle; Pelayo, Jennifer; Welsh, John; Borgström, Per

2017-12-01

Plumbagin is a candidate drug for the treatment of prostate cancer. Previous observations indicated that it may improve the efficacy of androgen deprivation therapy (ADT). This study evaluates the effectiveness of treatment with combinations of plumbagin and alternative strategies for ADT in mouse models of prostate cancer to support its clinical use. Plumbagin was administered per oral in a new sesame oil formulation. Standard toxicology studies were performed in rats. For tumor growth studies, mouse prostate cancer cell spheroids were placed on top of grafted prostate tissue in a dorsal chamber and allowed to form tumors. Mice were separated in various treatment groups and tumor size was measured over time by intra-vital microscopy. Survival studies were done in mice after injection of prostate cancer cells in the prostate of male animals. Androgen receptor (AR) levels were analyzed by Western blot from prostate cancer cells treated with plumbagin. Plumbagin caused a decrease in AR levels in vitro. In mice, plumbagin at 1 mg/kg in sesame oil displayed low toxicity and caused a 50% tumor regression when combined with castration. The combination of plumbagin with various forms of chemical ADT including treatment with a GnRH receptor agonist, a GnRH receptor antagonist, or CYP17A1 inhibitors, outperformed ADT alone, increasing mouse survival compared to the standard regimen of castration alone. In contrast, the combination of plumbagin with AR antagonists, such as bicalutamide and enzalutamide, showed no improvement over AR antagonists alone. Thus, plumbagin is effective in combination with drugs that prevent the synthesis of testosterone or its conversion to dihydrotestosterone, but not with drugs that bind to AR. Plumbagin significantly improves the effect of ADT drugs currently used in the clinic, with few side effects in mice. © 2017 Wiley Periodicals, Inc.

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

PubMed

Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

2018-04-01

To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

[Electron microscope analysis of cardiomyocytes in the rat left ventricle under simulation of weightlessness effects and artificial gravitation].

PubMed

Varenik, E N; Lipina, T V; Shornikova, M V; Krasnov, I B; Chentsov, Iu S

2012-01-01

Electron microscopic study of left ventricle cardiomyocytes and quantitative analysis of their mitochondriom was performed in rats exposed to tail-suspension, as a model of weightlessness effects, to artificial gravity produced by intermittent 2G centrifugation and a combination of these effects. It was found that the cardiomyocytes ultrastructure changed slightly after tail-suspension and after intermittent 2G influence, as well as under a combination of these effects. However, the number of intermitochondrial junctions increased significantly in the interfibrillar zone of cardiomyocytes under a combination of tail-suspension and intermittent 2G influence, which agrees with the cell hypertrophy described earlier.

Effects of Combined Loads on the Nonlinear Response and Residual Strength of Damaged Stiffened Shells

NASA Technical Reports Server (NTRS)

Starnes, James H., Jr.; Rose, Cheryl A.; Rankin, Charles C.

1996-01-01

The results of an analytical study of the nonlinear response of stiffened fuselage shells with long cracks are presented. The shells are modeled with a hierarchical modeling strategy and analyzed with a nonlinear shell analysis code that maintains the shell in a nonlinear equilibrium state while the crack is grown. The analysis accurately accounts for global and local structural response phenomena. Results are presented for various combinations of internal pressure and mechanical loads, and the effects of crack orientation on the shell response are described. The effects of combined loading conditions and the effects of varying structural parameters on the stress-intensity factors associated with a crack are presented.

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

PubMed Central

Saha, Subbroto Kumar; Yin, Yingfu; Kim, Kyeongseok; Yang, Gwang-Mo; Abdal Dayem, Ahmed; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC. PMID:28498322

Concurrent Use of Cannabis and Alcohol: Neuropsychiatric Effect Consequences.

PubMed

Romaguera, Anna; Torrens, Marta; Papaseit, Esther; Arellano, Ana Lucia; Farré, Magi

2017-01-01

Concurrent use of cannabis and alcohol is frequent. According different studies, the prevalence is among 20-34% depending on different samples studied. In contrast with the wide evidence available about neuropsychiatric effects associated to the use of cannabis or alcohol separately, there are few studies of the neuropsychiatric effects of their combination. Our aim was to review the literature regarding this topic. We performed a search in MEDLINE and from 114 potentially eligible studies, 27 were selected. Most of them studied the relation between cannabis and alcohol, and with them combined to other substances of abuse, but only a few considered their concurrent effect among mental disorders (ADHD, bipolar disorder) and neuropsychological performance. More research in the neuropsychiatric effects of the concomitant use of cannabis and alcohol is needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Safety and efficacy of low-dose esterified estrogens and methyltestosterone, alone or combined, for the treatment of hot flashes in menopausal women: a randomized, double-blind, placebo-controlled study.

PubMed

Liu, James; Allgood, Adam; Derogatis, Leonard R; Swanson, Stephen; O'Mahony, Michael; Nedoss, Bertrand; Soper, Herbert; Zbella, Edward; Prokofieva, Svetlana Vladimirovna; Zipfel, Lisa; Guo, Chun-Yuan

2011-01-01

This study evaluated safety and efficacy of esterified estrogens and methyltestosterone administered alone or in combination for the treatment of hot flashes in menopausal women. The 0.30-mg esterified estrogens and 0.30-mg methyltestosterone combination was the lowest effective dose, and our results are consistent with the known safety profile of estrogen and androgen combination products. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Frondoside A potentiates the effects of conventional therapeutic agents in acute leukemia.

PubMed

Sajwani, F H; Collin, P; Adrian, T E

2017-12-01

Acute leukemia is the major cause of mortality in hematological malignancies. Despite improvement of survival with current chemotherapies, patients die from the disease or side-effects of treatment. Thus, new therapeutic agents are needed. Frondoside A is a triterpenoid glycoside originally isolated from the sea cucumber, Cucumaria frondosa that has potent antitumor effects in various cancers. The current study investigated the effects of frondoside A in acute leukemia cell lines alone and in combination with drugs used for this malignancy. This study is the first comparing the efficacy of frondoside A to available conventional drugs. The acute leukemia cell lines used were CCRF-CEM, HL-60 and THP-1. Cells were cultured and treated with different concentrations of vincristine sulphate, asparaginase and prednisolone alone and in combination with frondoside A. The inhibitory concentration 50 (IC 50 ) for each compound was determined for the cell lines. CCRF-CEM cells were very sensitive to frondoside A treatment while HL-60 and THP1 were less sensitive. Frondoside A markedly enhanced the anticancer effects of all of the conventional drugs. Synergistic effects were seen with most of the combinations. Frondoside A may be valuable in the treatment of acute leukemia, particularly when used in combination with current therapeutic drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine

PubMed Central

Marks, Katherine R.; Lile, Joshua A.; Stoops, William W.; Glaser, Paul E.A.; Hays, Lon R.; Rush, Craig R.

2016-01-01

Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric acid type A (GABAA) receptors (e.g., alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of d-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and “positive” subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone. Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6–7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected. Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like “positive” subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10 mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior. PMID:27043121

Separate and Combined Effects of Naltrexone and Extended-Release Alprazolam on the Reinforcing, Subject-Rated, and Cardiovascular Effects of Methamphetamine.

PubMed

Marks, Katherine R; Lile, Joshua A; Stoops, William W; Glaser, Paul E A; Hays, Lon R; Rush, Craig R

2016-06-01

Opioid antagonists (eg, naltrexone) and positive modulators of γ-aminobutyric acid type A receptors (eg, alprazolam) each modestly attenuate the abuse-related effects of stimulants. A previous study demonstrated that acute pretreatment with the combination of naltrexone and alprazolam attenuated a greater number of the subject-rated effects of D-amphetamine than the constituent drugs alone. This study tested the hypothesis that maintenance on the combination of naltrexone and alprazolam XR would attenuate the reinforcing and "positive" subject-rated effects of methamphetamine to a greater extent than the constituent drugs alone.Eight non-treatment-seeking, stimulant-using individuals completed a placebo-controlled, crossover, double-blind inpatient protocol. Participants were maintained on naltrexone (0 and 50 mg), alprazolam XR (0 and 1 mg), and the combination of naltrexone and alprazolam XR (50 mg and 1 mg, respectively) for 6 to 7 days. Under each maintenance condition, participants sampled intranasal doses of methamphetamine (0, 10, and 30 mg), and were then offered the opportunity to work for the sampled dose on a modified progressive-ratio procedure. Subject-rated drug effect questionnaires, psychomotor, and physiology assessments were collected.Intranasal methamphetamine functioned as a reinforcer and produced prototypical stimulant-like "positive" subject-rated and physiological effects. Maintenance on naltrexone significantly decreased the reinforcing, but not subject-rated drug effects of 10-mg methamphetamine. Alprazolam XR and the combination of naltrexone and alprazolam XR did not impact methamphetamine self-administration or subject-rated drug effects. The results support the continued evaluation of naltrexone for methamphetamine dependence, as well as the identification of other drugs that enhance its ability to reduce drug-taking behavior.

Combined effects of warming and ocean acidification on coral reef Foraminifera Marginopora vertebralis and Heterostegina depressa

NASA Astrophysics Data System (ADS)

Schmidt, Christiane; Kucera, Michal; Uthicke, Sven

2014-09-01

Warming and changes in ocean carbonate chemistry alter marine coastal ecosystems at an accelerating pace. The interaction between these stressors has been the subject of recent studies on reef organisms such as corals, bryozoa, molluscs, and crustose coralline algae. Here we investigated the combined effects of elevated sea surface temperatures and pCO2 on two species of photosymbiont-bearing coral reef Foraminifera: Heterostegina depressa (hosting diatoms) and Marginopora vertebralis (hosting dinoflagellates). The effects of single and combined stressors were studied by monitoring survivorship, growth, and physiological parameters, such as respiration, photochemistry (pulse amplitude modulation fluorometry and oxygen production), and chl a content. Specimens were exposed in flow-through aquaria for up to seven weeks to combinations of two pCO2 (~790 and ~490 µatm) and two temperature (28 and 31 °C) regimes. Elevated temperature had negative effects on the physiology of both species. Elevated pCO2 had negative effects on growth and apparent photosynthetic rate in H.depressa but a positive effect on effective quantum yield. With increasing pCO2, chl a content decreased in H. depressa and increased in M. vertebralis. The strongest stress responses were observed when the two stressors acted in combination. An interaction term was statistically significant in half of the measured parameters. Further exploration revealed that 75 % of these cases showed a synergistic (= larger than additive) interaction between the two stressors. These results indicate that negative physiological effects on photosymbiont-bearing coral reef Foraminifera are likely to be stronger under simultaneous acidification and temperature rise than what would be expected from the effect of each of the stressors individually.

Promises and Dangers of Combination Therapy.

PubMed

Kruis, Wolfgang; Nguyen, Phuong G; Morgenstern, Julia

2017-01-01

The efficiency of the existing methods of treating inflammatory bowel disease (IBD) is limited. There are 2 ways to address this problem - either create new treatment modalities or optimize current therapies. Optimisation may be accomplished by using combinations of established therapeutic strategies. With regard to topically acting compounds such as 5-aminosalicylic acid, combining oral and rectal preparations is a commonly used method. Another commonly used combination is anti-tumor necrosis factor (TNF)-α antibody modalities together with immunosuppressants (thiopurines, methotrexate). Several aspects favour those combinations such as increased effectivity, prevention of immunogenicity and perhaps less adverse events. Currently, discussion on directly additive therapeutic effects is in progress, which have been demonstrated in some clinical trials. As on date, the combination of infliximab with azathioprine is most likely the most effective treatment of Crohn's disease. On the other hand, a combination therapy with both compounds affecting the immune system has, of course, risks. For sure, the frequency with which serious infectious complications are arising is increasing. Furthermore, the number of patients experiencing malignancies such as hepato-splenic lymphoma or melanoma is strongly suspected to be on the rise. In summary, combinations of current treatments for IBD are widely established. Various strategies have been studied and significant improvements of therapeutic effects have been demonstrated. Unfortunately, some of those proven combinations increase therapeutic risks, for example, increase the frequency of serious infections and also of some malignancies. Therefore, great caution has to be exercised when applying combination therapies. © 2017 S. Karger AG, Basel.

Omega-3 and omega-6 polyunsaturated fatty acids enhance arsenic trioxide efficacy in arsenic trioxide-resistant leukemic and solid tumor cells.

PubMed

Wirtitsch, Melanie; Roth, Erich; Bachleitner-Hofmann, Thomas; Wessner, Barbara; Sturlan, Sanda

2009-01-01

Recently we showed that the polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) sensitizes arsenic trioxide (As2O3)-resistant tumor cells to a clinically achievable concentration (1 microM) of As2O3 via a reactive oxygen species (ROS)-dependent mechanism. The aim of the present study was to evaluate, whether this combined effect of As2O3 and DHA is also applicable to other PUFAs [i.e., eicospentaenoic acid (EPA), arachidonic acid (AA), and gamma-linolenic acid (GLA)]. Fourteen tumor cell lines were incubated with As2O3 (1 microM), PUFA (25-100 microM), or the combination thereof (+/- vitamin E). Cell viability (colorimetric), apoptosis (bivariate annexin V/propidium iodide staining, detection of hypodiploid DNA), and thiobarbituric acid reactive substances (TBARS) were evaluated. Twelve of 14 As2O3-resistant cell lines tested were resistant to PUFA monotherapy. However, combined treatment with As2O3 and either PUFA significantly reduced cell viability in a dose-dependent manner with AA being the most potent As2O3 enhancer. The combined cytotoxic effect of As2O3/AA treatment was due to induction of apoptosis, preceded by increased intracellular TBARS and was abolished by the antioxidant vitamin E. Importantly, the combined effect of As2O3 and AA was selectively toxic for malignant cells because no cytotoxic effect was observed in normal skin fibroblasts and human microvascular endothelial cells. In conclusion, our study shows that also other PUFAs than DHA-and in particular the omega-6-PUFA AA--can be used as effective modulators of tumor cell chemosensitivity to clinically achievable concentrations of As2O3. Enhanced lipid peroxidation most likely constitutes the key mechanism for the combined effect.

Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

PubMed

Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

2017-03-05

Clopidogrel (Plavix ® , Sanofi-Aventis), the adenosine diphosphate P2Y 12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl 3 -induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving Durability of Turbine Components Through Trenched Film Cooling and Contoured Endwalls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bogard, David G.; Thole, Karen A.

2014-09-30

The experimental and computational studies of the turbine endwall and vane models completed in this research program have provided a comprehensive understanding of turbine cooling with combined film cooling and TBC. To correctly simulate the cooling effects of TBC requires the use of matched Biot number models, a technique developed in our laboratories. This technique allows for the measurement of the overall cooling effectiveness which is a measure of the combined internal and external cooling for a turbine component. The overall cooling effectiveness provides an indication of the actual metal temperature that would occur at engine conditions, and is hencemore » a more powerful performance indicator than the film effectiveness parameter that is commonly used for film cooling studies. Furthermore these studies include the effects of contaminant depositions which are expected to occur when gas turbines are operated with syngas fuels. Results from the endwall studies performed at Penn State University and the vane model studies performed at the University of Texas are the first direct measurements of the combined effects of film cooling and TBC. These results show that TBC has a dominating effect on the overall cooling effectiveness, which enhances the importance of the internal cooling mechanisms, and downplays the importance of the film cooling of the external surface. The TBC was found to increase overall cooling effectiveness by a factor of two to four. When combined with TBC, the primary cooling from film cooling holes was found to be due to the convective cooling within the holes, not from the film effectiveness on the surface of the TBC. Simulations of the deposition of contaminants on the endwall and vane surfaces showed that these depositions caused a large increase in surface roughness and significant degradation of film effectiveness. However, despite these negative factors, the depositions caused only a slight decrease in the overall cooling effectiveness on the endwall, and in some cases a slight increase in overall cooling effectiveness on the vane model. This was attributed to the insulating effects of the depositions which compensated for the negative factors.« less

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.

PubMed

Lehmann, Christian; Friess, Thomas; Birzele, Fabian; Kiialainen, Anna; Dangl, Markus

2016-06-28

Venetoclax, a small molecule BH3 mimetic which inhibits the anti-apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for treatment of p53 wild-type AML. The effect of idasanutlin and venetoclax combination on cell viability, apoptosis, and cell cycle progression was investigated in vitro using established AML cell lines. In vivo efficacy was demonstrated in subcutaneous and orthotopic xenograft models generated in female nude or non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Mode-of-action analyses were performed by means of cell cycle kinetic studies, RNA sequencing as well as western blotting experiments. Combination treatment with venetoclax and idasanutlin results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles. Combination treatment with venetoclax removed this dependency, resulting in an acceleration of cell death kinetics. As expected, gene expression studies using RNA sequencing showed significant alterations to pathways associated with p53 signaling and cell cycle arrest (CCND1 pathway) in response to idasanutlin treatment. Only few gene expression changes were observed for venetoclax treatment and combination treatment, indicating that their effects are mediated mainly at the post-transcriptional level. Protein expression studies demonstrated that inhibition of the anti-apoptotic protein Mcl-1 contributed to the activity of venetoclax and idasanutlin, with earlier inhibition of Mcl-1 in response to combination treatment contributing to the superior combined activity. The role of Mcl-1 was confirmed by small hairpin RNA gene knockdown studies. Our findings provide functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies.

Effects of Drugs and Drug Combinations in Pigeons Trained to Discriminate among Pentobarbital, Dizocilpine, a Combination of These Drugs, and Saline

ERIC Educational Resources Information Center

McMillan, D. E.; Wessinger, William D.; Li, Mi

2009-01-01

Drugs with multiple actions can have complex discriminative-stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four-choice procedure…

Interventions combining motivational interviewing and cognitive behaviour to promote medication adherence: a literature review.

PubMed

Spoelstra, Sandra L; Schueller, Monica; Hilton, Melissa; Ridenour, Kimberly

2015-05-01

This article presents an integrative review of the evidence for combined motivational interviewing and cognitive behavioural interventions that promote medication adherence. We undertook this review to establish a scientific foundation for development of interventions to promote medication adherence and to guide clinical practice. The World Health Organization has designated medication adherence as a global problem. Motivational interviewing and cognitive behaviour interventions have been found to individually promote medication adherence. However, there is a gap in the literature on the effect of combined motivational interviewing and cognitive behavioural approaches to promote medication adherence. Integrative review. COCHRANE, PubMed and CINAHL were searched to access relevant studies between 2004-2014. Inclusion criteria were interventions combining motivational interviewing and cognitive behavioural therapy with medication adherence as the outcome. Articles were assessed for measures of adherence and methodological rigour. Analysis was performed using an integrative review process. Six articles met the inclusion criteria. A randomised controlled trial reported pretreatment missed doses of 5·58 and post-treatment of 0·92 and trended towards significance. Four cohort studies had effect sizes of 0·19-0·35 (p < 0·05). A case study had a pretreatment adherence rate of 25% and post-treatment 77% (p < 0·01). Although there were a limited number of studies on combined motivational interviewing and cognitive behavioural interventions, five out of six were effective at improving medication adherence. Future studies with large rigorous randomised trials are needed. This review provides clinicians with the state of the science in relation to combined motivational interviewing and cognitive behavioural therapy interventions that promote medication adherence. A summary of intervention components and talking points are provided to aid nurses in informing decision-making and translating evidence into practice. © 2014 John Wiley & Sons Ltd.

Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users

PubMed Central

Marks, Katherine R.; Lile, Joshua A.; Stoops, William W.

2014-01-01

Rationale Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds. Objectives The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone. Methods Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected. Results Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone. Conclusions The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration. PMID:24464531

Separate and combined impact of acute naltrexone and alprazolam on subjective and physiological effects of oral d-amphetamine in stimulant users.

PubMed

Marks, Katherine R; Lile, Joshua A; Stoops, William W; Rush, Craig R

2014-07-01

Opioid antagonists (e.g., naltrexone) and positive modulators of γ-aminobutyric-acidA (GABAA) receptors (e.g., alprazolam) modestly attenuate the abuse-related effects of stimulants like amphetamine. The use of higher doses to achieve greater efficacy is precluded by side effects. Combining naltrexone and alprazolam might safely maximize efficacy while avoiding the untoward effects of the constituent compounds. The present pilot study tested the hypothesis that acute pretreatment with the combination of naltrexone and alprazolam would not produce clinically problematic physiological effects or negative subjective effects and would reduce the positive subjective effects of d-amphetamine to a greater extent than the constituent drugs alone. Eight nontreatment-seeking, stimulant-using individuals completed an outpatient experiment in which oral d-amphetamine (0, 15, and 30 mg) was administered following acute pretreatment with naltrexone (0 and 50 mg) and alprazolam (0 and 0.5 mg). Subjective effects, psychomotor task performance, and physiological measures were collected. Oral d-amphetamine produced prototypical physiological and stimulant-like positive subjective effects (e.g., VAS ratings of Active/Alert/Energetic, Good Effect, and High). Pretreatment with naltrexone, alprazolam, and their combination did not produce clinically problematic acute physiological effects or negative subjective effects. Naltrexone and alprazolam each significantly attenuated some of the subjective effects of d-amphetamine. The combination attenuated a greater number of subjective effects than the constituent drugs alone. The present results support the continued evaluation of an opioid receptor antagonist combined with a GABAA-positive modulator using more clinically relevant experimental conditions like examining the effect of chronic dosing with these drugs on methamphetamine self-administration.

Effects of Mentha longifolia L. essential oil and nisin alone and in combination on Bacillus cereus and Bacillus subtilis in a food model and bacterial ultrastructural changes.

PubMed

Pajohi, Mohamad Reza; Tajik, Hossein; Farshid, Amir Abbas; Basti, Afshin Akhondzadeh; Hadian, Mojtaba

2011-02-01

In the face of emerging new pathogens and ever-growing health-conscious customers, food preservation technology remains on the top agenda of food industry. This study was aimed at determining the effects of the essential oil of Mentha longifolia L., alone and in combination with nisin, on Bacillus cereus and Bacillus subtilis at 8°C and 25°C in a food model (commercial barley soup) during 15 days. The essential oil alone at 8°C inhibited bacterial growth significantly compared with the control (p < 0.05). However, at 25°C, none of the concentrations of the essential oil alone showed inhibitory effect on bacterial growth. At 8°C, the combination effect of the essential oil and nisin on bacteria was noted at 0.25 μg mL(-1) for nisin and 0.05 μL mL(-1) for the essential oil (p < 0.05). The combination of nisin and the essential oil demonstrated significant inhibitory effects on the vegetative forms of bacteria at 25°C, although it was comparable to that of nisin alone at the same concentrations. Electron microscopy studies revealed a great deal of damage to B. cereus treated with a combination of nisin and the essential oil. However, the combination of nisin with the essential oil led to a complete destruction of cell wall and cytoplasm of vegetative cells of B. subtilis.

