WorldWideScience

Sample records for beta-quinine drug combination

  1. Drug Combinations for Visceral Leishmaniasis

    OpenAIRE

    Olliaro, P. L.

    2010-01-01

    PURPOSE OF REVIEW: Several attempts have been made to combine drugs for treating visceral leishmaniasis, but only recently have effective drugs become available and combinations been tested systematically. RECENT FINDINGS: Sequential treatments with liposomal amphotericin B followed by miltefosine or paromomycin (as short as 7 days), as well as the concomitant administration of miltefosine and paromomycin (for 10 days) are very effective in India (>95%). Sodium stibogluconate plus paromomycin...

  2. Antimalarial drug resistance and combination chemotherapy.

    OpenAIRE

    White, N.

    1999-01-01

    Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the cha...

  3. Synergistic drug combinations improve therapeutic selectivity

    OpenAIRE

    Lehàr, Joseph; Krueger, Andrew S.; Avery, William; Heilbut, Adrian M; Johansen, Lisa M.; Price, E. Roydon; Rickles, Richard J.; Short, Glenn F; Staunton, Jane E.; jin, xiaowei; Lee, Margaret S.; Zimmermann, Grant R; Borisy, Alexis A.

    2009-01-01

    Prevailing drug discovery approaches focus on compounds with molecular selectivity, inhibiting disease-relevant targets over others in vitro. However in vivo, many such agents are not therapeutically selective, either because of undesirable activity at effective doses or because the biological system responds to compensate. In theory, drug combinations should permit increased control of such complex biology, but there is a common concern that therapeutic synergy will generally be mirrored by ...

  4. PHARMACOECONOMIC ANALYSIS OF ANTIHYPERTENSIVE DRUG COMBINATIONS USE

    Directory of Open Access Journals (Sweden)

    E. I. Tarlovskaya

    2015-09-01

    Full Text Available Aim. To pursue pharmacoeconomic analysis of two drug combinations of ACE inhibitor (enalapril and diuretic.Material and methods. Patients with arterial hypertension degree 2 and diabetes mellitus type 2 without ischemic heart disease (n=56 were included into the study. Blood pressure (BP dynamics and cost/effectiveness ratio were evaluated.Results. In group A (fixed combination of original enalapril/hydrochlorothiazide 61% of patients achieved target BP level with initial dose, and the rest 39% of patients – with double dose. In group B (non-fixed combination of generic enalapril/indapamide 60% of patients achieved the target BP with initial dose of drugs, 33% - with double dose of ACE inhibitor, and 7% - with additional amlodipine administration. In patients of group A systolic BP (SBP reduction was 45.82±1.23 mm Hg by the 12th week vs. 40.0±0.81 mm Hg in patients of group B; diastolic BP (DBP reduction was 22.47±1.05 mm Hg and 18.76±0.70 mm Hg, respectively, by the 12th week of treatment. In the first month of treatment costs of target BP achievement was 298.62 rubles per patient in group A, and 299.50 rubles – in group B; by the 12th week of treatment – 629.45 and 631.22 rubles, respectively. Costs of SBP and DBP reduction by 1 mm Hg during 12 weeks of therapy were 13 and 27 rubles per patient, respectively, in group A, and 16 and 34 rubles per patient, respectively, in group B.Conclusion. The original fixed combination (enalapril+hydrochlorothiazide proved to be more clinically effective and more cost effective in the treatment of hypertensive patients in comparison with the non-fixed combination of generic drugs (enalapril+indapamide.

  5. Combined use of ECT and psychotropic drugs

    Directory of Open Access Journals (Sweden)

    Wojciech Merk

    2015-12-01

    Full Text Available Electroconvulsive therapy (ECT,despite a significant psychopharmacological development and introduction of modern drugs in recent years, is still an important, biological treatment of proven, high clinical efficacy. In the management algorithms it is still considered as a method of choice in treatment of drug-resistant patients. No wider use of ECTmay in part result from fears of potential interactions with pharmacotherapy, or need to interrupt the current treatment. The issue of potential impact of pharmacotherapy on many procedure parameters, including mostly seizure threshold and therefore indirectly clinical effect, is still up-to-date. Systematic studies have revised the existing theories about restrictions in the administration of medications during ECT treatment. Nowadays more often not only the safety of such procedure, but also possibility of synergistic therapeutic effect of ECT and psychopharmacology is highlighted. The authors present previous reports on combined use of pharmacotherapy and ECT, safety or potential risks associated with this treatment and proposals of scientific bodies in this regard. Interpretative limitations of conducted research, including especially case reports or observations of small groups, which requires further studies involving more numerous patient populations is noteworthy.