Judged effectiveness of threat and coping appraisal anti-speeding messages.

PubMed

Cathcart, Rachel L; Glendon, A Ian

2016-11-01

Using a young driver sample, this experimental study sought to identify which combinations of threat-appraisal (TA) and coping-appraisal (CA) messages derived from protection motivation theory (PMT) participants would judge as most effective for themselves, and for other drivers. The criterion variable was reported intention to drive within a signed speed limit. All possible TA/CA combinations of 18 previously highly-rated anti-speeding messages were presented both simultaneously and sequentially. These represented PMT's three TA components: severity, vulnerability, and rewards, and three CA components: self-efficacy, response efficacy, and response costs. Eighty-eight young drivers (34 males) each rated 54 messages for perceived effectiveness for self and other drivers. Messages derived from the TA severity component were judged the most effective. Response cost messages were most effective for females. Reverse third-person effects were found for both females and males, which suggested that combining TA and CA components may increase the perceived relevance of anti-speeding messages for males. The findings have potential value for creating effective roadside anti-speeding messages, meriting further investigation in field studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using Raman Spectroscopy in Studying the Effect of Propylene Glycol, Oleic Acid, and Their Combination on the Rat Skin.

PubMed

Atef, Eman; Altuwaijri, Njoud

2018-01-01

The permeability enhancement effect of oleic acid (OA) and propylene glycol (PG) as well as their (1:1 v/v) combined mixture was studied using rat skin. The percutaneous drug administration is a challenge and an opportunity for drug delivery. To date, there is limited research that illustrates the mechanism of penetration enhancers and their combinations on the skin. This project aims to explore the skin diffusion and penetration enhancement of PG, OA, and a combination of PG-OA (1:1 v/v) on rat skin and to identify the potential synergistic effect of the two enhancers utilizing Raman spectroscopy. Dissected dorsal skin was treated with either PG or OA or their combination for predetermined time intervals after which the Raman spectra of the treated skin were collected with the enhancer. A spectrum of the wiped and the washed skin were also collected. The skin integrity was tested before and after exposure to PG. The skin histology proved that the skin integrity has been maintained during experiments and the results indicated that OA disrupted rat skin lipid as evident by changes in the lipid peak. The results also showed that PG and OA improved the diffusion of each other and created faster, yet reversible changes of the skin peaks. In conclusion, Raman spectroscopy is a potential tool for ex vivo skin diffusion studies. We also concluded that PG and OA have potential synergistic reversible effect on the skin.

Fluoxetine potentiation of omega-3 fatty acid antidepressant effect: evaluating pharmacokinetic and brain fatty acid-related aspects in rodents.

PubMed

Laino, Carlos Horacio; Garcia, Pilar; Podestá, María Fernanda; Höcht, Christian; Slobodianik, Nora; Reinés, Analía

2014-10-01

We previously reported that combined fluoxetine administration at antidepressant doses renders additive antidepressant effects, whereas non-antidepressant doses potentiate the omega-3 fatty acid antidepressant effect. In the present study, we aimed to evaluate putative pharmacokinetic and brain omega-3 fatty acid-related aspects for fluoxetine potentiation of omega-3 fatty acid antidepressant effect in rats. Coadministration of omega-3 fatty acids with a non-antidepressant dose of fluoxetine (1 mg/kg day) failed to affect both brain fluoxetine concentration and norfluoxetine plasma concentration profile. Fluoxetine plasma concentrations remained below the sensitivity limit of the detection method. Either antidepressant (10 mg/kg day) or non-antidepressant (1 mg/kg day) doses of fluoxetine in combination with omega-3 fatty acids increased hippocampal docosapentaenoic acid (DPA, 22:5 omega-3) levels. Although individual treatments had no effects on DPA concentration, DPA increase was higher when omega-3 were combined with the non-antidepressant dose of fluoxetine. Chronic DPA administration exerted antidepressant-like effects in the forced swimming test while increasing hippocampal docosahexaenoic (22:6 omega-3) and DPA levels. Our results suggest no pharmacokinetic interaction and reveal specific hippocampal DPA changes after fluoxetine and omega-3 combined treatments in our experimental conditions. The DPA role in the synergistic effect of fluoxetine and omega-3 combined treatments will be for sure the focus of future studies. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3316-3325, 2014. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Effects of single pesticides and binary pesticide mixtures on estrone production in H295R cells.

PubMed

Prutner, Wiebke; Nicken, Petra; Haunhorst, Eberhard; Hamscher, Gerd; Steinberg, Pablo

2013-12-01

The aim of the present study was to determine whether the human adrenocortical carcinoma cell line H295R can be used as an in vitro test system to investigate the effects of binary pesticide combinations on estrone production as biological endpoint. In the first step ten pesticides selected according to a tiered approach were tested individually. The anilinopyrimidines cyprodinil and pyrimethanil as well as the dicarboximides iprodione and procymidone increased estrone concentration, while the triazoles myclobutanil and tebuconazole as well as the strobilurins azoxystrobin and kresoxim-methyl decreased estrone concentration in the supernatant of H295R cells. The N-methylcarbamate methomyl did not show any effects, and the phthalimide captan reduced estrone concentration unspecifically due to its detrimental impact on cellular viability. When cyprodinil and pyrimethanil, which belong to the same chemical group and increase estrone production, were combined, in most of the cases the overall effect was solely determined by the most potent compound in the mixture (i.e., cyprodinil). When cyprodinil and procymidone, which belong to different chemical groups but increase estrone production, were combined, in most cases an additive effect was observed. When cyprodinil, which increased estrone production, was combined with either myclobutanil or azoxystrobin, which decreased estrone production, the overall effect of the mixture was in most cases either entirely determined by myclobutanil or at least partially modulated by azoxystrobin. In conclusion, H295R cells appear to be an adequate in vitro test system to study the effect of combining two pesticides affecting estrone production.

[Protective effect of polysaccharides extracts from corn silk against cyclophosphamide induced host damages in mice bearing H22 tumors].

PubMed

Wu, Xian-chuang; Du, Gang-jun; Song, Xiao-yong; Zhang, Yong-zhou; Liu, Yu-xin

2014-10-01

To study the protective effect of polysaccharides from corn silk (PCS) against cyclophosphamide (CTX) induced host damages in mice bearing H22 tumors. The ascitic and solid tumor bearing mice model were established to investigate the anti-tumor effects of different dose of PCS (100, 200 and 300 mg/kg). The effects of PCS alone and with combination of CTX on tumor weight, survival time, thymus and spleen index, white blood cell, nucleated cell of marrow, serum ALT and AST level were tested. The high-dose PCS (300 mg/kg) had significant inhibitory effects on tumor. After combination with CTX, the tumor inhibitory ratio was enhanced to 68.71%, the survival time of tumor-burdened ascites tumor mice was significantly prolonged to 72.07% compared with CTX group. The Q value of combination group was 0.997. Thymus and spleen index, white blood cell, nucleated cell of marrow decreased by CTX were ameliorated significantly. The level of ALT and AST increased by CTX were reduced by combination with PCS. PCS has a potent inhibitory effect on the growth of implanted H22 tumors in mice and has a synergetic effect and an attenuated toxic effect in combination with CTX.

Explanation of non-additive effects in mixtures of similar mode of action chemicals.

PubMed

Kamo, Masashi; Yokomizo, Hiroyuki

2015-09-01

Many models have been developed to predict the combined effect of drugs and chemicals. Most models are classified into two additive models: independent action (IA) and concentration addition (CA). It is generally considered if the modes of action of chemicals are similar then the combined effect obeys CA; however, many empirical studies report nonlinear effects deviating from the predictions by CA. Such deviations are termed synergism and antagonism. Synergism, which leads to a stronger toxicity, requires more careful management, and hence it is important to understand how and which combinations of chemicals lead to synergism. In this paper, three types of chemical reactions are mathematically modeled and the cause of the nonlinear effects among chemicals with similar modes of action was investigated. Our results show that combined effects obey CA only when the modes of action are exactly the same. Contrary to existing knowledge, combined effects are generally nonlinear even if the modes of action of the chemicals are similar. Our results further show that the nonlinear effects vanish out when the chemical concentrations are low, suggesting that the current management procedure of assuming CA is rarely inappropriate because environmental concentrations of chemicals are generally low. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Synergistic effect of the interaction between naproxen and citral on inflammation in rats.

PubMed

Ortiz, Mario I; González-García, Martha P; Ponce-Monter, Héctor A; Castañeda-Hernández, Gilberto; Aguilar-Robles, Paulina

2010-12-15

The combination of non-steroidal anti-inflammatory drugs with herbs having analgesic effects can increase their antinociceptive activity and limit their side effects. The aim of the present study was to examine the effects on inflammation and gastric injury in rats resulting from the interaction between naproxen and citral. Naproxen, citral, or fixed-dose naproxen-citral combinations were administered orally and their anti-inflammation (carrageenan-induced paw edema) and gastric damage were assessed in rats. The pharmacological interaction type was evaluated by the isobolographic analysis. Naproxen, citral, or combinations of naproxen and citral produced anti-inflammatory effects. The sole administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or combinations. ED(30) values were estimated for the individual drugs, and isobolograms were constructed. The derived theoretical ED(30) for the anti-inflammatory effect was 504.4 mg/kg; this was significantly higher than the observed experimental value (190.6 mg/kg). These results indicate that a synergistic interaction underlies the anti-inflammatory effect. The data suggests that the naproxen-citral combination can interact and to produce minor gastric damage and may have therapeutic advantages for the clinical treatment of inflammation. Copyright © 2010 Elsevier GmbH. All rights reserved.

The Effects of Carbohydrates, in Isolation and Combined with Caffeine, on Cognitive Performance and Mood—Current Evidence and Future Directions

PubMed Central

Lawton, Clare Louise

2018-01-01

This review examines the effects of carbohydrates, delivered individually and in combination with caffeine, on a range of cognitive domains and subjective mood. There is evidence for beneficial effects of glucose at a dose of 25 g on episodic memory, but exploration of dose effects has not been systematic and the effects on other cognitive domains is not known. Factors contributing to the differential sensitivity to glucose facilitation include age, task difficulty/demand, task domain, and glucoregulatory control. There is modest evidence to suggest modulating glycemic response may impact cognitive function. The evidence presented in this review identifies dose ranges of glucose and caffeine which improve cognition, but fails to find convincing consistent synergistic effects of combining caffeine and glucose. Whilst combining glucose and caffeine has been shown to facilitate cognitive performance and mood compared to placebo or glucose alone, the relative contribution of caffeine and glucose to the observed effects is difficult to ascertain, due to the paucity of studies that have appropriately compared the effects of these ingredients combined and in isolation. This review identifies a number of methodological challenges which need to be considered in the design of future hypothesis driven research in this area. PMID:29425182

Curcumin Sensitizes Silymarin to Exert Synergistic Anticancer Activity in Colon Cancer Cells.

PubMed

Montgomery, Amanda; Adeyeni, Temitope; San, KayKay; Heuertz, Rita M; Ezekiel, Uthayashanker R

2016-01-01

We studied combinatorial interactions of two phytochemicals, curcumin and silymarin, in their action against cancer cell proliferation. Curcumin is the major component of the spice turmeric. Silymarin is a bioactive component of milk thistle used as a protective supplement against liver disease. We studied antiproliferative effects of curcumin alone, silymarin alone and combinations of curcumin and silymarin using colon cancer cell lines (DLD-1, HCT116, LoVo). Curcumin inhibited colon cancer cell proliferation in a concentration-dependent manner, whereas silymarin showed significant inhibition only at the highest concentrations assessed. We found synergistic effects when colon cancer cells were treated with curcumin and silymarin together. The combination treatment led to inhibition of colon cancer cell proliferation and increased apoptosis compared to single compound treated cells. Combination treated cells exhibited marked cell rounding and membrane blebbing of apoptotic cells. Curcumin treated cells showed 3-fold more caspase3/7 activity whereas combination treated cells showed 5-fold more activity compared to control and silymarin treated cells. When DLD-1 cells were pre-exposed to curcumin, followed by treatment with silymarin, the cells underwent a high amount of cell death. The pre-exposure studies indicated curcumin sensitization of silymarin effect. Our results indicate that combinatorial treatments using phytochemicals are effective against colorectal cancer.

The effects of whole-body vibration in isolation or combined with strength training in female athletes.

PubMed

Preatoni, Ezio; Colombo, Alessandro; Verga, Monica; Galvani, Christel; Faina, Marcello; Rodano, Renato; Preatoni, Ennio; Cardinale, Marco

2012-09-01

The aims of this study were to assess the behavior of a vibrating platform under different conditions and to compare the effects of an 8-week periodized training program with whole-body vibration (WBV) alone or in combination with conventional strength training (ST). Vibrating frequencies, displacements, and peak accelerations were tested through a piezoelectric accelerometer under different conditions of load and subjects' position. Eighteen national-level female athletes were assigned to 1 of 3 different groups performing WBV, conventional ST, or a combination of the 2 (WBV + ST). Isometric maximal voluntary contraction, dynamic maximal concentric force, and vertical jump tests were performed before and after the conditioning program. Vibrating displacements and maximum accelerations measured on the device were not always consistent with their expected values calculated from the display and manufacturers' information (sinusoidal waveforms). The WBV alone or in combination with low-intensity resistance exercise did not seem to induce significant enhancements in force and power when compared with ST. It appears that WBV cannot substitute parts of ST loading in a cohort of young female athletes. However, vibration effects might be limited by the behavior of the commercial platforms as the one used in the study. More studies are needed to analyze the performances of devices and the effectiveness of protocols.

Effective techniques in healthy eating and physical activity interventions: a meta-regression.

PubMed

Michie, Susan; Abraham, Charles; Whittington, Craig; McAteer, John; Gupta, Sunjai

2009-11-01

Meta-analyses of behavior change (BC) interventions typically find large heterogeneity in effectiveness and small effects. This study aimed to assess the effectiveness of active BC interventions designed to promote physical activity and healthy eating and investigate whether theoretically specified BC techniques improve outcome. Interventions, evaluated in experimental or quasi-experimental studies, using behavioral and/or cognitive techniques to increase physical activity and healthy eating in adults, were systematically reviewed. Intervention content was reliably classified into 26 BC techniques and the effects of individual techniques, and of a theoretically derived combination of self-regulation techniques, were assessed using meta-regression. Valid outcomes of physical activity and healthy eating. The 122 evaluations (N = 44,747) produced an overall pooled effect size of 0.31 (95% confidence interval = 0.26 to 0.36, I(2) = 69%). The technique, "self-monitoring," explained the greatest amount of among-study heterogeneity (13%). Interventions that combined self-monitoring with at least one other technique derived from control theory were significantly more effective than the other interventions (0.42 vs. 0.26). Classifying interventions according to component techniques and theoretically derived technique combinations and conducting meta-regression enabled identification of effective components of interventions designed to increase physical activity and healthy eating. PsycINFO Database Record (c) 2009 APA, all rights reserved.

Cost-Effectiveness of Non-Invasive and Non-Pharmacological Interventions for Low Back Pain: a Systematic Literature Review.

PubMed

Andronis, Lazaros; Kinghorn, Philip; Qiao, Suyin; Whitehurst, David G T; Durrell, Susie; McLeod, Hugh

2017-04-01

Low back pain (LBP) is a major health problem, having a substantial effect on peoples' quality of life and placing a significant economic burden on healthcare systems and, more broadly, societies. Many interventions to alleviate LBP are available but their cost effectiveness is unclear. To identify, document and appraise studies reporting on the cost effectiveness of non-invasive and non-pharmacological treatment options for LBP. Relevant studies were identified through systematic searches in bibliographic databases (EMBASE, MEDLINE, PsycINFO, Cochrane Library, CINAHL and the National Health Service Economic Evaluation Database), 'similar article' searches and reference list scanning. Study selection was carried out by three assessors, independently. Study quality was assessed using the Consensus on Health Economic Criteria checklist. Data were extracted using customized extraction forms. Thirty-three studies were identified. Study interventions were categorised as: (1) combined physical exercise and psychological therapy, (2) physical exercise therapy only, (3) information and education, and (4) manual therapy. Interventions assessed within each category varied in terms of their components and delivery. In general, combined physical and psychological treatments, information and education interventions, and manual therapies appeared to be cost effective when compared with the study-specific comparators. There is inconsistent evidence around the cost effectiveness of physical exercise programmes as a whole, with yoga, but not group exercise, being cost effective. The identified evidence suggests that combined physical and psychological treatments, medical yoga, information and education programmes, spinal manipulation and acupuncture are likely to be cost-effective options for LBP.

Effectiveness of a Combined Tutoring and Mentoring Intervention with Ninth-Grade, Urban Black Adolescents

ERIC Educational Resources Information Center

Somers, Cheryl L.; Wang, Dan; Piliawsky, Monte

2016-01-01

This quasi-experimental study examined the effectiveness of a combined tutoring and mentoring intervention for urban, low-income Black youth during the transition to high school. Participants were 118 ninth-grade students (experimental n = 69; comparison n = 49). After 7 months in the intervention program, students in the experimental group showed…

Effect of combined folic acid, Vitamin B6, and Vitamin B12 on colorectal adenoma

USDA-ARS?s Scientific Manuscript database

Folic acid, vitamin B(6), and vitamin B(12) act in concert in the one-carbon metabolism and may protect against colorectal neoplasia. We examined the effect of combined B-vitamin treatment on the occurrence of colorectal adenoma. The Women's Antioxidant and Folic Acid Cardiovascular Study was a rand...

Combining Multilevel Analysis with National Value-Added Data Sets - A Case Study to Explore the Effects of School Diversity

ERIC Educational Resources Information Center

Schagen, Ian; Schagen, Sandie

2005-01-01

The advent of large-scale matched data sets, linking pupils' attainment across key stages, gives new opportunities to explore the effects of school organisational factors on pupil performance. Combined with currently available sophisticated and efficient software for multilevel analysis, it offers educational researchers the chance to develop…

The Effects of a Combined Academic and Personal Counselling Initiative for Post-Secondary Student Retention

ERIC Educational Resources Information Center

Bilodeau, Cynthia; Meissner, John

2018-01-01

This study investigated the effectiveness of a combined academic and personal counselling initiative on student performance and emotional well-being outcomes of 289 at-risk students at a Canadian University. Criterion for risk included academic struggles, mental health distress, or both. The program was developed to be tailored to individual…

Effects of Crowding Combined with Mood on Working Memory Performance among College Students

ERIC Educational Resources Information Center

Daniel, Lisa

2012-01-01

This study investigated the effects of crowding combined with mood on working memory performance among college students. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web…

Effects of dietary mixture of garlic (Allium sativum), coriander (Coriandrum sativum) and probiotics on immune responses and caecal counts in young laying hens.

PubMed

Lee, J S; Kim, M J; Park, S H; Lee, S B; Wang, T; Jung, U S; Im, J; Kim, E J; Lee, K W; Lee, H G

2017-10-01

This study was conducted to evaluate the effects of a combined mixture of phytogenic extracts (garlic and coriander) and probiotics on growth performance and immune responses in laying hens based on the results of in vitro studies to screen for immunomodulatory potency of each ingredient. Several parameters of immunomodulatory potency were estimated using lamina propria leucocytes (LPLs) isolated from rat intestinal mucosa tissue. Results show that the combined mixture enhanced LPLs proliferation, increased LPL-mediated cytotoxicity against YAC-1 tumour cells, and decreased lipopolysaccharide (LPS)-induced cytokine production including tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in LPLs. For in vivo study, laying hens (n = 50/each diet group) were fed with control diet, a diet containing antibiotics (0.01% per kg feed) or the combined mixture (0.02% per kg feed) for 21 days. The dietary combined mixture improved egg production (p < 0.05) but not growth performance and carcass traits. Interestingly, the patterns of suppressing plasma IFN-γ productions during inflammation by LPS injection and decreasing caecal E. coli counts in the combined mixture group were comparable to those in the antibiotics group. Taken together, our results suggested that the 0.02% of combined mixture of phytogenic extracts and probiotics as ingredients has potential immunomodulatory effects in laying hens. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison.

PubMed

El-Domyati, Moetaz; Abdel-Wahab, Hossam; Hossam, Aliaa

2018-02-01

Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities. This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring. Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation. Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers. Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only. © 2017 Wiley Periodicals, Inc.

Synergistic combination of fluoro chalcone and doxorubicin on HeLa cervical cancer cells by inducing apoptosis

NASA Astrophysics Data System (ADS)

Arianingrum, Retno; Arty, Indyah Sulistyo; Atun, Sri

2017-03-01

Doxorubicin (Dox), a primary chemotherapeutic agent used for cancer treatment is known to have various side effect included multidrug resistance (MDR) phenomenon. Combination chemotherapy is one of some approaches to reduce Dox side effect. Chalcones have been reported to reduce the proliferation of many cancer cells. The research were conducted to investigate the cytotoxic activity and apoptosis induction of a chalcone derivate which is containing fluoro substituent [1 - (4" - fluorophenyl) -3 - (4' - hydroxy - 3' - methoxyphenyl) - 2 - propene - 1 -on] (FHM) and its combination with Dox on HeLa cells line. The observation of the cytotoxic activity was conducted using MTT [3 - (4, 5 - dimethyl thiazol - 2 - y1) - 2.5 - diphenyltetrazolium bromide] assay. Apoptosis induction was determined by flow cytometric. The changes of cell morphology were observed using phase contrast microscopy. The combination index (CI) was used to determine the effect of the combination. The study showed that FHM inhibited the HeLa cell growth with IC50 of 34 μM, while the IC50 of Dox was 1 μM. The combination had a higher inhibitory effect on cell growth compare to the single treatment of FHM and Dox. All of the combination doses under IC50 of FHM and Dox gave synergistic (CI: - 0.7) up to strong synergistic effect (CI: 0.l - 0.3). The synergistic effects of the combination were due to their ability to induce apoptosis in the HeLa cells. According to the result, FHM was potential to be developed as a co-chemotherapeutic agent with Dox for cervical cancer.

The efficiency of combined coagulant and ballast to remove harmful cyanobacterial blooms in a tropical shallow system.

PubMed

Miranda, Marcela; Noyma, Natália; Pacheco, Felipe S; de Magalhães, Leonardo; Pinto, Ernani; Santos, Suzan; Soares, Maria Fernanda A; Huszar, Vera L; Lürling, Miquel; Marinho, Marcelo M

2017-05-01

We tested the hypothesis that a combination of coagulant and ballast could be efficient for removal of positively buoyant harmful cyanobacteria in shallow tropical waterbodies, and will not promote the release of cyanotoxins. This laboratory study examined the efficacy of coagulants [polyaluminium chloride (PAC) and chitosan (made of shrimp shells)] alone, and combined with ballast (lanthanum modified bentonite, red soil or gravel) to remove the natural populations of cyanobacteria collected from a shallow eutrophic urban reservoir with alternating blooms of Cylindrospermopsis and Microcystis. PAC combined with ballast was effective in settling blooms dominated by Microcystis or Cylindrospermopsis. Contrary to our expectation, chitosan combined with ballast was only effective in settling Cylindrospermopsis-dominated blooms at low pH, whereas at pH≥8 no effective flocculation and settling could be evoked. Chitosan also had a detrimental effect on Cylindrospermopsis causing the release of saxitoxins. In contrast, no detrimental effect on Microcystis was observed and all coagulant-ballast treatments were effective in not only settling the Microcystis dominated bloom, but also lowering dissolved microcystin concentrations. Our data show that the best procedure for biomass reduction also depends on the dominant species. Copyright © 2017 Elsevier B.V. All rights reserved.

A clinical pharmacological assessment of doxazosin and enalapril in combination.

PubMed

Bainbridge, A D; Meredith, P A; Elliott, H L

1993-12-01

This study in 12 normotensive males investigated potential pharmacokinetic and pharmacodynamic interaction mechanisms resulting from the combination of enalapril and doxazosin. Blood pressure reductions were consistently greater with the combination but there was no evidence of a significant pharmacodynamic interaction (as determined by heart rate changes, renal function tests or by pressor responsiveness indices) and there was no evidence of a pharmacokinetic interaction with either drug. Responsiveness to each drug i.e. blood pressure reduction per unit drug concentration was not significantly altered in the combination regimen. In conclusion, these results suggest that the combination of enalapril and doxazosin produces a usefully additive hypotensive effect but there was no evidence of synergism i.e an effect which was more than additive.

Probiotics are a good choice in remission of inflammatory bowel diseases: A meta analysis and systematic review.

PubMed

Ganji-Arjenaki, Mahboube; Rafieian-Kopaei, Mahmoud

2018-03-01

Altered gut bacteria and bacterial metabolic pathways are two important factors in initiation and progression of inflammatory bowel disease (IBD). However, efficacy of probiotics in remission of patients with IBD has not been characterized. This study was performed on the studies that specifically assessed the efficacy of probiotics in attaining clinical response on patients with various types of IBD. The efficacy of variant species of probiotics in different conditions and the influence of study quality in outcomes of randomized controlled trials (RCTs) were also assessed. The RCTs were collected by searching in MEDLINE Web of Science and Google scholar. Then all studies were abstracted in abstraction form and the outcomes were analyzed with fixed-effect and mixed-effect models for assessment of efficacy of variant species of probiotics in subgroups of IBDs. Analysis of 9 trials showed that probiotics had not significant effect on Crohn's disease (CD) (p = 0.07) but analysis of 3 trials in children with IBD revealed a significant advantage (p < 0.01). Analysis of 18 trials revealed that probiotics in patients with Ulcerative colitis (UC) in different conditions have significant effects (p = 0.007). VSL#3 probiotics in patients with UC had significant effect (p < 0.01). Combination of Lactobacillus probiotic, prebiotics had significant effect (p = 0.03) only in patients with UC. Combination of Saccharomyces boulardii, Lactobacillus, and VSL#3 probiotics in CD had also a trend for efficiency (p = 0.057). In children with IBD, the combination of Lactobacillus with VSL#3 probiotics had significant effect (p < 0.01). Probiotics are beneficial in IBD, especially the combination ones in UC. © 2017 Wiley Periodicals, Inc.

Combination studies of platinum(II)-based metallointercalators with buthionine-S,R-sulfoximine, 3-bromopyruvate, cisplatin or carboplatin.

PubMed

Garbutcheon-Singh, K Benjamin; Harper, Benjamin W J; Myers, Simon; Aldrich-Wright, Janice R

2014-01-01

With current chemotherapeutic treatment regimes often limited by adverse side effects, the synergistic combination of complexes with anticancer activity appears to offer a promising strategy for effective cancer treatment. This work investigates the anti-proliferative activity using a combination therapy approach where metallointercalators of the type [Pt(IL)(AL)](2+) (where IL is the intercalating ligand and AL is the ancillary ligand) are used in combination with currently approved anticancer drugs cisplatin and carboplatin and organic molecules buthionine-S,R-sulfoximine and 3-bromopyruvate. Synergistic relationships were observed, indicating a potential to decrease dose-dependent toxicity and improve therapeutic efficacy.

New clinical trial studies drug combination for recurring ovarian cancer | Center for Cancer Research

Cancer.gov

A new clinical trial is studying the effectiveness of an investigational drug combination that looks to see whether reducing the supply of oxygen to the cancer cells can make ovarian cancer shrink or slow its growth in association with an enzyme that repairs DNA damage.

A novel resveratrol-salinomycin combination sensitizes ER-positive breast cancer cells to apoptosis.

PubMed

Venkatadri, Rajkumar; Iyer, Anand Krishnan V; Kaushik, Vivek; Azad, Neelam

2017-08-01

Resveratrol is a dietary compound that has been widely reported for its anticancer activities. However, successful extrapolation of its effects to pre-clinical studies is met with limited success due to inadequate bioavailability. We investigated the potential of combination therapy to improve the efficacy of resveratrol in a more physiologically relevant dose range. The effect of resveratrol on canonical Wnt signaling was evaluated by Western blotting. Wnt modulators HLY78 (activator) and salinomycin (inhibitor) were evaluated in combination with resveratrol for their effect on breast cancer cell viability (MTT assay), cell cycle progression and apoptosis (Western blotting). Bliss independency model was used to evaluate combinatorial effects of resveratrol-salinomycin combination. Resveratrol downregulated canonical Wnt signaling proteins in treated breast cancer cells (MCF-7, MDA-MB-231 and MDA-MB-468) in the dose range of 50-200μM, which also affected cellular viability. However, at very low doses (0-50μM), resveratrol exhibited no cellular toxicity. Co-treatment with salinomycin significantly potentiated the anti-cancer effects of resveratrol, whereas HLY78 co-treatment had minimal effect. Bliss independency model revealed that Wnt inhibition synergistically potentiates the effects of resveratrol in MCF-7 and BT474 cells. Significantly downregulated canonical Wnt signaling proteins and marker of epithelial-mesenchymal transition (EMT), vimentin were observed in cells treated with resveratrol-salinomycin combination. Cell cycle arrest, caspase activation and apoptosis induction in cells treated with resveratrol-salinomycin combination further confirmed the efficacy of the combination. We report a novel resveratrol-salinomycin combination for targeting ER-positive breast cancer cells and present evidence for successful pre-clinical implementation of resveratrol. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo.

PubMed

Meng, Jieru; Dai, Bingbing; Fang, Bingliang; Bekele, B Nebiyou; Bornmann, William G; Sun, Duoli; Peng, Zhenghong; Herbst, Roy S; Papadimitrakopoulou, Vassiliki; Minna, John D; Peyton, Michael; Roth, Jack A

2010-11-29

AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. The efficacy of this combination in lung cancer is unknown. Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. Thus we hypothesized that dual inhibition of both downstream MEK and AKT pathways would induce synergistic antitumor activity. In this study, we evaluated the efficacy of AZD6244 and MK2206 individually on a large panel of lung cancer cell lines. Then, we treated 28 human lung cancer cell lines with a combination of AZD6244 and MK2206 at clinically applicable drug molar ratios. The AZD6244-MK2206 combination therapy resulted in a synergistic effect on inhibition of lung cancer cell growth compared to the results of single drug treatment alone. MK2206 enhanced AZD6244-induced Bim overexpression and apoptosis in A549 and H157 cells. When we tested the combination of AZD6244 and MK2206 at ratios of 8∶1, 4∶1, 2∶1, and 1∶8, we found that the synergistic effect of the combination therapy was ratio-dependent. At ratios of 8∶1, 4∶1, and 2∶1, the drug combination consistently demonstrated synergy, whereas decreasing the ratio to 1∶8 resulted in a loss of synergy and produced an additive or antagonistic effect in most cell lines. Furthermore, the AZD6244-MK2206 combination therapy showed synergy in the suppression of A549 and H157 xenograft tumor growth and increased mean animal survival time. The AZD6244-MK2206 combination therapy resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. In addition, a significant increase of apoptosis was detected in tumor tissue from mice treated with AZD6244-MK2206 compared with that from the single agent treated mice. Our study suggests that the combination of AZD6244 and MK2206 has a significant synergistic effect on tumor growth in vitro and in vivo and leads to increased survival rates in mice bearing highly aggressive human lung tumors.

Supplementation with Brazil nuts and green tea extract regulates targeted biomarkers related to colorectal cancer risk in humans.

PubMed

Hu, Ying; McIntosh, Graeme H; Le Leu, Richard K; Somashekar, Roshini; Meng, Xing Q; Gopalsamy, Geetha; Bambaca, Libby; McKinnon, Ross A; Young, Graeme P

2016-12-01

Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers. In total, thirty-two volunteers (>50 years of age) with plasma Se≤1·36 µmol/l were randomised to one of three treatment groups: nine to Se (approximately 48 µg/d) as six Brazil nuts, eleven to four GTE capsules (800 mg (-)-epigallocatechin-3-gallate) and twelve to a combination of Brazil nuts and GTE. Blood and rectal biopsies were obtained before and after each intervention. Plasma Se levels, rectal selenoprotein P (SePP) and β-catenin mRNA increased significantly in subjects consuming Brazil nuts alone or in combination, whereas rectal DNA methyltransferase (DNMT1) and NF-κB mRNA were reduced significantly in subjects consuming GTE alone or in combination. None of the interventions significantly affected rectal acetylated histone H3 or Ki-67 expression at the protein level or plasma C-reactive protein. Effects of the combination of Brazil nuts and GTE did not differ from what would be expected from either agent alone. In conclusion, supplementation of Brazil nuts and/or GTE regulates targeted biomarkers related to CRC oncogenesis, specifically genes associated with selenoproteins (SePP), WNT signalling (β-catenin), inflammation (NF-κB) and methylation (DNMT1). Their combination does not appear to provide additional effects compared with either agent alone.

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors.

PubMed

Grenier, Jeremy M; Yeung, Stephen T; Qiu, Zhijuan; Jellison, Evan R; Khanna, Kamal M

2017-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1 b , on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1 b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection.

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors

PubMed Central

Grenier, Jeremy M.; Yeung, Stephen T.; Qiu, Zhijuan; Jellison, Evan R.; Khanna, Kamal M.

2018-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1b, on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection. PMID:29387061

A review of the combination among global change factors in forests, shrublands and pastures of the Mediterranean Region: Beyond drought effects

NASA Astrophysics Data System (ADS)

Doblas-Miranda, E.; Alonso, R.; Arnan, X.; Bermejo, V.; Brotons, L.; de las Heras, J.; Estiarte, M.; Hódar, J. A.; Llorens, P.; Lloret, F.; López-Serrano, F. R.; Martínez-Vilalta, J.; Moya, D.; Peñuelas, J.; Pino, J.; Rodrigo, A.; Roura-Pascual, N.; Valladares, F.; Vilà, M.; Zamora, R.; Retana, J.

2017-01-01

Climate change, alteration of atmospheric composition, land abandonment in some areas and land use intensification in others, wildfires and biological invasions threaten forests, shrublands and pastures all over the world. However, the impacts of the combinations between global change factors are not well understood despite its pressing importance. Here we posit that reviewing global change factors combination in an exemplary region can highlight the necessary aspects in order to better understand the challenges we face, warning about the consequences, and showing the challenges ahead of us. The forests, shrublands and pastures of the Mediterranean Basin are an ideal scenario for the study of these combinations due to its spatial and temporal heterogeneity, increasing and diverse human population and the historical legacy of land use transformations. The combination of multiple global change factors in the Basin shows different ecological effects. Some interactions alter the effects of a single factor, as drought enhances or decreases the effects of atmospheric components on plant ecophysiology. Several interactions generate new impacts: drought and land use changes, among others, alter water resources and lead to land degradation, vegetation regeneration decline, and expansion of forest diseases. Finally, different factors can occur alone or simultaneously leading to further increases in the risk of fires and biological invasions. The transitional nature of the Basin between temperate and arid climates involves a risk of irreversible ecosystem change towards more arid states. However, combinations between factors lead to unpredictable ecosystem alteration that goes beyond the particular consequences of drought. Complex global change scenarios should be studied in the Mediterranean and other regions of the world, including interregional studies. Here we show the inherent uncertainty of this complexity, which should be included in any management strategy.

Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

PubMed

Lima, Glaura C; Silva, Emilia V; Magalhães, Pérola de O; Naves, Janeth S

Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance. To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis. A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment. The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Combined exposure to protons and 56Fe leads to overexpression of Il13 and reactivation of repetitive elements in the mouse lung

NASA Astrophysics Data System (ADS)

Nzabarushimana, Etienne; Prior, Sara; Miousse, Isabelle R.; Pathak, Rupak; Allen, Antiño R.; Latendresse, John; Olsen, Reid H. J.; Raber, Jacob; Hauer-Jensen, Martin; Nelson, Gregory A.; Koturbash, Igor

2015-11-01

Interest in deep space exploration underlines the needs to investigate the effects of exposure to combined sources of space radiation. The lung is a target organ for radiation, and exposure to protons and heavy ions as radiation sources may lead to the development of degenerative disease and cancer. In this study, we evaluated the pro-fibrotic and epigenetic effects of exposure to protons (150 MeV/nucleon, 0.1 Gy) and heavy iron ions (56Fe, 600 MeV/nucleon, 0.5 Gy) alone or in combination (protons on Day 1 and 56Fe on Day 2) in C57BL/6 male mice 4 weeks after irradiation. Exposure to 56Fe, proton or in combination, did not result in histopathological changes in the murine lung. At the same time, combined exposure to protons and 56Fe resulted in pronounced molecular alterations in comparison with either source of radiation alone. Specifically, we observed a substantial increase in the expression of cytokine Il13, loss of expression of DNA methyltransferase Dnmt1, and reactivation of LINE-1, SINE B1 retrotransposons, and major and minor satellites. Given the deleterious potential of the observed effects that may lead to development of chronic lung injury, pulmonary fibrosis, and cancer, future studies devoted to the investigation of the long-term effects of combined exposures to proton and heavy ions are clearly needed.

Combined exposure to protons and 56Fe leads to overexpression of Il13 and reactivation of repetitive elements in the mouse lung

PubMed Central

Nzabarushimana, Etienne; Prior, Sara; Miousse, Isabelle R.; Pathak, Rupak; Allen, Antino R.; Latendresse, John; Olsen, Reid H.J.; Raber, Jacob; Hauer-Jensen, Martin; Nelson, Gregory A.; Koturbash, Igor

2015-01-01

Interest in deep space exploration underlines the needs to investigate the effects of exposure to combined sources of space radiation. The lung is a target organ for radiation, and exposure to protons and heavy ions as radiation sources may lead to the development of degenerative disease and cancer. In this study, we evaluated the pro-fibrotic and epigenetic effects of exposure to protons (150 MeV/nucleon, 0.1 Gy) and heavy iron ions (56Fe, 600 MeV/nucleon, 0.5 Gy) alone or in combination (protons on Day 1 and 56Fe on Day 2) in C57BL/6 male mice 4 weeks after irradiation). Exposure to 56Fe, proton or in combination, did not result in histopathological changes in the murine lung. At the same time, combined exposure to protons and 56Fe resulted in pronounced molecular alterations in comparison with either source of radiation alone. Specifically, we observed a substantial increase in the expression of cytokine Il13, loss of expression of DNA methyltransferase Dnmt1, and reactivation of LINE-1, SINE B1 retrotransposons, and major and minor satellites. Given the deleterious potential of the observed effects that may lead to development of chronic lung injury, pulmonary fibrosis, and cancer, future studies devoted to the investigation of the long-term effects of combined exposures to proton and heavy ions are clearly needed. PMID:26553631

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

PubMed

Abdel-Kader, Maged S; Abulhamd, Ashraf T; Hamad, Abubaker M; Alanazi, Abdullah H; Ali, Rizwan; Alqasoumi, Saleh I

2018-05-01

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in  Glycyrrhiza glabra  (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Chen, Yunbo; Zhang, Guijuan; Chen, Xiaoping; Jiang, Xuefeng; Yuan, Naijun; Wang, Yurong; Hao, Xiaoqian

2018-01-01

Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment. PMID:29675052

Which Treatment is More Effective for Functional Ankle Instability: Strengthening or Combined Muscle Strengthening and Proprioceptive Exercises?

PubMed

Kim, Ki-Jong; Kim, Young-Eok; Jun, Hyun-Ju; Lee, Jin-Su; Ji, Sung-Ha; Ji, Sang-Goo; Seo, Tae-Hwa; Kim, Young-Ok

2014-03-01

[Purpose] The purpose of this study was to implement combined muscle strengthening and proprioceptive exercises to examine the effects of combined exercises on functional ankle instability. [Subjects and Methods] Experiments were conducted with 30 adult males and females. The study subjects were randomly assigned to either a control group (Group A), a muscle strengthening exercise group (Group B), or a combined muscle strengthening and proprioceptive exercise group (Group C) consisting of 10 subjects each. In Group A, measurements were only conducted before and after the experiment without any intervention, whereas the exercise programs for Group B and Group C were implemented three days per week for four weeks. [Results] Muscle strength showed significant increases in Groups B and C compared with the control group during plantar flexion, dorsiflexion, inversion, and eversion. The Cumberland ankle instability tool showed significant increases in Group B and Group C compared with Group A and significant increases in Group C compared with Group B. [Conclusion] Applying combined muscle strengthening and proprioceptive exercises to those who have functional ankle instability is more effective than applying only muscle strengthening exercises.

Anticonvulsant and psychomotor activity of nitrendipine alone and in combination with phenytoin and valproate in rats.

PubMed

Balakrishnan, S; Bhargava, V K; Pandhi, P

1999-01-01

The effect of nitrendipine (NTP) alone and in combination with phenytoin (PHT) and valproate (VPA) against maximal electroshock seizures (MES) was studied in rats. In addition, the psychomotor effects of NTP alone and in combination with PHT and VPA were evaluated using the following tests: a) rotarod performance; b) spontaneous motor activity; c) despair behavior; d) righting reflex; e) hole board test; and f) passive avoidance test. ED50 values of PHT, VPA and NTP were 13,255 and 3.6 mg/kg, respectively. When NTP was combined with PHT or VPA, the ED50 values decreased to 0.9 and 226 mg/kg, respectively. In the psychomotor function tests, for the same degree of protection (50%) afforded against MES, PHT or VPA produced a greater impairment in all the parameters compared to NTP alone or a combination of NTP with PHT or VPA. Furthermore, NTP reversed the depression and long-term memory loss induced by PHT and VPA. Thus, NTP was effective against MES in rats, potentiating the anti-electroshock activity of PHT and VPA and producing less impairment of psychomotor activity. Thus, the agent can be considered a potential antiepileptic warranting further studies.

Effect of combined oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models.

PubMed

Rock, Erin M; Connolly, Cassidy; Limebeer, Cheryl L; Parker, Linda A

2016-09-01

The purpose of this study was to evaluate the potential of oral combined cannabis constituents to reduce nausea. The objective of this study was to determine the effect of combining subthreshold oral doses of Δ(9)-tetrahydrocannabinol (THC) and cannabidiolic acid (CBDA) on acute and anticipatory nausea in rat models of conditioned gaping. The potential of intragastric (i.g.) administration of THC, CBDA, or combined doses, to interfere with acute nausea-induced conditioned gaping (acute nausea) or the expression of contextually elicited conditioned gaping (anticipatory nausea), was evaluated. For acute nausea, i.g. administration of subthreshold doses of THC (0.5 and 1 mg/kg) or CBDA (0.5 and 1 μg/kg) significantly suppressed acute nausea-induced gaping, whereas higher individual doses of both THC and CBDA were maximally effective. Combined i.g. administration of higher doses of THC and CBDA (2.5 mg/kg THC-2.5 μg/kg CBDA; 10 mg/kg THC-10 μg/kg CBDA; 20 mg/kg THC-20 μg/kg CBDA) also enhanced positive hedonic reactions elicited by saccharin solution during conditioning. For anticipatory nausea, combined subthreshold i.g. doses of THC (0.1 mg/kg) and CBDA (0.1 μg/kg) suppressed contextually elicited conditioned gaping. When administered i.g., THC was effective on its own at doses ranging from 1 to 10 mg/kg, but CBDA was only effective at 10 μg/kg. THC alone was equally effective by intraperitoneal (i.p.) and i.g. administration, whereas CBDA alone was more effective by i.p. administration (Rock et al. in Psychopharmacol (Berl) 232:4445-4454, 2015) than by i.g. administration. Oral administration of subthreshold doses of THC and CBDA may be an effective new treatment for acute nausea and anticipatory nausea and appetite enhancement in chemotherapy patients.

The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model.

PubMed

Feng, Jiuhuan; Qin, Shukui

2018-01-01

Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib mono-therapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib. We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased. The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time. The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment.

The synergistic effects of Apatinib combined with cytotoxic chemotherapeutic agents on gastric cancer cells and in a fluorescence imaging gastric cancer xenograft model

PubMed Central

Feng, Jiuhuan; Qin, Shukui

2018-01-01

Introduction Methylsulfonic apatinib (hereinafter referred to as Apatinib) is a small-molecule angiogenesis inhibitor highly and selectively targeted to vascular endothelial growth factor receptor-2. At present, a series of basic and clinical studies have confirmed that Apatinib mono-therapy can inhibit the growth of different carcinomas. Our experiment aimed to determine whether there is a synergistic effect between the combination of the traditional cytotoxic chemotherapy drugs paclitaxel (TAX), oxaliplatin (L-OHP), 5-fluorouracil (5-FU), and Apatinib. Materials and methods We evaluated the combined effect using cytological experiments and a fluorescence imaging xenograft model. In vitro, the inhibition of cell proliferation increased notably when Apatinib was combined with TAX, L-OHP, and 5-FU. Then, for the mechanistic research, we selected the optimal dose of drugs that also had a synergistic effect. Apatinib combined with the aforementioned drugs, especially the combination of Apatinib and 5-FU, decreased the invasion and migration ability of the cells and increased the apoptosis ratio; expression of the anti-apoptotic protein Bcl-2 significantly decreased, and expression of the pro-apoptotic protein Bax increased. In vivo, when Apatinib was combined with TAX, L-OHP, and 5-FU, the volume of the xenograft model was significantly inhibited, the strength of the green fluorescence was weakened and the microvessel density decreased. Results The combination of Apatinib with TAX and 5-FU was synergistic (coefficient of drug interaction <1); the combination effect of Apatinib and L-OHP was only additive, with a shorter associated survival time. Conclusion The combination of Apatinib and classical chemotherapy drugs may be an optimal choice for gastric cancer treatment. PMID:29872316

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

PubMed

El-Hamamsy, Manal H; Elsisi, Gihan H; Eldessouki, Randa; Elmazar, Mohamed M; Taha, Ahmed S; Awad, Basma F; Elmansy, Hossam

2016-08-01

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014. The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.