  6. Feedback System Control: optimizing drug combinations for tuberculosis treatment

    OpenAIRE

    Silva Vite, Aleidy Marlene

    2014-01-01

    Over the past years, numerous reports have surfaced demonstrating the outstanding superiority of combinatorial therapies over single drug treatments, one such example was the successful treatment of the human immunodeficiency virus with a combination therapy. The main problem faced when designing a multi-drug therapy is that combining a set of drugs at different possible concentrations yields a large testing parametric space, and thus the search of an optimal combination becomes a major chall...

  7. Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

    Science.gov (United States)

    Camacho, Kathryn Militar

    Chemotherapy combinations for cancer treatments harbor immense therapeutic potentials which have largely been untapped. Of all diseases, clinical studies of drug combinations are the most prevalent in oncology, yet their effectiveness is disputable, as complete tumor regressions are rare. Our research has been devoted towards developing delivery vehicles for combinations of chemotherapy drugs which elicit significant tumor reduction yet limit toxicity in healthy tissue. Current administration methods assume that chemotherapy combinations at maximum tolerable doses will provide the greatest therapeutic effect -- a presumption which often leads to unprecedented side effects. Contrary to traditional administration, we have found that drug ratios rather than total cumulative doses govern combination therapeutic efficacy. In this thesis, we have developed nanoparticles to incorporate synergistic ratios of chemotherapy combinations which significantly inhibit cancer cell growth at lower doses than would be required for their single drug counterparts. The advantages of multi-drug incorporation in nano-vehicles are many: improved accumulation in tumor tissue via the enhanced permeation and retention effect, limited uptake in healthy tissue, and controlled exposure of tumor tissue to optimal synergistic drug ratios. To exploit these advantages for polychemotherapy delivery, two prominent nanoparticles were investigated: liposomes and polymer-drug conjugates. Liposomes represent the oldest class of nanoparticles, with high drug loading capacities and excellent biocompatibility. Polymer-drug conjugates offer controlled drug incorporations through reaction stoichiometry, and potentially allow for delivery of precise ratios. Here, we show that both vehicles, when armed with synergistic ratios of chemotherapy drugs, significantly inhibit tumor growth in an aggressive mouse breast carcinoma model. Furthermore, versatile drug incorporation methods investigated here can be broadly

  8. [Grapefruit juice and drugs: a hazardous combination?].

    Science.gov (United States)

    Lohezic-Le Devehat, F; Marigny, K; Doucet, M; Javaudin, L

    2002-01-01

    A single glass of grapefruit juice can improve the oral bioavailability of a drug thus either increasing its efficacy or enhancing its adverse effects particularly if the therapeutic index is narrow. Grapefruit juice acts by inhibiting presystemic drug metabolism mediated by CYP P450 3A4 in the small bowel and this interaction would appear to be more relevant if the CYP 3A4 content is high and the drug has a strong first pass degradation. Intestinal P-glycoprotein may also be affected by grapefruit juice. The compounds responsible for this food-drug interaction have not as yet been identified but this phenomenon could result from a complex synergy between flavonoids (naringin, naringenin), furanocoumarins (6',7'-dihydroxybergamottin, bergamottin) and sesquiterpen (nootkatone). In our study, we report the mechanisms of action of grapefruit juice and the interactions between grapefruit juice and 42 drugs; to date, only 12 drugs showed no interaction. Taking these results into consideration, patients should be educated about grapefruit juice intake with medication. PMID:12611197

  9. A streamlined search technology for identification of synergistic drug combinations.

    Science.gov (United States)

    Weiss, Andrea; Berndsen, Robert H; Ding, Xianting; Ho, Chih-Ming; Dyson, Paul J; van den Bergh, Hubert; Griffioen, Arjan W; Nowak-Sliwinska, Patrycja

    2015-01-01

    A major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a design of experiment approach, for rapidly finding optimal drug mixtures with minimal experimental effort. We tested combinations in an in vitro assay for the viability of a renal cell adenocarcinoma (RCC) cell line, 786-O. An iterative cycle of in vitro testing and s-FSC analysis was repeated a few times until an optimal low dose combination was reached. Starting with ten drugs that target parallel pathways known to play a role in the development and progression of RCC, we identified the best overall drug combination, being a mixture of four drugs (axitinib, erlotinib, dasatinib and AZD4547) at low doses, inhibiting 90% of cell viability. The removal of AZD4547 from the optimized drug combination resulted in 80% of cell viability inhibition, while still maintaining the synergistic interaction. These optimized drug combinations were significantly more potent than monotherapies of all individual drugs (p < 0.001, CI < 0.3). PMID:26416286

  10. Drug-device combination products: regulatory landscape and market growth.

    Science.gov (United States)