Evaluation of synergistic antioxidant potential of complex mixtures using oxygen radical absorbance capacity (ORAC) and electron paramagnetic resonance (EPR).

PubMed

Parker, Tory L; Miller, Samantha A; Myers, Lauren E; Miguez, Fernando E; Engeseth, Nicki J

2010-01-13

Previous research has demonstrated that certain combinations of compounds result in a decrease in toxic or pro-oxidative effects, previously noted when compounds were administered singly. Thus, there is a need to study many complex interactions further. Two in vitro techniques [electron paramagnetic resonance (EPR) and oxygen radical absorbance capacity (ORAC) assays] were used in this study to assess pro- and antioxidant capacity and synergistic potential of various compounds. Rutin, p-coumaric acid, abscisic acid, ascorbic acid, and a sugar solution were evaluated individually at various concentrations and in all 26 possible combinations at concentrations found in certain foods (honey or papaya), both before and after simulated digestion. EPR results indicated sugar-containing combinations provided significantly higher antioxidant capacity; those combinations containing sugars and ascorbic acid demonstrated synergistic potential. The ORAC assay suggested additive effects, with some combinations having synergistic potential, although fewer combinations were significantly synergistic after digestion. Finally, ascorbic acid, caffeic acid, quercetin, and urate were evaluated at serum-achievable levels. EPR analysis did not demonstrate additive or synergistic potential, although ORAC analysis did, principally in combinations containing ascorbic acid.

Individual patient data meta-analysis of combined treatments versus psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for adult depression: a protocol.

PubMed

Weitz, Erica; Kleiboer, Annet; van Straten, Annemieke; Hollon, Steven D; Cuijpers, Pim

2017-02-13

There are many proven treatments (psychotherapy, pharmacotherapy or their combination) for the treatment of depression. Although there is growing evidence for the effectiveness of combination treatment (psychotherapy + pharmacotherapy) over pharmacotherapy alone, psychotherapy alone or psychotherapy plus pill placebo, for depression, little is known about which specific groups of patients may respond best to combined treatment versus monotherapy. Conventional meta-analyses techniques have limitations when tasked with examining whether specific individual characteristics moderate the effect of treatment on depression. Therefore, this protocol outlines an individual patient data (IPD) meta-analysis to explore which patients, with which clinical characteristics, have better outcomes in combined treatment compared with psychotherapy (alone or with pill placebo), pharmacotherapy and pill placebo. Study searches are completed using an established database of randomised controlled trials (RCTs) on the psychological treatment of adult depression that has previously been reported. Searches were conducted in PubMed, PsycInfo, Embase and the Cochrane Central Register of Controlled Trials. RCTs comparing combination treatment (psychotherapy + pharmacotherapy) with psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for the treatment of adult depression will be included. Study authors of eligible trials will be contacted and asked to contribute IPD. Conventional meta-analysis techniques will be used to examine differences between studies that have contributed data and those that did not. Then, IPD will be harmonised and analysis using multilevel regression will be conducted to examine effect moderators of treatment outcomes. Study results outlined above will be published in peer-reviewed journals. Study results will contribute to better understanding whether certain patients respond best to combined treatment or other depression treatments and provide new information on moderators of treatment outcome that can be used by patients, clinicians and researchers. CRD42016039028. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Meta-Analysis of Effect Sizes Reported at Multiple Time Points Using General Linear Mixed Model.

PubMed

Musekiwa, Alfred; Manda, Samuel O M; Mwambi, Henry G; Chen, Ding-Geng

2016-01-01

Meta-analysis of longitudinal studies combines effect sizes measured at pre-determined time points. The most common approach involves performing separate univariate meta-analyses at individual time points. This simplistic approach ignores dependence between longitudinal effect sizes, which might result in less precise parameter estimates. In this paper, we show how to conduct a meta-analysis of longitudinal effect sizes where we contrast different covariance structures for dependence between effect sizes, both within and between studies. We propose new combinations of covariance structures for the dependence between effect size and utilize a practical example involving meta-analysis of 17 trials comparing postoperative treatments for a type of cancer, where survival is measured at 6, 12, 18 and 24 months post randomization. Although the results from this particular data set show the benefit of accounting for within-study serial correlation between effect sizes, simulations are required to confirm these results.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

Effects of vinpocetine and ozagrel on behavioral recovery of rats after global brain ischemia.

PubMed

Jincai, Wang; Tingfang, Dong; Yongheng, Zhang; Zhongmin, Lu; Kaihua, Zhai; Xiaohong, Liu

2014-04-01

Brain ischemia leads to severe disruption of the nervous system and recovery is often prolonged. Rehabilitative post-ischemia pharmacological treatment may therefore be important for behavioral recovery, especially for cognition and motor behavior. The present study investigated the effects of combined vinpocetine and ozagrel administration on the behavioral recovery of rats from global brain ischemia. The results suggest that the combined treatment leads to significantly better improvement compared to single drug administration. We conclude that the combined use of vinpocetine and ozagrel may provide beneficial effects to patients suffering from brain ischemia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

PubMed

Ma, Hu-Sai; Ma, Ju-Hua; Xue, Feng-Lai; Fu, Xiang-Ning; Zhang, Ni

2016-12-01

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

Clay-starch combination for micropollutants removal from wastewater treatment plant effluent.

PubMed

Mohd Amin, M F; Heijman, S G J; Rietveld, L C

2016-01-01

In this study, a new, more effective and cost-effective treatment alternative is investigated for the removal of pharmaceuticals from wastewater treatment plant effluent (WWTP-eff). The potential of combining clay with biodegradable polymeric flocculants is further highlighted. Flocculation is viewed as the best method to get the optimum outcome from clay. In addition, flocculation with cationic starch increases the biodegradability and cost of the treatment. Clay is naturally abundantly available and relatively inexpensive compared to conventional adsorbents. Experimental studies were carried out with existing naturally occurring pharmaceutical concentrations found and measured in WWTP-eff with atrazine spiking for comparison between the demineralised water and WWTP-eff matrix. Around 70% of the total measured pharmaceutical compounds were removable by the clay-starch combination. The effect of clay with and without starch addition was also highlighted.

The effects of luminance contrast, colour combinations, font, and search time on brand icon legibility.

PubMed

Ko, Ya-Hsien

2017-11-01

This study explored and identified the effects of luminance contrast, colour combinations, font, and search time on brand icon legibility. A total of 108 participants took part in the experiment. As designed, legibility was measured as a function of the following independent variables: four levels of luminance contrast, sixteen target/background colour combinations, two fonts, and three search times. The results showed that a luminance contrast of 18:1 provided readers with the best legibility. Yellow on black, yellow on blue, and white on blue were the three most legible colour combinations. One of this study's unique findings was that colour combinations may play an even more important role than luminance contrast in the overall legibility of brand icon design. The 12-s search time corresponded with the highest legibility. Arial font was more legible than Times New Roman. These results provide some guidance for brand icon and product advertisement design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combined treatment with oral finasteride and topical minoxidil in male androgenetic alopecia: a randomized and comparative study in Chinese patients.

PubMed

Hu, Ruiming; Xu, Feng; Sheng, Youyu; Qi, Sisi; Han, Yumei; Miao, Ying; Rui, Wenlong; Yang, Qinping

2015-01-01

Finasteride at 1 mg/day and 5% topical minoxidil are effective in male androgenetic alopecia (MAGA). However, studies describing their effects in Chinese individuals are scarce. 450 Chinese MAGA patients were randomly assigned to receive finasteride (n = 160), minoxidil (n = 130) and combined medication (n = 160) for 12 months. The patients returned to the clinic every 3 months for efficacy evaluation. And efficacy was evaluated in 428 men at treatment end, including 154, 122, and 152 in the finasteride, 5% minoxidil, and combination groups, respectively. All groups showed similar baseline characteristics, including age at enrollment, and duration and severity of alopecia (p > 0.05). At 12 months, 80.5, 59, and 94.1% men treated with finasteride, 5% minoxidil and the combination therapy showed improvement, respectively. Adverse reactions were rare (finasteride, 1.8%; minoxidil, 6.1%), and disappeared right after drug withdrawal. In conclusion, finasteride is superior to 5% minoxidil, while the combined medication showed the best efficacy. © 2015 Wiley Periodicals, Inc.

Clinical experience with trimegestone as a new progestin in HRT.

PubMed

Grubb, Gary; Spielmann, Daniele; Pickar, James; Constantine, Ginger

2003-11-01

Trimegestone (TMG) is a novel, 19-norpregnane progestin, which demonstrates endometrial selectivity with a reduced progestin-related side effect profile when compared to several other currently marketed progestins. TMG has been studied in combination with 17beta-estradiol (17beta-E2) and conjugated equine estrogens (CEE). TMG-containing HRT agents were effective in relieving vasomotor symptoms and providing protection from endometrial hyperplasia with < or =1% hyperplasia. In clinical trials with sequential regimens, TMG provided predictable withdrawal bleeding associated with a low incidence of irregular and prolonged bleeding. Clinical studies of continuous combined regimens of estrogen/TMG combinations demonstrated high levels of amenorrhea. Both 17beta-E2 and CEE/TMG combinations have shown improved bone mineral density and quality-of-life assessments. Both continuous combined and sequential regimens of 17beta-E2/TMG and CEE/TMG have a favorable clinical profile. TMG provides an important new option for the treatment of postmenopausal symptoms and the prevention of osteoporosis.

Development of fat-reduced sausages: Influence of binary and ternary combinations of carrageenan, inulin, and bovine plasma proteins.

PubMed

Baracco, Yanina; Rodriguez Furlán, Laura T; Campderrós, Mercedes E

2017-04-01

The aim of this work was to study the influence of the binary and ternary combinations of bovine plasma proteins (BPP), inulin (I) and κ-carrageenan (C) in the overall quality of fat-reduced sausages. The influence of these components over different properties (chemical composition, weight loss after cooking, emulsion stability, texture profile and sensory analysis of fat-reduced sausages) was studied and compared against two samples, one without fat reduction and another a fat-reduced sample without addition of texturing agents. In this sense, a full factorial experimental design of two levels with central point was used. The samples containing BPP+I and BPP+C showed a synergy in which the binary combinations presented higher values of moisture and protein content than the samples containing the individual components. The reduction of fat content increases the values of hardness and decreases the values of springiness. Samples with 5% BPP (w/w) and binary combinations of BPP+C and BPP+I had the best stability values (low total fluid loss), demonstrating a significant synergistic effect by combining BPP+C. Similar results were obtained from the study of weight loss after cooking. However, both studies showed a destabilization of the sample BPP+I+C as emulsion stability decreased and weight loss increased after cooking compared to binary combinations ( P < 0.05). Samples with a binary combination of BPP+C and BPP+I do not present a statistically significant difference in the chewiness with respect to a not-fat-reduced commercial sample ( P > 0.05). The less acceptable sample for flavor and texture was the one containing only BPP. However, when BPP combined with I or C, a major acceptability was obtained, demonstrating the synergistic effect of these binary combinations. Therefore, our studies revealed that the binary combinations of BPP with I or C are good alternatives for the development of fat-reduced sausage.

Antibiotic effects against periodontal bacteria in organ cultured tissue.

PubMed

Takeshita, Masaaki; Haraguchi, Akira; Miura, Mayumi; Hamachi, Takafumi; Fukuda, Takao; Sanui, Terukazu; Takano, Aiko; Nishimura, Fusanori

2017-02-01

Mechanical reduction of infectious bacteria by using physical instruments is considered the principal therapeutic strategy for periodontal disease; addition of antibiotics is adjunctive. However, local antibiotic treatment, combined with conventional mechanical debridement, has recently been shown to be more effective in periodontitis subjects with type 2 diabetes. This suggests that some bacteria may invade the inflamed inner gingival epithelium, and mechanical debridement alone will be unable to reduce these bacteria completely. Therefore, we tried to establish infected organ culture models that mimic the inner gingival epithelium and aimed to see the effects of antibiotics in these established models. Mouse dorsal skin epithelia were isolated, and periodontal bacteria were injected into the epithelia. Infected epithelia were incubated with test antibiotics, and colony-forming ability was evaluated. Results indicated that effective antibiotics differed according to injected bacteria and the bacterial combinations tested. Overall, in organ culture model, the combination of amoxicillin or cefdinir and metronidazole compensate for the effects of less effective bacterial combinations on each other. This in vitro study would suggest effective periodontal treatment regimens, especially for severe periodontitis.

Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions

PubMed Central

Van Deun, Katrijn; Thorrez, Lieven; van den Berg, Robert A.; Smilde, Age K.; Van Mechelen, Iven

2015-01-01

Motivation Experiments in which the effect of combined manipulations is compared with the effects of their pure constituents have received a great deal of attention. Examples include the study of combination therapies and the comparison of double and single knockout model organisms. Often the effect of the combined manipulation is not a mere addition of the effects of its constituents, with quite different forms of interplay between the constituents being possible. Yet, a well-formalized taxonomy of possible forms of interplay is lacking, let alone a statistical methodology to test for their presence in empirical data. Results Starting from a taxonomy of a broad range of forms of interplay between constituents of a combined manipulation, we propose a sound statistical hypothesis testing framework to test for the presence of each particular form of interplay. We illustrate the framework with analyses of public gene expression data on the combined treatment of dendritic cells with curdlan and GM-CSF and show that these lead to valuable insights into the mode of action of the constituent treatments and their combination. Availability and Implementation R code implementing the statistical testing procedure for microarray gene expression data is available as supplementary material. The data are available from the Gene Expression Omnibus with accession number GSE32986. PMID:25965065

Not Just a Sum? Identifying Different Types of Interplay between Constituents in Combined Interventions.

PubMed

Van Deun, Katrijn; Thorrez, Lieven; van den Berg, Robert A; Smilde, Age K; Van Mechelen, Iven

2015-01-01

Experiments in which the effect of combined manipulations is compared with the effects of their pure constituents have received a great deal of attention. Examples include the study of combination therapies and the comparison of double and single knockout model organisms. Often the effect of the combined manipulation is not a mere addition of the effects of its constituents, with quite different forms of interplay between the constituents being possible. Yet, a well-formalized taxonomy of possible forms of interplay is lacking, let alone a statistical methodology to test for their presence in empirical data. Starting from a taxonomy of a broad range of forms of interplay between constituents of a combined manipulation, we propose a sound statistical hypothesis testing framework to test for the presence of each particular form of interplay. We illustrate the framework with analyses of public gene expression data on the combined treatment of dendritic cells with curdlan and GM-CSF and show that these lead to valuable insights into the mode of action of the constituent treatments and their combination. R code implementing the statistical testing procedure for microarray gene expression data is available as supplementary material. The data are available from the Gene Expression Omnibus with accession number GSE32986.

Antinociceptive Effect of Racemic Flurbiprofen and Caffeine Co-Administration in an Arthritic Gout-Type Pain in Rats.

PubMed

Liévano-Reyes, Ricardo; Pérez-Méndez, Hermínia Ines; Solís-Oba, Aida; Jaramillo-Morales, Osmar Antonio; Espinosa-Juárez, Josué Vidal; López-Muñoz, Francisco Javier

2016-06-01

Preclinical Research Drug combinations are routinely used in the treatment of pain. In drug associations, adjuvants such as caffeine, are employed with different non-steroidal anti-inflammatories drugs (NSAIDs), however, at present does not exist studies showing the effect of the combination of racemic flurbiprofen (rac-Flur) in association with caffeine. The objective of this work was to evaluate the combination of rac-Flur + caffeine oral in arthritic gout-type pain in rats. The antinociceptive effects of the rac-Flur alone and in combination with caffeine were analyzed on a pain-induced functional impairment model in rat. rac-Flur induced a dose-dependent antinociceptive effect and caffeine did not present any effect. The combination of rac-Flur and caffeine achieve a higher percentage of antinociceptive effect compared with the individual administration of rac-Flur. The dose-response curve (DRCs) shows that the combination of rac-Flur (31.6 mg/kg) + caffeine (17.8 mg/kg) exhibited the maximal antinociceptive efficacy (294.0 ± 21.2 area units), while rac-Flur alone (31.6 mg/kg) showed 207.2 ± 35.2 au, thus indicating an increase in efficacy (potentiation). Furthermore, the DRCs of the combinations presented a displacement to the left, indicating a change in the potency. Caffeine is able to increase the effect of rac-Flur in the arthritic gout-type pain in rats. Drug Dev Res 77 : 192-198, 2016.   © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Treatment with the use of microcurrent lymphatic drainage physiotherapy during the postoperative period following rhinoplastic surgery].

PubMed

Aleksanyan, T A; Kazantsev, E V

The objective of the present study was to evaluate the effectiveness of the combined treatment of the patients who had undergone either primary or secondary rhinoplastic surgery with the use of photo- and magnetic therapy in comparison with the effectiveness of phototherapy in the combination with microcurrent therapy. The patients were divided into four groups depending on the type of the surgical intervention and the mode of the combined physiotherapeutic treatment. All the patients were given combined physiotherapeutic treatment in addition to the standard pharmacotherapy starting from the second day of the postoperative period. The patients of groups 1 and 3 received phototherapy in the combination with magnetic therapy while those in groups 2 and 4 were treated by phototherapy in the combination with microcurrent lymphatic drainage physiotherapy. It was shown that the different combinations of physiotherapeutic modalities during the postoperative period following primary «closed» rhinoplasty were not different significantly in terms of effectiveness. After secondary «closed» rhinoplasty, the combination of phototherapy with the application of microcurrents looks more preferable. It is concluded that microcurrent lymphdraining physiotherapy should be regarded as the priority component of the combined physiotherapeutic treatment during the postoperative period following secondary «closed» rhinoplasty.

Combination of fluconazole with silver nanoparticles produced by Fusarium oxysporum improves antifungal effect against planktonic cells and biofilm of drug-resistant Candida albicans.

PubMed

Longhi, Carline; Santos, Jussevania Pereira; Morey, Alexandre Tadachi; Marcato, Priscyla Daniely; Durán, Nelson; Pinge-Filho, Phileno; Nakazato, Gerson; Yamada-Ogatta, Sueli Fumie; Yamauchi, Lucy Megumi

2016-05-01

Silver nanoparticles (AgNPs) have been extensively studied because of their anti-microbial potential. Here, we evaluated the effect of biologically synthesized silver nanoparticles (AgNPbio) alone and in combination with fluconazole (FLC) against planktonic cells and biofilms of FLC-resistant Candida albicans AgNPbio exhibited a fungicidal effect, with a minimal inhibitory concentration (MIC) and fungicidal concentration ranging from 2.17 to 4.35 μg/ml. The combination of AgNPbio and FLC reduced the MIC of FLC around 16 to 64 times against planktonic cells of allC. albicans There was no significant inhibitory effect of AgNPbio on biofilm cells. However, FLC combined with AgNPbio caused a significant dose-dependent decrease in the viability of both initial and mature biofilm. All concentrations of AgNPbio, alone or in combination with FLC, were not cytotoxic to mammalian cells.The results highlight the effectiveness of the combination of AgNPbio with FLC against FLC-resistant C. albicans. © The Author 2015. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis.

PubMed

Farris, Manuela; Bastianelli, Carlo; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-10-01

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

PubMed

Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

2014-11-30

Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when outcomes were measured on different scales. We included eleven studies, involving 1307 participants in this review. We also identified one ongoing study, and two additional ongoing studies that may be eligible for inclusion. Studies recruited participants with different severities of disorder and with a variety of comorbid disorders, including anxiety and substance use disorder, therefore limiting the comparability of the results. Regarding the risk of bias in studies, just under half the studies had adequate allocation concealment (there was insufficient information to determine allocation concealment in the remainder), outcome assessors were blind to the participants' intervention in six studies, and in general, studies reported on incomplete data analysis methods, mainly using intention-to-treat (ITT) analyses. For the majority of outcomes there were no statistically significant differences between the interventions compared. There was limited evidence (based on two studies involving 220 participants) that antidepressant medication was more effective than psychotherapy on measures of clinician defined remission immediately post-intervention (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the medication group and 53.7% in the psychotherapy group rated as being in remission. There was limited evidence (based on three studies involving 378 participants) that combination therapy was more effective than antidepressant medication alone in achieving higher remission from a depressive episode immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of participants treated with combination therapy and 57.8% of participants treated with medication, rated as being in remission. There was no evidence to suggest that combination therapy was more effective than psychological therapy alone, based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI 0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in various ways across studies and could not be combined in meta-analyses. However, some trials measured suicidal ideation using standardised assessment tools suitable for meta-analysis. In one study involving 188 participants, rates of suicidal ideation were significantly higher in the antidepressant medication group (18.6%) compared with the psychological therapy group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at six to nine months (OR 0.26, 95% CI 0.07 to 0.98), with 13.6% of participants in the medication group and 3.9% of participants in the psychological therapy group reporting suicidal ideation. It was unclear what the effect of combination therapy was compared with either antidepressant medication alone or psychological therapy alone on rates of suicidal ideation. The impact of any of the assigned treatment packages on drop out was also mostly unclear across the various comparisons in the review.Limited data and conflicting results based on other outcome measures make it difficult to draw conclusions regarding the effectiveness of any specific intervention based on these outcomes. There is very limited evidence upon which to base conclusions about the relative effectiveness of psychological interventions, antidepressant medication and a combination of these interventions. On the basis of the available evidence, the effectiveness of these interventions for treating depressive disorders in children and adolescents cannot be established. Further appropriately powered RCTs are required.

Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults

PubMed Central

Li, Bing; Zhu, Xinyi; Hou, Jianhua; Chen, Tingji; Wang, Pengyun; Li, Juan

2016-01-01

As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR-OON-16007793. PMID:27375521

Effects of Combination Therapy With Immunomodulators on Trough Levels and Antibodies Against Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Disease: A Meta-analysis.

PubMed

Qiu, Yun; Mao, Ren; Chen, Bai-Li; Zhang, Sheng-Hong; Guo, Jing; He, Yao; Zeng, Zhi-Rong; Ben-Horin, Shomron; Chen, Min-Hu

2017-09-01

It is not clear whether combination therapy with immunomodulators affects the immunogenicity of tumor necrosis factor (TNF) antagonists in patients with inflammatory bowel disease. We performed a meta-analysis to quantify the effects of combined immunomodulator therapy on the presence of antibodies against TNF antagonists (antidrug antibodies [ADAs]) and trough levels of anti-TNF agents. We systematically searched publication databases for studies that reported prevalence of ADAs in patients who received anti-TNF agents. Raw data from studies that met the inclusion criteria were pooled to determine effect estimates. We performed subgroup and metaregression analyses to determine the level of heterogeneity among study outcomes. We analyzed findings from 35 studies that met inclusion criteria (results reported from 6790 patients with inflammatory bowel disease). The pooled risk ratio for formation of ADAs in patients receiving combined therapy with immunomodulators, versus that of patients receiving anti-TNF monotherapy, was 0.49 (95% confidence interval, 0.41-0.59; P < .001). However, the pooled analysis did not demonstrate a significant difference in trough levels of anti-TNF agents between patients with versus without concurrent use of immunomodulators (standardized mean difference, 0.11; 95% confidence interval, 0.19-0.41; P = .47). Subgroup analyses of patients treated with different TNF antagonists revealed no difference in the formation of ADAs (P = .50 for interaction); the protective effect of immunomodulators did not differ with type of drug patients were given (methotrexate vs thiopurines), or assay for ADA. We observed heterogeneity only among studies of patients with ulcerative colitis (I 2  = 76%). Funnel plot and Egger test analyses indicated publication bias in the studies (P = .001). In a meta-analysis of published studies, we associated combined treatment with immunomodulators with reduced risk of formation of antibodies against TNF antagonists in patients with inflammatory bowel disease. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Bio-enhancing Effect of Piperine with Metformin on Lowering Blood Glucose Level in Alloxan Induced Diabetic Mice

PubMed Central

Atal, Shubham; Atal, Sarjana; Vyas, Savita; Phadnis, Pradeep

2016-01-01

Background: Diabetes mellitus is the most rampant metabolic pandemic of the 21st century. Piperine, the chief alkaloid of Piper nigrum (black pepper) is widely used in alternative and complementary therapies has been extensively studied for its bio-enhancing property. Objective: To evaluate the bio-enhancing effect of piperine with metformin in lowering blood glucose levels in alloxan-induced diabetic mice. Materials and Methods: Piperine was isolated from an extract of fruits of P. nigrum. Alloxan-induced (150 mg/kg intraperitoneal) diabetic mice were divided into four groups. Group I (control 2% gum acacia 2 g/100 mL), Group II (metformin 250 mg/kg), Group III (metformin and piperine 250 mg/kg + 10 mg/kg), and Group IV (metformin and piperine 125 mg/kg + 10 mg/kg). All the drugs were administered orally once daily for 28 days. Blood glucose levels were estimated at day 0, day 14, and end of the study (day 28). Results: The combination of piperine with therapeutic dose of metformin (10 mg/kg + 250 mg/kg) showed significantly more lowering of blood glucose level as compared to metformin alone on both 14th and 28th day (P < 0.05). Piperine in combination with sub-therapeutic dose of metformin (10 mg/kg + 125 mg/kg) showed significantly more lowering of blood glucose as compared to control group and also showed greater lowering of blood glucose as compared to metformin (250 mg/kg) alone. Conclusion: Piperine has the potential to be used as a bio-enhancing agent in combination with metformin which can help reduce the dose of metformin and its adverse effects. SUMMARY Piperine is known for its bioenhancing property. This study evaluates the effect of piperine in combination with oral antidiabetic drug metformin. Drugs were administered for 28 days in alloxan induced diabetic mice and blood glucose lowering effect was seen. Results showed significantly better effect of combination of piperine with therapeutic dose of metformin in comparison to metformin alone. Piperine in combination with subtherapeutic dose of metformin also showed better effect than therapeutic dose of metformin. Piperine, thus shows potential to be used as bioenhancer in combination with metformin. PMID:26941537

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Combined effects of prevention and quarantine on a breakout in SIR model.

PubMed

Kato, Fuminori; Tainaka, Kei-Ichi; Sone, Shogo; Morita, Satoru; Iida, Hiroyuki; Yoshimura, Jin

2011-01-01

Recent breakouts of several epidemics, such as flu pandemics, are serious threats to human health. The measures of protection against these epidemics are urgent issues in epidemiological studies. Prevention and quarantine are two major approaches against disease spreads. We here investigate the combined effects of these two measures of protection using the SIR model. We use site percolation for prevention and bond percolation for quarantine applying on a lattice model. We find a strong synergistic effect of prevention and quarantine under local interactions. A slight increase in protection measures is extremely effective in the initial disease spreads. Combination of the two measures is more effective than a single protection measure. Our results suggest that the protection policy against epidemics should account for both prevention and quarantine measures simultaneously.

MODELING MICROBUBBLE DYNAMICS IN BIOMEDICAL APPLICATIONS*

PubMed Central

CHAHINE, Georges L.; HSIAO, Chao-Tsung

2012-01-01

Controlling microbubble dynamics to produce desirable biomedical outcomes when and where necessary and avoid deleterious effects requires advanced knowledge, which can be achieved only through a combination of experimental and numerical/analytical techniques. The present communication presents a multi-physics approach to study the dynamics combining viscous- in-viscid effects, liquid and structure dynamics, and multi bubble interaction. While complex numerical tools are developed and used, the study aims at identifying the key parameters influencing the dynamics, which need to be included in simpler models. PMID:22833696

Combination of curcumin and green tea catechins prevents dimethylhydrazine-induced colon carcinogenesis.

PubMed

Xu, Gang; Ren, Guijie; Xu, Xia; Yuan, Huiqing; Wang, Zhenzheng; Kang, Ludong; Yu, Wenguang; Tian, Keli

2010-01-01

The chemopreventive effects of curcumin and green tea catechins individually and in combination on 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis were studied in male Wister rats following 32 weeks of dietary treatment. The incidence, number and size of colorectal cancer were measured. Colorectal aberrant crypt foci (ACF) were analyzed by methylene blue staining. Proliferation indices and apoptotic indices were determined by PCNA immunostaining and TUNEL assay, respectively. The results showed that dietary curcumin, catechins and combination administration significantly inhibited the total number of ACF per rat. The combination treatment displayed the most potent inhibitory effect, while there was no difference of inhibition between curcumin and catechins-treated groups. The incidence of colorectal cancer in the treated groups was significantly lower than that of positive control group. Compared with the positive control group, the proliferation index was significantly decreased and the apoptotic index was significantly increased in all treatment groups, while the effect of the combination was the greatest among the treated groups. Our findings suggest that the combination of curcumin and catechins may produce a synergistic colon cancer-preventative effect that would be more potent than each of the compounds alone. Copyright 2009 Elsevier Ltd. All rights reserved.

Effects of Plantar Flexor Muscle Static Stretching Alone and Combined With Massage on Postural Balance.

PubMed

Hemmati, Ladan; Rojhani-Shirazi, Zahra; Ebrahimi, Samaneh

2016-10-01

To evaluate and compare the effects of stretching and combined therapy (stretching and massage) on postural balance in people aged 50 to 65 years. Twenty-three subjects participated in this nonrandomized clinical trial study. Each participant randomly received plantar flexor muscle stretching (3 cycles of 45 seconds with a 30-second recovery period between cycles) alone and in combination with deep stroking massage (an interval of at least 30 minutes separated the two interventions). The data were recorded with a force platform immediately after each condition with eyes open and closed. The center of pressure displacement and velocity along the mediolateral and anteroposterior axes were calculated under each condition. The data were analyzed with multiple-pair t-tests. The center of pressure displacement and velocity along the mediolateral axis increased after both stretching and the combined intervention. There were significant differences in both values between participants in the stretching and combined interventions (p<0.05). Plantar flexor muscle stretching (for 45 seconds) combined with deep stroking massage may have more detrimental effects on postural balance than stretching alone because each intervention can intensify the effects of the other.

Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.

PubMed

Chou, Ting-Chao

2006-09-01

The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

Effect of combined application insulin and insulin detemir on continous glucose monitor in children with type 1 diabetes mellitus.

PubMed

Chen, Xiao-Yun; Dong, Qing; Li, Gui-Mei

2015-01-01

Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action, which could strengthen the effects of insulin. This study aims to explore the effects of insulin combined with insulin detemir on the continous glucose in children with type 1 diabetes mellitus. In this study, 150 patients with type 1 diabetes enrolled were included and randomly divided into 3 groups: insulin group (group A), insulin detemir group (group B) and insulin combined with insulin detemir group (group C). Each subject underwent 72 h of continuous glucose monitoring (CGM). MAGE, HbA1c and Noctumal Hypoglycemia levels were examined by using the ELISA kits. The body weight changes were also detected in this study. The results indicated that the information including age, body weight, disease duration and glucose level and HbA1c percentage on the start time point among three groups indicated no statistical differences. Insulin combined with insulin detemir decrease MAGE and HbA1c level in Group C compared to Group A and Group A (P < 0.05). Insulin combined with insulin detemir decreas noctumal hypoglycemia levels and body weight changes (P < 0.05). In conclusion, this study confirmed efficacy of insulin detemir by demonstrating non-inferiority of insulin detemir compared with insulin with respect to HbA1c, with an improved safety profile including significantly fewer hypoglycaemic episodes and less undesirable weight gain in children.

The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

PubMed

Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

2015-01-01

Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n = 1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study groups showed distinct decreases in office BP at 4 week (p < 0.001) and the antihypertensive effects were sustained to 12 week (p < 0.001). The percentage of patients achieving BP < 140/90 mmHg was ∼70% in either group. Proteinuria and estimated glomerular filtration rate (eGFR) were significantly improved in hypertensive patients with baseline eGFR <60 ml/min/1.73 m(2). Serum uric acid was reduced either by adding AML or IRB, and the reductions were prominent in patients with serum uric acid >7 mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.

Docosahexaenoic Acid Sensitizes Leukemia Lymphocytes to Barasertib and Everolimus by ROS-dependent Mechanism Without Affecting the Level of ROS and Viability of Normal Lymphocytes.

PubMed

Zhelev, Zhivko; Ivanova, Donika; Lazarova, Desislava; Aoki, Ichio; Bakalova, Rumiana; Saga, Tsuneo

2016-04-01

The aim of the present study was: (i) to investigate the possibility of sensitizing leukemia lymphocytes to anticancer drugs using docosahexaenoic acid (DHA); (ii) to find combinations with synergistic cytotoxic effect on leukemia lymphocytes, without or with only very low cytotoxicity towards normal lymphocytes; (iii) and to clarify the role of reactive oxygen species (ROS) in the induction of apoptosis and cytotoxicity by such combinations. The study covered 15 anticancer drugs, conventional and new-generation. Well-expressed synergistic cytotoxic effects were observed after treatment of leukemia lymphocytes (Jurkat) with DHA in combination with: barasertib, lonafarnib, everolimus, and palbociclib. We selected two synergistic combinations, DHA with everolimus or barasertib, and investigated their effects on viability of normal lymphocytes, as well as on the production of ROS and induction of apoptosis in both cell lines (leukemia and normal). At the selected concentrations, DHA, everolimus and barasertib (applied separately) were cytotoxic towards leukemia lymphocytes, but not normal lymphocytes. In leukemia cells, the cytotoxicity of combinations was accompanied by strong induction of apoptosis and production of ROS. In normal lymphocytes, drugs alone and in combination with DHA did not affect the level of ROS and did not induce apoptosis. To our knowledge, the present study is the first to report synergistic ROS-dependent cytotoxicity between DHA and new-generation anticancer drugs, such as everolimus and barasertib, that is cancer cell-specific (particularly for acute lymphoblastic leukemia cells Jurkat). These combinations are harmless to normal lymphocytes and do not induce abnormal production of ROS in these cells. The data suggest that DHA could be used as a supplementary component in anticancer chemotherapy, allowing therapeutic doses of everolimus and barasertib to be reduced, minimizing their side-effects. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Fast dissolving drug-drug eutectics with improved compressibility and synergistic effects.

PubMed

Thipparaboina, Rajesh; Thumuri, Dinesh; Chavan, Rahul; Naidu, V G M; Shastri, Nalini R

2017-06-15

Combinational therapy has become increasingly popular in recent times due to various advantages like greater therapeutic effect, reduced number of prescriptions, lower administrative costs, and an increase in patient compliance. Drug-drug multicomponent adducts could help in combination of drugs at supramolecular level. Two drug-drug eutectics of etodolac with paracetamol (EP) and etodolac with propranolol hydrochloride (EPHC) were successfully designed and synthesized for the first time. These eutectics significantly improved dissolution and material properties. A 6 to 9 fold enhancement in % dissolution efficiency was found at 1min suggesting the fast dissolving capabilities of the eutectic mixtures when compared to plain drug. In addition, eutectic mixtures have shown improved hardness compared to plain drugs. EP and EPHC have shown around 5 fold and 3 fold improvements in hardness respectively at 10MPa when compared to plain etodolac. Cell culture studies have shown improved effects of EP. Western blotting analysis revealed that the said combination successfully reduced various inflammatory mediators like TNF-α, COX-2 and IL-6. Whereas, the eutectic combination EPHC has shown enhanced cytotoxic effects with synergistic combination index and favorable dose reduction index. The generated multi-component systems EP and EPHC with fast dissolving capabilities, improved hardness at lower pressures and synergistic effects represent prospective combinations for effective treatment of osteoarthritis and cancer chemotherapy respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

PubMed Central

Arnold, L. Eugene; Hodgkins, Paul; Caci, Hervé; Kahle, Jennifer; Young, Susan

2015-01-01

Background Evaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood. Methods A systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment. Results The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length. Conclusions While the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age or longer durations did not markedly affect proportion of improved outcomes reported, but measurement of outcomes long periods after treatment cessation may attenuate results. PMID:25714373

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research.

PubMed

Clemens, Kelly J; McGregor, Iain S; Hunt, Glenn E; Cornish, Jennifer L

2007-01-01

The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') and methamphetamine (METH, 'ice', 'speed') are increasingly popular drugs amongst party-drug users. Studies with humans have investigated the acute and possible long-term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long-term effects of MDMA and METH on brain and behaviour. Self-administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long-term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a 'neurotoxic' effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long-term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs.

Chemical composition and antioxidant properties of Laurus nobilis L. and Myrtus communis L. essential oils from Morocco and evaluation of their antimicrobial activity acting alone or in combined processes for food preservation.

PubMed

Cherrat, Lamia; Espina, Laura; Bakkali, Mohammed; García-Gonzalo, Diego; Pagán, Rafael; Laglaoui, Amin

2014-04-01

This study describes the antioxidant and antimicrobial activity of Laurus nobilis L. and Myrtus communis L. essential oils (EOs). This is the first report of the synergistic antimicrobial effect of these EOs in combination with physical food preservation treatments. EOs obtained by steam distillation from aerial parts of Laurus nobilis and Myrtus communis were analysed by using gas chromatography-mass spectrometry. The main compounds were 1,8-cineole and 2-carene (L. nobilis EO); and myrtenyl acetate, 1,8-cineole and α-pinene (M. communis EO). L. nobilis EO showed higher antioxidant activity than M. communis EO in three complementary antioxidant tests. Although antimicrobial activity tests demonstrated the effectiveness of L. nobilis EO and the lack of bactericidal effect of M. communis EO, synergistic lethal effects were observed when combining each EO (0.2 µL mL(-1)) with mild heat (54°C for 10 min) or high hydrostatic pressure (175-400 MPa for 20 min). In contrast, combination of EOs with pulsed electric fields (30 kV cm(-1) for 25 pulses) showed no additional effects. This study shows the great potential of these EOs in combined treatments with mild heat and high hydrostatic pressure to obtain a higher inactivation of foodborne pathogens, which might help in the design of safe processes applied at low intensity. © 2013 Society of Chemical Industry.

Effects of Azilsartan, Aliskiren or their Combination on High Fat Diet-induced Non-alcoholic Liver Disease Model in Rats.

PubMed

Hussain, Saad Abdulrahman; Utba, Rabab Mohammed; Assumaidaee, Ajwad Muhammad

2017-08-01

In addition to its role in regulation of blood pressure, fluid and electrolyte homeostasis, the renin-angiotensin system (RAS) components were expressed in many other tissues suggesting potential roles in their functions. The present study aims to evaluate the protective effect aliskiren, when used alone or in combination with azilsartan against high fat diet-induced liver disease in rats. Thirty-two Wistar male rats, weighing 150-200 gm were allocated evenly into four groups and treated as follow: group I, rats were fed a specially formulated high-fat diet for 8 weeks to induce non-alcoholic liver disease and considered as control group; groups II, III and IV, the rats were administered azilsartan (0.5 mg/kg), aliskiren (25 mg/kg) or their combination orally via gavage tube once daily, and maintained on high fat diet for 8 weeks. The possible treatment outcome was evaluated through measuring serum levels of glucose, insulin, lipid profile, TNF-α, IL-1β and liver enzymes. Additionally, the liver tissue contents of glycogen and lipids and histological changes were also evaluated. The results showed that azilsartan significantly improves the studied markers greater than aliskiren, and their combination o has no additive or synergistic effects on the activity of each one of them. Both azilsartan and aliskiren protects the rats against high-fat diet induced NAFLD with predominant effects for the former, and their combination showed no beneficial synergistic or additive effects.

Geophysical experiments for the pre-reclamation assessment of industrial and municipal waste landfills

NASA Astrophysics Data System (ADS)

Balia, R.; Littarru, B.

2010-03-01

Two examples of combined application of geophysical techniques for the pre-reclamation study of old waste landfills in Sardinia, Italy, are illustrated. The first one concerned a mine tailings basin and the second one a municipal solid waste landfill; both disposal sites date back to the 1970-80s. The gravity, shallow reflection, resistivity and induced polarization methods were employed in different combinations at the two sites, and in both cases useful information on the landfill's geometry has been obtained. The gravity method proved effective for locating the boundaries of the landfill and the shallow reflection seismic technique proved effective for the precise imaging of the landfill's bottom; conversely the electrical techniques, though widely employed for studying waste landfills, provided mainly qualitative and debatable results. The overall effectiveness of the surveys has been highly improved through the combined use of different techniques, whose individual responses, being strongly dependent on their specific basic physical characteristic and the complexity of the situation to be studied, did not show the same effectiveness at the two places.

Cannabinoids synergize with carfilzomib, reducing multiple myeloma cells viability and migration.

PubMed

Nabissi, Massimo; Morelli, Maria Beatrice; Offidani, Massimo; Amantini, Consuelo; Gentili, Silvia; Soriani, Alessandra; Cardinali, Claudio; Leoni, Pietro; Santoni, Giorgio

2016-11-22

Several studies showed a potential anti-tumor role for cannabinoids, by modulating cell signaling pathways involved in cancer cell proliferation, chemo-resistance and migration. Cannabidiol (CBD) was previously noted in multiple myeloma (MM), both alone and in synergy with the proteasome inhibitor bortezomib, to induce cell death. In other type of human cancers, the combination of CBD with Δ9-tetrahydrocannabinol (THC) was found to act synergistically with other chemotherapeutic drugs suggesting their use in combination therapy. In the current study, we evaluated the effects of THC alone and in combination with CBD in MM cell lines. We found that CBD and THC, mainly in combination, were able to reduce cell viability by inducing autophagic-dependent necrosis. Moreover, we showed that the CBD-THC combination was able to reduce MM cells migration by down-regulating expression of the chemokine receptor CXCR4 and of the CD147 plasma membrane glycoprotein. Furthermore, since the immuno-proteasome is considered a new target in MM and also since carfilzomib (CFZ) is a new promising immuno-proteasome inhibitor that creates irreversible adducts with the β5i subunit of immuno-proteasome, we evaluated the effect of CBD and THC in regulating the expression of the β5i subunit and their effect in combination with CFZ. Herein, we also found that the CBD and THC combination is able to reduce expression of the β5i subunit as well as to act in synergy with CFZ to increase MM cell death and inhibits cell migration. In summary, these results proved that this combination exerts strong anti-myeloma activities.

Repaglinide in combination therapy.

PubMed

Moses, R

2002-12-01

Type 2 diabetes mellitus (T2DM) is a progressive disorder requiring increasingly aggressive treatment to achieve and maintain target blood glucose concentrations in the presence of deteriorating insulin secretion and increasing insulin resistance. Diet and lifestyle modification are often sufficient initially; however, most patients eventually require pharmacological intervention. With disease progression, monotherapy becomes less effective, so combination therapy is required, using drugs with complementary modes of action to maximise glycaemic control. The prandial glucose regulator repaglinide has been studied in combination with metformin (an inhibitor of hepatic glucose production), neutral protamine Hagedorn (NPH)-insulin (which has a long duration of effect, but at the risk of early hypoglycaemia and late hyperglycaemia in the dosing interval) and three thiazolidinediones (TZDs--troglitazone, rosiglitazone and pioglitazone, which stimulate nuclear receptors to increase insulin sensitivity and reduce insulin resistance) in patients whose diabetes was inadequately controlled by previous monotherapy or combination therapy. The combination of repaglinide and metformin resulted in reduced fasting plasma glucose concentrations (by 2.2 mmol/l) and HbA1c (by 1.4%). Combination therapy with repaglinide and bedtime NPH-insulin resulted in reductions in fasting plasma glucose (by 5.4 mmol/l) and HbA1c (by 0.7%). The combination of repaglinide and each TZD also resulted in consistent decreases in fasting plasma glucose concentrations and HbA1c. No severe hypoglycaemic episodes were reported in the three studies. In conclusion, repaglinide has additive, and often synergistic, effects on glycaemic control when given in combination regimens and should be a valuable option in the management of patients with T2DM.

Ultrasound-guided Combined Fascial Plane Blocks as an Intervention for Pain Management after Laparoscopic Cholecystectomy: A Randomized Control Study

PubMed Central

Ramkiran, Seshadri; Jacob, Mathews; Honwad, Manish; Vivekanand, Desiraju; Krishnakumar, Mathangi; Patrikar, Seema

2018-01-01

Background: Pain associated with laparoscopic cholecystectomy is most severe during the first 24 h and the port sites are the most painful. Recent multimodal approaches target incisional pain instead of visceral pain which has led to the emergence of abdominal fascial plane blocks. This study embraces a novel combination of two independently effective fascial plane blocks, namely rectus sheath block and subcostal transversus abdominis plane (TAP) block to alleviate postoperative pain. Study Objective: The aim is to evaluate the effectiveness of the combination of rectus sheath block and subcostal TAP block, to compare its efficacy with that of subcostal TAP block alone and with conventional port site infiltration (PSI) in alleviating postoperative pain in patients undergoing laparoscopic cholecystectomy. Methodology: This prospective, randomized control, pilot study included 61 patients scheduled for elective laparoscopic cholecystectomy and distributed among three groups, namely Group 1: Combined subcostal TAP block with rectus sheath block (n = 20); Group 2: Oblique subcostal TAP block alone (n = 21); and Group 3: PSI group as an active control (n = 20). Results: Combined group had significantly lower pain scores, higher satisfaction scores, and reduced rescue analgesia both in early and late postoperative periods than the conventional PSI group. Conclusion: Ultrasound-guided combined fascial plane blocks is a novel intervention in pain management of patients undergoing laparoscopic cholecystectomy and should become the standard of care. PMID:29628547

Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary

PubMed Central

Takahashi, Ryoko; Mabuchi, Seiji; Kawano, Mahiru; Sasano, Tomoyuki; Matsumoto, Yuri; Kuroda, Hiromasa; Kozasa, Katsumi; Hashimoto, Kae; Sawada, Kenjiro; Kimura, Tadashi

2016-01-01

Objective The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype. Methods Using human ovarian CCC cell lines, the antitumor effects of lurbinectedin, SN-38, doxorubicin, cisplatin, and paclitaxel as single agents were assessed using the MTS assay. Then, the antitumor effects of combination therapies involving lurbinectedin and 1 of the other 4 agents were evaluated using isobologram analysis to examine whether these combinations displayed synergistic effects. The antitumor activity of each treatment was also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines. Finally, we determined the effects of mTORC1 inhibition on the antitumor activity of lurbinectedin-based chemotherapy. Results Lurbinectedin exhibited significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. An examination of mouse CCC cell xenografts revealed that lurbinectedin significantly inhibits tumor growth. Among the tested combinations, lurbinectedin plus SN-38 resulted in a significant synergistic effect. This combination also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Everolimus significantly enhanced the antitumor activity of lurbinectedin-based chemotherapies. Conclusions Lurbinectedin, a new agent that targets active transcription, exhibits antitumor activity in CCC when used as a single agent and has synergistic antitumor effects when combined with irinotecan. Our results indicate that lurbinectedin is a promising agent for treating ovarian CCC, both as a first-line treatment and as a salvage treatment for recurrent lesions that develop after platinum-based or paclitaxel treatment. PMID:26986199

Combining fisetin and ionizing radiation suppresses the growth of mammalian colorectal cancers in xenograft tumor models.

PubMed

Leu, Jyh-Der; Wang, Bo-Shen; Chiu, Shu-Jun; Chang, Chun-Yuan; Chen, Chien-Chih; Chen, Fu-Du; Avirmed, Shiirevnyamba; Lee, Yi-Jang

2016-12-01

Fisetin (3,7,3',4'-tetrahydroxyflavone), which belongs to the flavonoid group of polyphenols and is found in a wide range of plants, has been reported to exhibit a number of biological activities in human cancer cells, including antioxidant, anti-inflammatory, antiangiogenic, anti-invasive and antiproliferative effects. Although previous in vitro studies have shown that fisetin treatment increases the apoptotic rate and enhances the radiosensitivity of human colorectal cancer cells, the in vivo effects of fisetin on tumor growth remain unclear. In the present study a murine xenograft tumor model was employed to investigate the therapeutic effects of fisetin in combination with radiation on CT-26 colon cancer cells and human HCT116 colorectal cancer cells. This revealed that intratumoral injection of fisetin significantly suppressed the growth of CT-26 tumors compared with the untreated control group, but had little effect on the growth of HCT116 tumors. However, fisetin in combination with 2-Gy radiation enhanced tumor suppressor activity in murine colon and human colorectal xenograft tumors, as compared with 2-Gy fractionated radiation administered alone for 5 days and fisetin alone. Interestingly, fisetin downregulated the expression of the oncoprotein securin in a p53-independent manner. However, securin-null HCT116 tumors showed only moderate sensitivity to fisetin treatment, and the combination of fisetin and radiation did not significantly suppress securin-null HCT116 tumor growth compared with normal HCT116 tumors. Therefore, the role of securin in mediating the effect of fisetin on colorectal cancer growth warrants further investigation. In conclusion, the results of the current study provide important preclinical data for evaluating the efficacy of fisetin and radiation combination treatment as an adjuvant chemoradiotherapy for human colorectal cancers.

Synergistic effects of abiotic stresses in plants: a case study of nitrogen limitation and saturating light intensity in Arabidopsis thaliana.

PubMed

Cohen, Itay; Rapaport, Tal; Chalifa-Caspi, Vered; Rachmilevitch, Shimon

2018-05-22

Under natural conditions, plants are regularly exposed to combinations of stress factors. A common example is the conjunction between nitrogen (N) deficiency and excess light. The combined effect of stress factors is often ignored in studies using controlled conditions, possibly resulting in misleading conclusions. To address this issue, the current study examined the physiological behavior of Arabidopsis thaliana under the effect of varying nitrogen levels and light intensities. The joint influence of low N and excess light had an adverse effect on plant growth, chlorophyll and anthocyanin concentrations, photochemical capacity, and the abundance of proteins involved in carbon assimilation and anti-oxidative metabolism. In contrast, no adverse physiological responses were observed for plants under either nitrogen limitation or high light intensity conditions (i.e., single stress). The underline mechanisms for the increased growth in conditions of high light and sufficient nitrogen was due to a combination of chlorophyll accumulation and an increased number of proteins involved in C3 carbon assimilation, amino acids biosynthesis and chloroplast development. In contrast, combined stress conditions caused anthocyanin accumulation and increased number proteins involved in catabolism of lipids and amino acids as energy substrates. Ultimately switching plants from growth to survival. Our results suggest that an assessment of the physiological response to the combined effect of multiple stresses cannot be directly extrapolated from the physiological response to a single stress. Specifically, the synergistic interaction between N deficiency and saturating light in Arabidopsis plants could not have been modeled via only one of the stress factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

PubMed

AbouAssi, Hiba; Slentz, Cris A; Mikus, Catherine R; Tanner, Charles J; Bateman, Lori A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Penry, Lorrie E; Kraus, Erik A; Huffman, Kim M; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2015-06-15

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Combined Effects of Note-Taking/-Reviewing on Learning and the Enhancement through Interventions: A Meta-Analytic Review

ERIC Educational Resources Information Center

Kobayashi, Keiichi

2006-01-01

Meta-analyses of 33 studies were conducted to examine (1) how much the combination of taking and reviewing notes contributes to school learning, and (2) whether interventions in the note-taking/-reviewing procedure enhance note-taking/-reviewing effects, and if so, how much and under what conditions. Syntheses of findings from…

The Effect of Combining Analogy-Based Simulation and Laboratory Activities on Turkish Elementary School Students' Understanding of Simple Electric Circuits

ERIC Educational Resources Information Center

Unlu, Zeynep Koyunlu; Dokme, Ibilge

2011-01-01

The purpose of this study was to investigate whether the combination of both analogy-based simulation and laboratory activities as a teaching tool was more effective than utilizing them separately in teaching the concepts of simple electricity. The quasi-experimental design that involved 66 seventh grade students from urban Turkish elementary…

The Unique and Combined Effects of Homelessness and School Mobility on the Educational Outcomes of Young Children

ERIC Educational Resources Information Center

Fantuzzo, John W.; LeBoeuf, Whitney A.; Chen, Chin-Chih; Rouse, Heather L.; Culhane, Dennis P.

2012-01-01

This study examined the unique and combined associations of homelessness and school mobility with educational well-being indicators, as well as the mediating effect of absenteeism, for an entire cohort of third-grade students in Philadelphia. Using integrated archival administrative data from the public school district and the municipal Office of…

The Combined Effects of Online Planning and Task Structure on Complexity, Accuracy and Fluency of L2 Speech

ERIC Educational Resources Information Center

Javad Ahmadian, Mohammad; Tavakoli, Mansoor; Vahid Dastjerdi, Hossein

2015-01-01

This study investigates the combined effects of task-based careful online planning and the storyline structure of a task on second language performance (complexity, accuracy and fluency). Sixty intermediate EFL learners were randomly assigned to four groups (n = 15). Participants were asked to perform two tasks with different degrees of storyline…

L-Eye to Me: The Combined Role of Need for Cognition and Facial Trustworthiness in Mimetic Desires

ERIC Educational Resources Information Center

Treinen, Evelyne; Corneille, Olivier; Luypaert, Gaylord

2012-01-01

Recent studies showed that stimuli are evaluated more favourably when they are perceived to capture others' attention, an effect coined "mimetic desire". The aim of the present research was to examine the combined role of Need for Cognition and target's facial trustworthiness in this effect. Participants saw movie excerpts of trustworthy and…

Examining the Effects of SRSD in Combination with Video Self-Modeling on Writing by Third Grade Students with Learning Disabilities

ERIC Educational Resources Information Center

Miller, Katie M.; Little, Mary E.

2018-01-01

The purpose of this study was to determine the effectiveness of an instructional package, Self-Regulated Strategy Development, a cognitive strategy instructional model (POW + TREE), in combination with video self-modeling (VSM) on the improvement on the written expression of three third-grade students with learning disabilities (LD). This…

E-Learning Optimization: The Relative and Combined Effects of Mental Practice and Modeling on Enhanced Podcast-Based Learning--A Randomized Controlled Trial

ERIC Educational Resources Information Center

Alam, Fahad; Boet, Sylvain; Piquette, Dominique; Lai, Anita; Perkes, Christopher P.; LeBlanc, Vicki R.

2016-01-01

Enhanced podcasts increase learning, but evidence is lacking on how they should be designed to optimize their effectiveness. This study assessed the impact two learning instructional design methods (mental practice and modeling), either on their own or in combination, for teaching complex cognitive medical content when incorporated into enhanced…

Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

PubMed

Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

2011-11-01

The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

Effects of tramadol, clonazepam, and their combination on brain mitochondrial complexes.

PubMed

Mohamed, Tarek Mostafa; Ghaffar, Hamdy M Abdel; El Husseiny, Rabee M R

2015-12-01

The present study is an unsubstantiated qualitative assessment of the abused drugs-tramadol and clonazepam. The aim of this study is to evaluate whether the effects of tramadol, clonazepam, and their combination on mitochondrial electron transport chain (ETC) complexes were influential at therapeutic or at progressively increasing doses. The study comprised of a total of 70 healthy male rats, aged 3 months. According to the drug intake regimen, animals were divided into seven groups: control, tramadol therapeutic, clonazepam therapeutic, combination therapeutic, tramadol abuse, clonazepam abuse, and combination abuse group. At the end of the experiment, brain mitochondrial ETC complexes (I, II, III, and IV) were evaluated. Histopathological examinations were also performed on brain tissues. The results showed that groups that received tramadol (therapeutic and abuse) suffered from weight loss. Tramadol abuse group and combination abuse group showed significant decrease in the activities of I, III, and IV complexes but not in the activity of complex II. In conclusion, tramadol but not clonazepam has been found to partially inhibit the activities of respiratory chain complexes I, III, and IV but not the activity of complex II and such inhibition occurred only at doses that exceeded the maximum recommended adult human daily therapeutic doses. This result explains the clinical and histopathological effects of tramadol, such as seizures and red neurons (marker for apoptosis), respectively. © The Author(s) 2012.

Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress.

PubMed

Lu, Jun; Chen, Jian; Xu, Nianjun; Wu, Jun; Kang, Yani; Shen, Tingting; Kong, Hualei; Ma, Chao; Cheng, Ming; Shao, Zhifeng; Xu, Ling; Zhao, Xiaodong

2016-09-06

Application of cisplatin (DDP) for treating lung cancer is restricted due to its toxicity and lung cancer's drug resistance. In this study, we examined the effect of Jinfukang (JFK), an effective herbal medicine against lung cancer, on DDP-induced cytotoxicity in lung cancer cells. Morphologically, we observed that JFK increases DDP-induced pro-apoptosis in A549 cells in a synergistic manner. Transcriptome profiling analysis indicated that the combination of JFK and DDP regulates genes involved in apoptosis-related signaling pathways. Moreover, we found that the combination of JFK and DDP produces synergistic pro-apoptosis effect in other lung cancer cell lines, such as NCI-H1975, NCI-H1650, and NCI-H2228. Particularly, we demonstrated that AIFM2 is activated by the combined treatment of JFK and DDP and partially mediates the synergistic pro-apoptosis effect. Collectively, this study not only offered the first evidence that JFK promotes DDP-induced cytotoxicity, and activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress, but also provided a novel insight for improving cytotoxicity by combining JFK with DDP to treat lung cancer cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Citrus limonoids and curcumin additively inhibit human colon cancer cells.

PubMed

Chidambara Murthy, Kotamballi N; Jayaprakasha, G K; Patil, Bhimanagouda S

2013-04-30

In the current study, we examined the ability of limonoids, including limonin, limonin glucoside (LG) and curcumin, to inhibit proliferation of human colon cancer (SW480) cells. Additionally, we studied the effect of combining these two classes of natural compounds on inhibition of proliferation and the possible mode of cytotoxicity. The SW480 cells were treated with compounds individually and in combination to understand the effect on cell death, DNA fragmentation, caspase-3 activity and the expression of Bax, Bcl-2 and caspase-3 proteins. Results of cell proliferation assays suggest that combinations of limonoids with curcumin at three different ratios (1 : 3, 1 : 1 and 3 : 1) to a final concentration of 50 ppm demonstrated up to 96% inhibition of cell proliferation. The MTT assay results were also confirmed by counting viable cells. Further, incubation of cells with combinations of limonoids and curcumin resulted in elevation of total cellular caspase-3 activity by 3.5-4.0 fold along with a 2- to 4-fold increase in the Bax/Bcl-2 ratio. The expression of pro-caspase-3 and its cleaved products in cells treated with curcumin (individually or combination) indicates higher potency of the combination to induce apoptosis. For the first time, this study provides compelling evidence of the pharmacodynamic additive effect of limonoids and curcumin in inhibiting human colon cancer cells. The above results were also confirmed by fluorescence microscopy of SW480 cells treated with limonoids, curcumin and combination, after tagging with fluorescent probes. These results suggest that consumption of curcumin and limonoids together may offer greater protection against colon cancer.

Immunotoxicity of ochratoxin A and aflatoxin B1 in combination is associated with the nuclear factor kappa B signaling pathway in 3D4/21 cells.

PubMed

Hou, Lili; Gan, Fang; Zhou, Xuan; Zhou, Yajiao; Qian, Gang; Liu, Zixuan; Huang, Kehe

2018-05-01

The co-contamination of cereals, grains, crops, and animal feeds by mycotoxins is a universal problem. Humans and animals are exposed to several mycotoxins simultaneously as evidenced by extensive studies on this topic. Yet, most studies have addressed the effects of mycotoxins individually. Aflatoxin B1 and ochratoxin A can induce immunotoxicity. However, it remains unclear whether a combination of these mycotoxins aggravates immunotoxicity and the potential mechanism underlying this effect. In this study, we used the cell line 3D4/21, swine alveolus macrophages and innate immune cell. The results showed that the percentage of cell inhibition, annexin V/PI-positive rates, and the expression of pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-6) significantly increased and the release of lactate dehydrogenase and phagocytotic index were significantly decreased at different concentrations of aflatoxin B1 and ochratoxin A combination when compared with control. The combination of aflatoxin B1 and ochratoxin A significantly decreased the production of GSH and increased reactive oxygen species level. However, N-acetylcysteine suppressed the oxidative stress and alleviated the immunotoxicity induced by the combination. The combination of aflatoxin B1 and ochratoxin A markedly enhanced the degradation of IκBa, the phosphorylation of nuclear factor kappa B (p65), and the translocation of activated nuclear factor kappa B (NF-κB) into the nuclei as demonstrated by western blotting and confocal laser scanning microscopy. These effects could be reversed by BAY 11-7082, a specific inhibitor of NF-κB. Taken together, a combination of aflatoxin B1 and ochratoxin A could aggravate immunotoxicity by activating the NF-κB signaling pathway. Copyright © 2018 Elsevier Ltd. All rights reserved.

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

PubMed Central

Bai, Wenxia; Wang, Shudong; An, Shanshan; Guo, Mengjie; Gong, Guangming; Liu, Wenya; Ma, Shaoxin; Li, Xin; Fu, Jihua; Yao, Wenbing

2018-01-01

This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure. PMID:29643988

Barley responses to combined waterlogging and salinity stress: separating effects of oxygen deprivation and elemental toxicity

PubMed Central

Zeng, Fanrong; Shabala, Lana; Zhou, Meixue; Zhang, Guoping; Shabala, Sergey

2013-01-01

Salinity and waterlogging are two major factors affecting crop production around the world and often occur together (e.g., salt brought to the surface by rising water tables). While the physiological and molecular mechanisms of plant responses to each of these environmental constraints are studied in detail, the mechanisms underlying plant tolerance to their combined stress are much less understood. In this study, whole-plant physiological responses to individual/combined salinity and waterlogging stresses were studied using two barley varieties grown in either vermiculite (semi-hydroponics) or sandy loam. Two weeks of combined salinity and waterlogging treatment significantly decreased plant biomass, chlorophyll content, maximal quantum efficiency of PSII and water content (WC) in both varieties, while the percentage of chlorotic and necrotic leaves and leaf sap osmolality increased. The adverse effects of the combined stresses were much stronger in the waterlogging-sensitive variety Naso Nijo. Compared with salinity stress alone, the combined stress resulted in a 2-fold increase in leaf Na+, but a 40% decrease in leaf K+ content. Importantly, the effects of the combined stress were more pronounced in sandy loam compared with vermiculite and correlated with changes in the soil redox potential and accumulation of Mn and Fe in the waterlogged soils. It is concluded that hypoxia alone is not a major factor determining differential plant growth under adverse stress conditions, and that elemental toxicities resulting from changes in soil redox potential have a major impact on genotypic differences in plant physiological and agronomical responses. These results are further discussed in the context of plant breeding for waterlogging stress tolerance. PMID:23967003

[Changes in immunobiological reactivity under the combined action of microwave, infrasonic and gamma irradiation].

PubMed

Grigor'ev, Iu G; Batanov, G V; Stepanov, V S

1983-01-01

In experiments on rats and rabbits a study was made of the combined effect of 9.3 gHz and 0.1 gHz (200 and 1530 muW/cm2, respectively), infrasound (8 Hz, 115 db), and gamma-radiation (cumulative dose of 5.5 Gy) on cell and humoral immunity, and on autoimmune processes. It was shown that preirradiation with microwaves increased the resistance of the organism to gamma-radiation, and microwaves combined with infrasound enhanced the biological effect of gamma-radiation.

Efficacy of combined orthodontic-periodontic treatment for patients with periodontitis and its effect on inflammatory cytokines: A comparative study.

PubMed

Zhang, Jin; Zhang, Ai-Min; Zhang, Zong-Mei; Jia, Jin-Lin; Sui, Xin-Xin; Yu, Lu-Rui; Liu, Hai-Tao

2017-10-01

In this study, we aimed to investigate the efficacy of combined orthodontic-periodontic treatment in the treatment of patients with periodontitis and its effects on the levels of inflammatory cytokines. A total of 117 patients with periodontitis were randomly assigned to the basic group (receiving basic periodontic treatment, n = 58) and the combined group (receiving combined orthodontic-periodontic treatment, n = 59). In addition, 52 healthy people without periodontal disease were selected as the normal group. Probing depth, tooth mobility, plaque index, clinical attachment level, and sulcus bleeding index were recorded. ELISA was applied to detect gingival crevicular fluid (GCF) and serum levels of inflammatory cytokines. A 2-year clinical follow-up was conducted. Before treatment, the periodontal parameters (probing depth, tooth mobility, plaque index, clinical attachement level, and sulcus bleeding index) and GCF and serum levels of inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-1β, interleukin-5, interleukin-6, interleukin-8, tumor necrosis factor-α, and prostaglandin E2) in the combined and basic groups were higher than those in the normal group. After 6 and 18 months of treatment, the periodontal parameters and GCF and serum levels of inflammatory cytokines decreased in the combined and basic groups. The periodontal parameters and the GCF and serum levels of inflammatory cytokines in the combined group were significantly lower than those in the basic group after 18 months of treatment. The combined group had a lower recurrence rate compared with the basic group. Combined orthodontic-periodontic treatment had good clinical efficacy in the treatment of periodontitis and could effectively decrease the levels of inflammatory cytokines. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.

PubMed

Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Miyake, Masuyo; Li, Yunfeng; Nelson, Scott D; Dry, Sarah M; Bouvet, Michael; Elliott, Irmina A; Russell, Tara A; Singh, Arun S; Eckardt, Mark A; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

2017-11-28

The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm 3 : untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient.

Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by Combining Omega-3 Polyunsaturated Acid with Lyciumbarbarum Polysaccharide.

PubMed

Shi, Zhe; Wu, Di; Yao, Jian-Ping; Yao, Xiaoli; Huang, Zhijian; Li, Peng; Wan, Jian-Bo; He, Chengwei; Su, Huanxing

2016-01-13

Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons using an in vitro ischemic model. Our study demonstrated that treatment with docosahexaenoic acid (DHA), a major component of the ω-3 PUFAs family, significantly inhibited the increase of intracellular Ca(2+) in cultured wild type (WT) cortical neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival compared with the vehicle-treated control. The protective effects were further confirmed in cultured neurons with high endogenous ω-3 PUFAs that were isolated from fat-1 mice, in that a higher survival rate was found in fat-1 neurons compared with wild-type neurons after OGD/R injury. Our study also found that treatment with LBP (50 mg/L) activated Trk-B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis compared with the control. Notably, both combining LBP treatment with ω-3 PUFAs administration to WT neurons and adding LBP to fat-1 neurons showed enhanced effects on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium overload and neurotrophic pathway. The results of the study suggest that ω-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.

The combined effects of transcutaneous electrical nerve stimulation (TENS) and stretching on muscle hardness and pressure pain threshold.

PubMed

Karasuno, Hiroshi; Ogihara, Hisayoshi; Morishita, Katsuyuki; Yokoi, Yuka; Fujiwara, Takayuki; Ogoma, Yoshiro; Abe, Koji

2016-04-01

[Purpose] This study aimed to clarify the immediate effects of a combined transcutaneous electrical nerve stimulation and stretching protocol. [Subjects] Fifteen healthy young males volunteered to participate in this study. The inclusion criterion was a straight leg raising range of motion of less than 70 degrees. [Methods] Subjects performed two protocols: 1) stretching (S group) of the medial hamstrings, and 2) tanscutaneous electrical nerve stimulation (100 Hz) with stretching (TS group). The TS group included a 20-minute electrical stimulation period followed by 10 minutes of stretching. The S group performed 10 minutes of stretching. Muscle hardness, pressure pain threshold, and straight leg raising range of motion were analyzed to evaluate the effects. The data were collected before transcutaneous electrical nerve stimulation (T1), before stretching (T2), immediately after stretching (T3), and 10 minutes after stretching (T4). [Results] Combined transcutaneous electrical nerve stimulation and stretching had significantly beneficial effects on muscle hardness, pressure pain threshold, and straight leg raising range of motion at T2, T3, and T4 compared with T1. [Conclusion] These results support the belief that transcutaneous electrical nerve stimulation combined with stretching is effective in reducing pain and decreasing muscle hardness, thus increasing range of motion.

A combination of grapefruit seed extract and concentrated cranberry juice as a potential antimicrobial preservative for the improvement of microbiological stability of hypromellose gel.

PubMed

Bernatoniene, Jurga; Keraitė, Rasa; Masteiková, Ruta; Pavilonis, Alvydas; Savickas, Arūnas

2013-10-01

Aqueous hypromellose gels are not microbiologically stable - they show signs of microorganism growth during storage. To extend the shelf-life of the gels, antimicrobial preservatives are needed. Some substances of plant origin are known for their antimicrobial properties, and thus they may be used as an alternative to synthetic preservatives. Therefore, the aim of this study was to evaluate the microbiological stability of aqueous hypromellose gel and the effectiveness of natural substances - grapefruit seed extract (GSE), concentrated cranberry juice, and a combination thereof - on the antimicrobial protection of the gel. The evaluation of the antimicrobial activity of GSE and cranberry juice showed that their antimicrobial effects differed. Both cranberry juice and GSE inhibited the growth of the standard gram-positive and gram-negative bacteria, but the effect of GSE was significantly stronger. Candida albicans was sensitive only to GSE. For this reason, in order to affect all the microorganisms studied, either a combination of 0.7% GSE and 10% cranberry juice, or 5% GSE alone may be used. The combination of GSE and cranberry juice was effective only in acidic medium (pH being 2.5-5), while the antimicrobial effect of GSE was not dependent on the pH value.

Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines.

PubMed

García-López, Patricia; Rodríguez-Dorantes, Mauricio; Pérez-Cárdenas, Enrique; Cerbón, Marco; Mohar-Betancourt, Alejandro

2004-06-01

We investigated the ability of the novel pure antiestrogen ICI 182,780 to modulate the cytotoxic effects of cisplatin in several cervical cancer cell lines. The effect of cisplatin alone and cisplatin combined with ICI 182,780 on cellular death was studied using an assay based on a tetrazolium dye (sodium 3'-[1-(phenylamino-carbonyl)-3,4-tetrazolium], XTT). Before and after treatment with ICI 182,780, expression of the estrogen and progesterone receptor genes were assessed by a reverse transcriptase polymerase chain reaction (RT-PCR). Cell-cycle modifications after combined treatment with cisplatin and ICI 182,780 were studied by flow cytometry. Analysis of the data by the isobologram method showed that the combination of ICI 182,780 and cisplatin produced a synergistic antiproliferative effect in cervical cancer cells. The effect of ICI 182,780 on the cytotoxicity of cisplatin could be mediated, at least partially, by inhibition of estrogen and progesterone gene expression and by arresting the cell cycle at the G(2)/M phase. Our results suggest that ICI 182,780 can improve the efficacy of cisplatin in cancer cells and that this antihormonal drug therapy may be a useful candidate for further evaluation in combination with antineoplastic drugs, particularly cisplatin, in the treatment of cancer.

Combined effects of methamphetamine and zolpidem on performance and mood during simulated night shift work.

PubMed

Hart, Carl L; Haney, Margaret; Nasser, Jennifer; Foltin, Richard W

2005-07-01

Individuals who work irregular or rotating shifts often use stimulants and sedatives to offset shift-change-related mood and performance decrements. During this simulated shift work study the acute effects of the stimulant, methamphetamine were examined, and the effects of the hypnotic, zolpidem, and the combination were assessed during the shift after drug administration. Eight volunteers completed this 21-day, within-participant, residential laboratory study during which they received a single oral methamphetamine dose (0 or 10 mg) 1 h after waking, i.e., before task performance, and a single oral zolpidem dose (0 or 10 mg) 1 h before bedtime under 2 shift conditions: day shift and night shift. When participants received placebo at both dosing times, performance on some psychomotor tasks (e.g., the digit-symbol substitution task) and on some measures of mood (e.g., ratings of "Energetic") were disrupted during the night shift, relative to the day shift. Methamphetamine alone eliminated virtually all shift-related disruptions, while zolpidem alone and the drug combination produced few effects. These data indicate that shift changes produce performance impairments and mood alterations that are improved by a single low to moderate dose of methamphetamine. Zolpidem, given alone or in combination with methamphetamine, did not alleviate most shift-change mood and performance effects.

Fisetin enhances chemotherapeutic effect of cabazitaxel against human prostate cancer cells

PubMed Central

Mukhtar, Eiman; Adhami, Vaqar Mustafa; Siddiqui, Imtiaz Ahmad; Verma, Ajit Kumar; Mukhtar, Hasan

2016-01-01

Although treatment of prostate cancer (PCa) has improved over the past several years, taxanes such as cabazitaxel remain the only form of effective chemotherapy that improves survival in patients with metastatic castration-resistant PCa. However, the effectiveness of this class of drugs has been associated with various side effects and drug resistance. We previously reported that fisetin, a hydroxyflavone, is a microtubule stabilizing agent and inhibits PCa cell proliferation, migration, and invasion and suggested its use as an adjuvant for treatment of prostate and other cancer types. In this study, we investigated the effect of fisetin in combination with cabazitaxel with the objective to achieve maximum therapeutic benefit, reduce dose and toxicity and minimize or delay the induction of drug resistance and metastasis. Our data show for the first time that a combination of fisetin (20 μM) enhances cabazitaxel (5nM) and synergistically reduces 22Rν1, PC-3M-luc-6, and C4-2 cell viability and metastatic properties with minimal adverse effects on normal prostate epithelial cells. In addition, the combination of fisetin with cabazitaxel was associated with inhibition of proliferation and enhancement of apoptosis. Furthermore, combination treatment resulted in inhibition of tumor growth, invasion and metastasis when assessed in two in-vivo xenograft mouse models. These results provide evidence that fisetin may have therapeutic benefit for patients with advanced PCa through enhancing the efficacy of cabazitaxel under both androgen-dependent and androgen-independent conditions. This study underscores the benefit of the combination of fisetin with cabazitaxel for the treatment of advanced and resistant PCa and possibly other cancer types. PMID:27765854

Effect of the combination of metformin hydrochloride and melatonin on oxidative stress before and during pregnancy, and biochemical and histopathological analysis of the livers of rats after treatment for polycystic ovary syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemos, Ana Janaina Jeanine M.; Unit of Medical and Health Sciences, Universidade Federal de Campina Grande; Peixoto, Christina A.

The aim of the present study was to analyze the effect of a combination of metformin hydrochloride and melatonin on oxidative stress together with a biochemical and histopathological analysis of the livers of Wistar rats induced with PCOS. The results indicated that a combination of the drugs was more effective in the reduction of plasmatic levels of liver enzyme alanine aminotransferase, nitric oxide and total glutathione, and decreased the inflammatory response and histopathological damage, producing results that were significantly similar to animals from the control group. A mixture of the drugs produced more effective results against liver toxicity caused bymore » PCOS, encouraging the normalization of biochemical parameters. During pregnancy, there was reduced oxidative stress compared to monotherapeutic use of these drugs. Interestingly, the combination of the drugs caused a physiological reaction similar to responses identified in healthy rats without induction of the PCOS control group. However, the clinical and physiological effectiveness of the combination should be further explored, especially with respect to the possible side effects on offspring. - Highlights: • Studies have documented increased oxidative stress in patients with PCOS. • It has been noted that women with PCOS have a high prevalence of liver alterations. • Liver disease in pregnancy may be pre-existing increasing the newborn mortality. • Metformin/melatonin associated reduced oxidative stress in liver in pregnant rats. • Association of metformin/melatonin normalizes hepatic biochemical parameters.« less

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Management of Varicose Veins and Chronic Venous Insufficiency in a Comparative Registry with Nine Venoactive Products in Comparison with Stockings.

PubMed

Belcaro, G; Dugall, M; Luzzi, R; Corsi, M; Ledda, A; Ricci, A; Pellegrini, L; Cesarone, M R; Hosoi, M; Errichi, B M; Cornelli, U; Cotellese, R; Agus, G; Feragalli, B

2017-09-01

The aim of this registry study was to compare products used to control symptoms of CVI. Endpoints of the study were microcirculation, effects on volume changes, and symptoms (analogue scale). Pycnogenol, venoruton, troxerutin, the complex diosmin-hesperidin, Antistax, Mirtoselect (bilberry), escin, and the combination Venoruton-Pycnogenol (VE-PY) were compared with compressions. No safety or tolerability problems were observed. At inclusion, measurements in the groups were comparable: 1,051 patients completed the registry. Best performers : Venoruton, Pycnogenol, and the combination VE-PY produced the best effects on skin flux. These products and the combination VE-PY better improved PO 2 and PCO 2 . The edema score was decreased more effectively with the combination and with Pycnogenol. Venoruton; Antistax also had good results. Considering volumetry, the best performers were the combination PY-VE and the two single products Venoruton and Pycnogenol. Antistax results for edema were also good. The best improvement in symptoms score were obtained with Pycnogenol and compression. A larger decrease in oxidative stress was observed with Pycnogenol, Venoruton, and with the VE-PY combination. Good effects of Antistax were also observed. Parestesias were lower with Pycnogenol and with Antistax. Considering the need for interventions, the best performers were Pycnogenol, VE-PY, and compression. The efficacy of Pycnogenol and the combination are competitive with stockings that do not have the same tolerability in warmer climates. A larger and more prolonged evaluation is suggested to evaluate cost-efficacy (and non-interference with drugs) of these products in the management of CVI. The registry is in progress; other products are in evaluation.

A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia.

PubMed

Jenkins, David J A; Kendall, Cyril W C; Faulkner, Dorothea; Vidgen, Edward; Trautwein, Elke A; Parker, Tina L; Marchie, Augustine; Koumbridis, George; Lapsley, Karen G; Josse, Robert G; Leiter, Lawrence A; Connelly, Philip W

2002-12-01

Plant sterols, soy proteins, and viscous fibers are advised for cholesterol reduction but their combined effect has never been tested. We therefore assessed their combined effect on blood lipids in hyperlipidemic subjects who were already consuming a low-saturated fat, low-cholesterol diet before starting the study. The test (combination) diet was 1 month in duration and was very low in saturated fat and high in plant sterols (1 g/1,000 kcal), soy protein (23 g/1,000 kcal), and viscous fibers (9 g/1,000 kcal) obtained from foods available in supermarkets and health food stores. One subject also completed 2 further diet periods: a low-fat control diet and a control diet plus 20 mg/d lovastatin. Fasting blood lipids, blood pressure, and body weight were measured prior to and at weekly intervals during the study. The combination diet was rated as acceptable and very filling. The diet reduced low-density lipoprotein (LDL)-cholesterol by 29.0% +/- 2.7% (P <.001) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol by 26.5% +/- 3.4% (P <.001). Near maximal reductions were seen by week 2. In the subject who took Mevacor and control diets each for 4 weeks, the reduction in LDL:HDL-cholesterol on Mevacor was similar to the combination diet. We conclude that acceptable diets of foods from supermarkets and health food stores that contain recognized cholesterol-lowering dietary components in combination (a dietary portfolio) may be as effective as the starting dose of older first-line drugs in managing hypercholesterolemia. Copyright 2002, Elsevier Science (USA). All rights reserved.

Combination therapy with andrographolide and D-penicillamine enhanced therapeutic advantage over monotherapy with D-penicillamine in attenuating fibrogenic response and cell death in the periportal zone of liver in rats during copper toxicosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, Dijendra Nath; Sen, Gargi; Chowdhury, Kaustav Dutta

2011-01-01

Long treatment regime with D-penicillamine is needed before it can exert clinically meaningful benefits in the treatment of copper toxicosis. The consequence of long-term D-penicillamine treatment is associated with numerous side effects. The limitations of D-penicillamine monotherapy prompted us to search for more effective treatment strategies that could decrease the duration of D-penicillamine therapy. The present study was designed to evaluate the therapeutic potential of D-penicillamine in combination with another hepatoprotective drug, andrographolide in treatment of copper toxicosis in rats. D-penicillamine treatment led to the excretion of copper through urine. Addition of andrographolide to D-penicillamine regime appeared to increase protectionmore » of liver by increasing the biliary excretion of copper and reduction in cholestatic injury. The early removal of the causative agent copper during combination treatment was the most effective therapeutic intervention that contributed to the early rectification of fibrosis in liver. Combination treatment reduced Kupffer cells accumulation and TNF{alpha} production in liver of copper exposed rats. In particular, andrographolide mediated the anti-inflammatory effect by inhibiting the cytokine production. However, another possible mechanism of cytoprotection of andrographolide was decreasing mitochondrial production of superoxide anions that resulted in better restoration of mitochondrial dysfunction during combination therapy than monotherapy. Furthermore, ROS inhibition by combination regimen resulted in significant decline in activation of caspase cascade. Inhibition of caspases attenuated apoptosis of hepatocytes, induced by chronic copper exposure. In summary, this study suggested that added benefit of combination treatment over use of either agent alone in alleviating the hepatotoxicity and fibrosis associated with copper toxicosis.« less

Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities.

PubMed

Yoshiji, Hitoshi; Kuriyama, Shigeki; Noguchi, Ryuichi; Yoshii, Junichi; Ikenaka, Yasuhide; Yanase, Koji; Namisaki, Tadashi; Kitade, Mitsuteru; Yamazaki, Masaharu; Akahane, Takemi; Asada, Kiyoshi; Tsujimoto, Tatsuhito; Uemura, Masahito; Fukui, Hiroshi

2006-01-01

Recent studies have revealed that angiogenesis plays a pivotal role in carcinogenesis and tumor growth. We previously reported that the clinically used vitamin K(2) (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exerted potent anti-angiogenic activities. The aim of our current study was to examine the combination effect of VK and ACE-I on hepatocarcinogenesis induced by diethyl-nitrosamine, and orthotopic hepatocellular carcinoma (HCC) growth in rats. When used individually, both VK and ACE-I at clinically comparable low doses exerted significant inhibitory effects on tumor development in the liver. A combination treatment of VK and ACE-I showed a more potent suppressive effect against hepatocarcinogenesis. Neovascularization increased during hepatocarcinogenesis, and VK and ACE-I significantly attenuated angiogenesis in the tumor. In orthotopic HCC transplantation, VK and ACE-I also showed marked suppressive effects against HCC development similar to those against hepatocarcinogenesis. In both experiments, the suppressive effects of VK and ACE-I against angiogenesis were similar in magnitude to their inhibitory effects against hepatocarcinogenesis and orthotopic HCC development. In the orthotopic model, VK and ACE-I treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. Since both VK and ACE-I are widely used in clinical practice without serious side effects, this combination therapy may be an effective new therapeutic strategy against hepatocarcinogenesis and HCC growth in the future.

Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination.

PubMed

Hysek, Cédric M; Simmler, Linda D; Schillinger, Nathalie; Meyer, Nicole; Schmid, Yasmin; Donzelli, Massimiliano; Grouzmann, Eric; Liechti, Matthias E

2014-03-01

Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125 mg of MDMA increased positive mood more than 60 mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).

A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study.

PubMed

Kant, S B; van den Kerckhove, E; Colla, C; Tuinder, S; van der Hulst, R R W J; Piatkowski de Grzymala, A A

2018-01-01

Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars. Fifty-eight patients with hypertrophic scars ( n  = 31) and keloid scars ( n  = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly ( P  < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3-4 months, 4-6 months, and >12 months after start of therapy in both keloids and hypertrophic scars. This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.Level of evidence: Level IV, therapeutic study.

Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body-weight reduction and glucose homeostasis of obese rats fed a cafeteria diet.

PubMed

Vickers, Steven P; Cheetham, Sharon C; Headland, Katie R; Dickinson, Keith; Grempler, Rolf; Mayoux, Eric; Mark, Michael; Klein, Thomas

2014-01-01

The present study assessed the potential of the sodium glucose-linked transporter (SGLT)-2 inhibitor empagliflozin to decrease body weight when administered alone or in combination with the clinically effective weight-loss agents orlistat and sibutramine in obese rats fed a cafeteria diet. Female Wistar rats were exposed to a cafeteria diet to induce obesity. Empagliflozin was dosed once daily (10, 30, and 60 mg/kg) for 28 days. Combination studies were subsequently performed using a submaximal empagliflozin dose (10 mg/kg) with either sibutramine or orlistat. Body weight, food, and water intake were recorded daily. The effect of drug treatment on glucose tolerance, relevant plasma parameters, and carcass composition was determined. Empagliflozin dose-dependently reduced body weight, plasma leptin, and body fat though increased urinary glucose excretion. The combination of empagliflozin and orlistat significantly reduced body weight compared to animals treated with either drug alone, and significantly improved glucose tolerance, plasma insulin, and leptin compared to vehicle-treated controls. The effect of sibutramine to improve glycemic control in an oral glucose-tolerance test was also significantly increased, with empagliflozin and combination treatment leading to a reduction in carcass fat greater than that observed with either drug alone. These data demonstrate that empagliflozin reduces body weight in cafeteria-fed obese rats. In combination studies, empagliflozin further improved the body-weight or body-fat loss of animals in comparison to orlistat or sibutramine alone. Such studies may indicate improved strategies for the treatment of obese patients with prediabetes or type 2 diabetes.

Randomized trial of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) on symptoms of benign prostatic hyperplasia (BPH).

PubMed

Preuss, H G; Marcusen, C; Regan, J; Klimberg, I W; Welebir, T A; Jones, W A

2001-01-01

Because benign prostatic hyperplasia (BPH) is relatively common, it is important to discover safe and effective means to treat this often debilitating perturbation. Accordingly, we examined the effectiveness of a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) in treating symptoms of BPH. We undertook a randomized, placebo-controlled, double-blind study. Patients were enrolled from 3 urological practices in the USA. 144 subjects were randomized for study. 17 subjects eventually withdrew, leaving 70 patients in the test group and 57 in the placebo group to complete the study. Inclusion criteria consisted of a diagnosis of BPH, no evidence of cancer, and a maximal urinary flow rate between 5 and 15 ml/second. Patients received either placebo or the combined natural products for 3 months. Evaluations were performed via the American Urological Association (AUA) Symptom Index score, urinary flow rate, PSA measurement, and residual bladder volume. Nocturia showed a markedly significant decrease in severity in patients receiving the combined natural products compared to those taking placebo (p < 0.001). Daytime frequency was also lessened significantly (p < 0.04). When the average individual total AUA Symptom Index score in the test group was compared to that in the placebo group at the end of the study, the difference proved highly significant (p < 0.014). PSA measurements, maximal and average urinary flow rates, and residual volumes showed no statistically significant differences. When taken for 3 months, a combination of natural products (cernitin, saw palmetto, B-sitosterol, vitamin E) compared to placebo can significantly lessen nocturia and frequency and diminish overall symptomatology of BPH as indicated by an improvement in the total AUA Symptom Index score. The combination of natural products caused no significant adverse side effects.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Social Competence Intervention in Autistic Spectrum Disorders (ASDS) - A Case Study

ERIC Educational Resources Information Center

Amin, Noor A.; Oweini, Ahmad

2013-01-01

The purpose of this case study was to determine the effectiveness of a combined intervention in remediating the social skills in a first-grader with a disorder from the autism spectrum disorders (ASDs). The researcher also aimed to identify the changes observed during the intervention period. The combined intervention consisted of reading…

Effects of combining vertical and horizontal information into a primary flight display

NASA Technical Reports Server (NTRS)

Abbott, Terence S.; Nataupsky, Mark; Steinmetz, George G.

1987-01-01

A ground-based aircraft simulation study was conducted to determine the effects of combining vertical and horizontal flight information into a single display. Two display configurations were used in this study. The first configuration consisted of a Primary Flight Display (PFD) format and a Horizontal Situation Display (HSD) with the PFD displayed conventionally above the HSD. For the second display configuration, the HSD format was combined with the PFD format. Four subjects participated in this study. Data were collected on performance parameters, pilot-control inputs, auditory evoked response parameters (AEP), oculometer measurements (eye-scan), and heart rate. Subjective pilot opinion was gathered through questionnaire data and scorings for both the Subjective Workload Assessment Technique (SWAT) and the NASA Task Load Index (NASA-TLX). The results of this study showed that, from a performance and subjective standpoint, the combined configuration was better than the separate configuration. Additionally, both the eye-transition and eye-dwell times for the separate HSD were notably higher than expected, with a 46% increase in available visual time when going from double to single display configuration.

Combination could be another tool for bowel preparation?

PubMed Central

Soh, Jae Seung; Kim, Kyung-Jo

2016-01-01

Optimal bowel preparation increases the cecal intubation rate and detection of neoplastic lesions while decreasing the procedural time and procedural-related complications. Although high-volume polyethylene glycol (PEG) solution is the most frequently used preparation for bowel cleansing, patients are often unwilling to take PEG solution due to its large volume, poor palatability, and high incidence of adverse events, such as abdominal bloating and nausea. Other purgatives include osmotic agents (e.g., sodium phosphate, magnesium citrate, and sodium sulfate), stimulant agents (e.g., senna, bisacodyl, and sodium picosulfate), and prokinetic agents (e.g., cisapride, mosapride, and itopride). A combination of PEG with an osmotic, stimulant, or prokinetic agent could effectively reduce the PEG solution volume and increase patients’ adherence. Some such solutions have been found in several published studies to not be inferior to PEG alone in terms of bowel cleansing quality. Although combination methods showed similar efficacy and safety, the value of these studies is limited by shortcomings in study design. New effective and well-tolerated combination preparations are required, in addition to rigorous new validated studies. PMID:26973388

The Impact of Web Page Text-Background Colour Combinations on Readability, Retention, Aesthetics and Behavioural Intention

ERIC Educational Resources Information Center

Hall, Richard H.; Hanna, Patrick

2004-01-01

The purpose of this experiment was to examine the effect of web page text/background colour combination on readability, retention, aesthetics, and behavioural intention. One hundred and thirty-six participants studied two Web pages, one with educational content and one with commercial content, in one of four colour-combination conditions. Major…

Cranberry Juice and Combinations of Its Organic Acids Are Effective against Experimental Urinary Tract Infection

PubMed Central

Jensen, Heidi D.; Struve, Carsten; Christensen, Søren B.; Krogfelt, Karen A.

2017-01-01

The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced (P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together (P < 0.001), and so did the combination of malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents. PMID:28421045

Rail base corrosion and cracking prevention

DOT National Transportation Integrated Search

2014-07-01

Rail base corrosion combined with fatigue or damage can significantly reduce rail life. Studies were done to examine the relative contribution of damage, corrosion, and fatigue on rail life. The combined effects can be separated into constituent fact...

Effects of Transcranial Direct Current Stimulation, Transcranial Pulsed Current Stimulation, and Their Combination on Brain Oscillations in Patients with Chronic Visceral Pain: A Pilot Crossover Randomized Controlled Study.

PubMed

Thibaut, Aurore; Russo, Cristina; Hurtado-Puerto, Aura Maria; Morales-Quezada, Jorge Leon; Deitos, Alícia; Petrozza, John Christopher; Freedman, Steven; Fregni, Felipe

2017-01-01

Chronic visceral pain (CVP) syndromes are persistently painful disorders with a remarkable lack of effective treatment options. This study aimed at evaluating the effects of different neuromodulation techniques in patients with CVP on cortical activity, through electreocephalography (EEG) and on pain perception, through clinical tests. A pilot crossover randomized controlled study. Out-patient. Adults with CVP (>3 months). Participants received four interventions in a randomized order: (1) transcranial pulsed current stimulation (tPCS) and active transcranial direct current stimulation (tDCS) combined, (2) tPCS alone, (3) tDCS alone, and (4) sham condition. Resting state quantitative electroencephalography (qEEG) and pain assessments were performed before and after each intervention. Results were compared with a cohort of 47 healthy controls. We enrolled six patients with CVP for a total of 21 visits completed. Compared with healthy participants, patients with CVP showed altered cortical activity characterized by increased power in theta, alpha and beta bands, and a significant reduction in the alpha/beta ratio. Regarding tES, the combination of tDCS with tPCS had no effect on power in any of the bandwidths, nor brain regions. Comparing tPCS with tDCS alone, we found that tPCS induced higher increase in power within the theta and alpha bandwidths. This study confirms that patients with CVP present abnormal EEG-indexed cortical activity compared with healthy controls. Moreover, we showed that combining two types of neurostimulation techniques had no effect, whereas the two interventions, when applied individually, have different neural signatures.

Effect of a Combined Tai Chi, Resistance Training and Dietary Intervention on Cognitive Function in Obese Older Women.

PubMed

Xu, F; Delmonico, M J; Lofgren, I E; Uy, K M; Maris, S A; Quintanilla, D; Taetzsch, A G; Letendre, J; Mahler, L

2017-01-01

Cognitive decline in older adults is a major public health problem and can compromise independence and quality of life. Exercise and diet have been studied independently and have shown to be beneficial for cognitive function, however, a combined Tai Chi, resistance training, and diet intervention and its influence on cognitive function has not been undertaken. The current study used a 12-week non-randomized research design with experiment and control groups to examine the effect of a combined Tai Chi, resistance training, and diet intervention on cognitive function in 25 older obese women. Results revealed improvements in domain specific cognitive function in our sample. Baseline cognitive function was correlated with changes in dietary quality. These findings suggest that Tai Chi and resistance training combined with diet intervention might be beneficial for community-based programs aiming to improve cognitive function.

Effect of Passive, Active and Combined Warm up on Lower Limb Muscle Performance and Dynamic Stability in Recreational Sports Players.

PubMed

Gogte, Kedar; Srivastav, Prateek; Miyaru, Ganesh Balthillaya

2017-03-01

Warm up is an activity that is done before a sports activity. The warm up can be done actively and passively. The preferred mode is active warm up in athletes. There are inconclusive effects of passive warm up compared with an active warm up on short term muscle performance. The cumulative effect of passive and active warm up on muscle performance and dynamic stability is not known. To find out the effects of passive, active and combined warm up on lower limb muscle performance and dynamic stability in recreational sports players. A randomized crossover study was done on 19 recreational lower limb dominant sports players. Three different warm ups were included in the study passive, active and combined. Active warm up included series of activities like cycling, leg press, jump squats, squat jumps while passive warm up included application of moist heat for a period of 20 minutes on lower limb muscles. Combined warm up included both passive and active warm up. Six different sequences were made from these three warm ups. Subjects were screened and allotted into different groups based on the six warm up sequences after sequence randomization with 48 hours wash out period. After every warm up session Vertical Jump Test (VJT) and Star Excursion Balance Test (SEBT) was performed and results were recorded. Study duration was one year and six months. There was no difference noticed in both the outcome measures. Mean and SD values for passive, active and combined warm up are 47.62±9.64, 48.50±10.16 and 48.87±10.70 respectively in Vertical Jump Test (VJT) and 85.43±8.61, 85.17±8.60 and 85.17±8.38 respectively for SEBT. The p-value for mean difference between passive-active, active-combined, combined-passive are 0.67, 1.00, 0.51 respectively, for VJT and 1.00, 1.00, 1.00 respectively for SEBT. All warm ups are equally effective in short term sports performance.

Effect of Passive, Active and Combined Warm up on Lower Limb Muscle Performance and Dynamic Stability in Recreational Sports Players

PubMed Central

Gogte, Kedar; Miyaru, Ganesh Balthillaya

2017-01-01

Introduction Warm up is an activity that is done before a sports activity. The warm up can be done actively and passively. The preferred mode is active warm up in athletes. There are inconclusive effects of passive warm up compared with an active warm up on short term muscle performance. The cumulative effect of passive and active warm up on muscle performance and dynamic stability is not known. Aim To find out the effects of passive, active and combined warm up on lower limb muscle performance and dynamic stability in recreational sports players. Materials and Methods A randomized crossover study was done on 19 recreational lower limb dominant sports players. Three different warm ups were included in the study passive, active and combined. Active warm up included series of activities like cycling, leg press, jump squats, squat jumps while passive warm up included application of moist heat for a period of 20 minutes on lower limb muscles. Combined warm up included both passive and active warm up. Six different sequences were made from these three warm ups. Subjects were screened and allotted into different groups based on the six warm up sequences after sequence randomization with 48 hours wash out period. After every warm up session Vertical Jump Test (VJT) and Star Excursion Balance Test (SEBT) was performed and results were recorded. Study duration was one year and six months. Results There was no difference noticed in both the outcome measures. Mean and SD values for passive, active and combined warm up are 47.62±9.64, 48.50±10.16 and 48.87±10.70 respectively in Vertical Jump Test (VJT) and 85.43±8.61, 85.17±8.60 and 85.17±8.38 respectively for SEBT. The p-value for mean difference between passive-active, active-combined, combined-passive are 0.67, 1.00, 0.51 respectively, for VJT and 1.00, 1.00, 1.00 respectively for SEBT. Conclusion All warm ups are equally effective in short term sports performance. PMID:28511496

Osteoprotective effect of combination therapy of low-dose oestradiol with G15, a specific antagonist of GPR30/GPER in ovariectomy-induced osteoporotic rats.

PubMed

Kang, Wen-Bo; Cong, Yu; Ru, Jiang-Ying; Ying, Si-Qi; Zhu, Ting; Wang, Dong-Sheng; Liu, Xiao-Wei; Liu, Gang; Zhao, Jian-Ning

2015-07-03

Identified and cloned in 1996 for the first time, G protein-coupled oestrogen receptor (ER) 30 (GPR30/GPER) has been a hot spot in the field of sex hormone research till now. In the present study, we examined the effects of low-dose oestradiol (E2) combined with G15, a specific antagonist of GPR30 on ovariectomy (OVX)-induced osteoporosis in rats. Female Sprague-Dawley (SD) rats undergoing OVX were used to evaluate the osteoprotective effect of the drugs. Administration of E2 [35 μg/kg, intraperitoneally (ip), three times/week) combining G15 (160 μg/kg, ip, three times/week) for 6 weeks was found to have prevented OVX-induced effects, including increase in bone turnover rate, decrease in bone mineral content (BMC) and bone mineral density (BMD), damage of bone structure and the aggravation in biomechanical properties of bone. The therapeutic effect of these two drugs in combination was better than that of E2 alone. Meanwhile, the administration of G15 prevented body weight increase or endometrium proliferation in the rats. In conclusion, administration of low-dose E2 combining G15 had a satisfactory bone protective effect for OVX rats, without significant influence on body weight or the uterus. This combination therapy may be an effective supplement of drugs in prevention and treatment for postmenopausal osteoporosis. © 2015 Authors.

Synergistic Cytotoxicity Effect by Combination Treatment of Polyketide Derivatives from Annona muricata Linn Leaves and Doxorubicin as Potential Anticancer Material on Raji Cell Line

NASA Astrophysics Data System (ADS)

Artanti, A. N.; Astirin, O. P.; Prayito, A.; Fisma, R.; Prihapsara, F.

2018-03-01

Nasopharynx cancer is one of the most deadly cancer. The main priority of nasopharynx cancer treatment is the use of chemotherapeutic agents, especially doxorubicin. However, doxorubicin might also lead to diverse side effect. An approach recently develop to overcome side effect of doxorubicin is to used of combined chemotherapeutic agent. One of the compounds found effication as an anticancer agent on nasopharynx cancer is acetogenin, a polyketide compound that is abundant in Annona muricata L. leaves. This study has been done to examine polyketide derivatives was isolated from Annona muricata L. which has potency to induce apoptosis by p53 expression on raji cell line. The determination of cytotoxic combination activity from polyketide derivative and doxorubicin was evaluated using MTT assay to obtain the value of CI (combination index). Data analysis showed that combination of polyketide derivative from Annona muricata L. (14,4 µg/ml) and doxorubicin with all of concentration performed synergistic effect on raji cell line with CI value from 0.13 – 0.65.

Synergistic Cytotoxicity of Bendamustine and the BTK Inhibitor in a Mantle Cell Lymphoma Cell Line.

PubMed

Hagiwara, Kazumi; Tokunaga, Takashi; Iida, Hiroatsu; Nagai, Hirokazu

2015-12-01

Bendamustine is effective in B-cell malignancies, including mantle cell lymphoma (MCL), alone and in combination with other agents. This study investigated the combination effect of bendamustine and the Bruton tyrosine kinase (BTK) inhibitor PCI-32765 on MCL cell death and the underlying mechanisms. Cytotoxicity was examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MIT) assay. Apoptosis was assessed by annexin V/propidium iodide staining and protein expression was analyzed by western blotting. When combined with bendamustine, PCI-32765 showed a synergistic effect on growth inhibition of the MCL cell line Jeko-1. Cleavage of caspase-3 and poly-(ADP-ribose) polymerase was increased, indicating enhanced apoptosis induction. In addition, this combination decreased the protein expression of cyclin D1. Phosphorylated v-akt murine thymoma viral oncogene homolog 1 (AKT) (Ser473) was also down-regulated, suggesting a suppression of the phosphatidylinositol 3-kinase/AKT signaling pathway. Combination treatment with bendamustine and a BTK inhibitor may be effective in MCL therapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer

PubMed Central

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents – liposomal apigenin and tyroservatide – was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer. PMID:28761344

Synergistic apoptotic effects of apigenin TPGS liposomes and tyroservatide: implications for effective treatment of lung cancer.

PubMed

Jin, Xin; Yang, Qing; Zhang, Youwen

2017-01-01

To develop an alternative treatment for lung cancer, a combination of two potent chemotherapeutic agents - liposomal apigenin and tyroservatide - was developed. The therapeutic potential of this combination was investigated using A549 cells. Apigenin and tocopherol derivative-containing D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) liposomes might improve the delivery of apigenin to tumor cells, both in vitro and in vivo. Importantly, compared to either agent alone, the combination of apigenin TPGS liposomes and tyroservatide exhibited superior cytotoxicity, induced stronger G2 arrest, and suppressed A549 cancer cell invasion at a lower dose. The proapoptotic synergistic effects were also observed in A549 cells using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, flow cytometry, and Western blot analysis. More importantly, in vivo results showed that the combination of apigenin TPGS liposomes and tyroservatide exhibited tumor-growth inhibitory effects in A549 cell-bearing mice. In conclusion, our study showed that this combination therapy could serve as a promising synergistic therapeutic approach to improve outcomes in patients with lung cancer.

Effects of high-energy shock waves combined with biological response modifiers or Adriamycin on a human kidney cancer xenograft.

PubMed

Oosterhof, G O; Smiths, G A; deRuyter, J E; Schalken, J A; Debruyne, F M

1990-01-01

We have studied the effect of high-energy shock waves (HESW) alone or in combination with biological response modifiers (BRMs) or Adriamycin on the growth of the NU-1 human kidney cancer xenograft. When HESW are administered repeatedly (four sessions of 800 shock waves on days 0, 2, 4 and 6) a prolonged delay in tumor growth was found compared with that following a single administration. This effect was temporary, and several days after stopping the HESW administration the tumor regained its original growth potential (same doubling time). Tumor growth was suppressed for a longer period by the combination of 4 sessions of HESW and a single administration of Adriamycin, 5 mg/kg. Combination of HESW treatment with interferon alpha (5.0 ng/g body weight, three times/week) and tumor necrosis factor alpha (500 ng/g body weight, 5 days/week) s.c. around the tumor resulted in a complete cessation of tumor growth. While Adriamycin had an additive effect on HESW treatment, the combination with BRMs was highly synergistic.

Electroencephalographic study of chlorpromazine alone or combined with alpha-lipoic acid in a model of schizophrenia induced by ketamine in rats.

PubMed

Sampaio, Luis Rafael Leite; Borges, Lucas Teixeira Nunes; Barbosa, Talita Matias; Matos, Natalia Castelo Branco; Lima, Ricardo de Freitas; Oliveira, Mariana Nascimento de; Gularte, Viviane Nóbrega; Patrocínio, Manoel Cláudio Azevedo; Macêdo, Danielle; Vale, Otoni Cardoso do; Vasconcelos, Silvânia Maria Mendes de

2017-03-01

Schizophrenia is characterized by behavioral symptoms, brain function impairments and electroencephalographic (EEG) changes. Dysregulation of immune responses and oxidative imbalance underpins this mental disorder. The present study aimed to investigate the effects of the typical antipsychotic chlorpromazine (CP) alone or combined with the natural antioxidant alpha-lipoic acid (ALA) on changes in the hippocampal average spectral power induced by ketamine (KET). Three days after stereotactic implantation of electrodes, male Wistar rats were divided into groups treated for 10 days with saline (control) or KET (10 mg/kg, IP). CP (1 or 5 mg/kg, IP) alone or combined with ALA (100 mg/kg, P.O.) was administered 30 min before KET or saline. Hippocampal EEG recordings were taken on the 1st, 5th and 10th days of treatment immediately after the last drug administration. KET significantly increased average spectral power of delta and gamma-high bands on the 5th and 10th days of treatment when compared to control. Gamma low-band significantly increased on the 1st, 5th and 10th days when compared to control group. This effect of KET was prevented by CP alone or combined with ALA. Indeed, the combination of ALA 100 + CP1 potentiated the inhibitory effects of CP1 on gamma low-band oscillations. In conclusion, our results showed that KET presents excitatory and time-dependent effects on hippocampal EEG bands activity. KET excitatory effects on EEG were prevented by CP alone and in some situations potentiated by its combination with ALA. Copyright © 2016 Elsevier Ltd. All rights reserved.

The combination of FK506 and an anti-CD147 mAb exerts potential therapeutic effects on a mouse model of collagen-induced arthritis.

PubMed

Luan, Jing; Zhang, Kui; Yang, Peng; Zhang, Yang; Feng, Fei; Zhu, Yu-Meng; Zhu, Ping; Chen, Zhi-Nan

2018-05-25

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and excessive T lymphocyte activation plays a critical role in the development of inflammation. CD147 is an antigen related to T cell activation, CD147 blockade exerts beneficial effects on RA. FK506, also known as tacrolimus, exerts strong immunosuppressive effects by inhibiting T cell activation. In this study, RL73 (an anti-mouse CD147 functional-grade purified antibody) and FK506 were co-administered to mice with collagen-induced arthritis (CIA). As expected, the combination of these two drugs produced superior therapeutic effects than either drug alone and enabled the administration of each drug at a lower dose. Moreover, joint damage and destruction were significantly improved in mice injected with both FK506 and RL73 compared with mice injected with either agent alone. These effects might have been observed because the proportions of CD4 + T and CD8 + T cells in the mouse spleen of the combination regimen were clearly decreased compared with each monotherapy. In addition, the proportions of Th2 subsets in the mouse spleen and peripheral blood were clearly increased, and the serum levels of the cytokines interleukin 4 (IL-4) and IL-10 were markedly increased in mice treated with the combination therapy compared with the other groups of mice. The splenic total number of T lymphocytes also showed that the inhibition of T lymphocytes was the most obvious in the combined treatment group. Based on the results from the present study, combining FK506 and the anti-CD147 mAb might be a new practical therapeutic option for the treatment of RA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

PubMed

Haig, Jennifer; Barbeau, Martin; Ferreira, Alberto

2016-07-01

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet: A comparative study of combination therapy versus monotherapy.

PubMed

Mohamed, Maha Tarek; Abuelezz, Sally A; Atalla, Suzi Sobhy; El Aziz, Lobna Fouad Abd; Gorge, Sonia Salib

2017-05-01

Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD). 60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy. OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFα, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the mono-therapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy. Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of The Combined Effects of Hyperthermia, Cobalt-60 Gamma Rays and IUdR on Cultured Glioblastoma Spheroid Cells and Dosimetry Using TLD-100

PubMed Central

Neshasteh-Riz, Ali; Rahdani, Rozhin; Mostaar, Ahmad

2014-01-01

Objective In radiation treatment, the irradiation which is effective enough to control the tumors far exceeds normal-tissues tolerance. Thus to avoid such unfavourable outcomes, some methods sensitizing the tumor cells to radiation are used. Iododeoxyuridine (IUdR) is a halogenated thymidine analogue that known to be effective as a radiosensitizer in human cancer therapy. Improving the potential efficacy of radiation therapy after combining to hyperthermia depends on the magnitude of the differential sensitization of the hyperthermic effects or on the differential cytotoxicity of the radiation effects on the tumor cells. In this study, we evaluated the combined effects of IUdR, hyperthermia and gamma rays of 60Co on human glioblastoma spheroids culture. Materials and Methods In this experimental study,the cultured spheroids with 100µm diameter were treated by 1 µM IUdR, 43°C hyperthermia for an hour and 2 Gy gamma rays, respectively. The DNA damages induced in cells were compared using alkaline comet assay method, and dosimetry was then performed by TLD-100. Comet scores were calculated as mean ± standard error of mean (SEM) using one-way ANOVA. Results Comparison of DNA damages induced by IUdR and hyperthermia + gamma treatment showed 2.67- and 1.92-fold enhancement, respectively, as compared to the damages induced by radiation alone or radiation combined IUdR. Dosimetry results showed the accurate dose delivered to cells. Conclusion Analysis of the comet tail moments of spheroids showed that the radiation treatments combined with hyperthermia and IUdR caused significant radiosensitization when compared to related results of irradiation alone or of irradiation with IUdR. These results suggest a potential clinical advantage of combining radiation with hyperthermia and indicate effectiveness of hyperthermia treatment in inducing cytotoxicity of tumor cells. PMID:24611138

Combination of a GnRH agonist with an antagonist prevents flare-up effects and protects primordial ovarian follicles in the rat ovary from cisplatin-induced toxicity: a controlled experimental animal study

PubMed Central

2013-01-01

Background With the continuous improvement of surgery and chemotherapeutic treatments, many tumour patients increasingly achieve long-term survival and can even be completely cured. However, platinum-containing drugs, which are widely used to treat a variety of types of cancer, cause menstrual disorders and ovarian failure, which in turn lead to infertility. Thus far, gonadotropin releasing hormone (GnRH) agonist (GnRHa) and antagonist (GnRHant) are reported to act as protective agents of the ovary in chemotherapy through the inhibition of the female gonadal axis. Nevertheless, they both have disadvantages that limit their use. GnRHa causes a flare-up effect during the first week after administration, and no long-acting GnRHant agent is available. GnRHa combined with GnRHant may prevent the flare-up effect of GnRHa and rapidly inhibit the female gonadal axis. Several clinical studies with small sample sizes have reported controversial conclusions. In this strictly controlled animal study, we investigated the advantages of combination treatment with GnRHa and GnRHant. Methods Rats aged 12 weeks were divided into six groups: Control, cisplatin (CDDP), GnRHa, GnRHant, Combination (sht, short-term) and Combination (lng, long-term) of GnRHa and GnRHant. The last four groups received Triptorelin (1 mg/kg·d, for 14 days), Cetrorelix (0.5 mg/kg·d, for 10 days), a combination of Triptorelin (1 mg/kg·d, for 10 days) and Cetrorelix (0.5 mg/kg·d, for 10 days) in the long-term group and for 3 days in the short-term group. The Control and CDDP groups received saline (1 ml/kg·d, for 10 day). Then, all groups apart from the Control group received cisplatin (1 mg/kg·d, for 10 days), and the Control group received another 10 days of saline as described above. Blood samples were collected to detect the serum levels of E2, LH and FSH. Observation of oestrous cyclicity was also performed after drug administration. Finally, bilateral ovaries were collected for histological study and follicle counting. Results We observed a flare-up effect in rats treated with GnRHa, but not in any of the combination groups. The percentage of normal cyclicity increased from 0% in the CDDP group to 25.0%, 33.3%, 66.7% and 41.7%, in the GnRHa, GnRHant, combination (lng) and combination (sht) groups, respectively. Pretreatment with GnRHa, GnRHant and combination (lng) significantly protected the primordial follicles from destruction by preserving 57.6%, 63.4%, 87.1% and 60.4% of the follicles, respectively. Conclusions The combination of a GnRH agonist with antagonist completely prevented the flare-up effect and enhanced the protective effect of the ovary from cisplatin-induced gonadotoxicity in rats. PMID:23452939