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. PMID:26380388

  11. Quantitative phenotypic and pathway profiling guides rational drug combination strategies

    Directory of Open Access Journals (Sweden)

    NeilOCarragher

    2014-05-01

    Full Text Available Advances in target-based drug discovery strategies have enabled drug discovery groups in academia and industry to become very effective at generating molecules that are potent and selective against single targets. However, it has become apparent from disappointing results in recent clinical trials that a major challenge to the development of successful targeted therapies for treating complex multifactorial diseases is overcoming heterogeneity in target mechanism among patients and inherent or acquired drug resistance. Consequently, reductionist target directed drug-discovery approaches are not appropriately tailored towards identifying and optimizing multi-targeted therapeutics or rational drug combinations for complex disease. In this article, we describe the application of emerging high-content phenotypic profiling and analysis tools to support robust evaluation of drug combination performance following dose-ratio matrix screening. We further describe how the incorporation of high-throughput reverse phase protein microarrays with phenotypic screening can provide rational drug combination hypotheses but also confirm the mechanism-of-action of novel drug combinations, to facilitate future preclinical and clinical development strategies.

  12. Prediction of resistance development against drug combinations by collateral responses to component drugs

    DEFF Research Database (Denmark)

    Munck, Christian; Gumpert, Heidi; Nilsson Wallin, Annika;

    2014-01-01

    Resistance arises quickly during chemotherapeutic selection and is particularly problematic during long-term treatment regimens such as those for tuberculosis, HIV infections, or cancer. Although drug combination therapy reduces the evolution of drug resistance, drug pairs vary in their ability to...... adaptation to the component drugs. Then, using engineered E. coli strains, we confirmed that drug resistance mutations that imposed collateral sensitivity were suppressed in a drug pair growth environment. These results provide a framework for rationally selecting drug combinations that limit resistance...... do so. Thus, predictive models are needed to rationally design resistance-limiting therapeutic regimens. Using adaptive evolution, we studied the resistance response of the common pathogen Escherichia coli to 5 different single antibiotics and all 10 different antibiotic drug pairs. By analyzing the...

  13. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  14. The Drug Sensitivity of Cyclosporine A Combined with Antineoplastic Drugs in Retinoblastoma in Vitro

    Institute of Scientific and Technical Information of China (English)

    Wanli Liu; Zhongyao Wu

    2005-01-01

    Purpose: To study cyclosporine A inhibition on the fresh retinoblastoma cells in vitro and increasing the drug sensitivity after combined with different antineoplastic drugs.Methods: To study the growth curve of cyclosporine A on 27 samples of primary retinoblastoma cells by MTT assay and to study the change of the drug sensitivity by cyclosporine A combined with seven antineoplastic drugs.Results: The average IC50 of cyclosporine A on the 27 retinoblastoma cells is 67.81μg/ml and the average inhibitive rate of these samples is 26.1% when cyclosporine A is in the concentration of 2μg/ml. The inhibitive rates all got improved after the seven antineoplastic drugs combined with cyclosporine A and the increasing average inhibitive rate is more than 5.Conclusion: Cyclosporine A can inhibit retinoblastoma cells in vitro and its inhibitive effect is dose dependent. Moreover it can enhance the inhibition of multiple antineoplastic drugs on retinoblastoma cells.

  15. Combinations of drugs in the Treatment of Obesity

    Directory of Open Access Journals (Sweden)

    Marcio C. Mancini

    2010-07-01

    Full Text Available Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry.

  16. Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

    Directory of Open Access Journals (Sweden)

    Olliaro P

    2004-01-01

    Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

  17. Phentermine-topiramate: First combination drug for obesity

    OpenAIRE

    Singh, Jagjit; Kumar, Rajiv

    2015-01-01

    Obesity is spreading globally at an alarming speed. The management of obesity is multifaceted and includes lifestyle modifications as the cornerstone. Until only orlistat was approved for long term use in obesity. The US Food and Drug Administration granted approval to a fixed dose mid 2012 combination of phentermine immediate release and topiramate extended release in 2012 for treatment of obese patients or overweight patients with comorbid conditions. The new drug has shown significant weig...

  18. Fitness of Leishmania donovani parasites resistant to drug combinations.

    OpenAIRE

    Raquel García-Hernández; Verónica Gómez-Pérez; Santiago Castanys; Francisco Gamarro

    2015-01-01

    Drug resistance represents one of the main problems for the use of chemotherapy to treat leishmaniasis. Additionally, it could provide some advantages to Leishmania parasites, such as a higher capacity to survive in stress conditions. In this work, in mixed populations of Leishmania donovani parasites, we have analyzed whether experimentally resistant lines to one or two combined anti-leishmanial drugs better support the stress conditions than a susceptible line expressing luciferase (Luc lin...

  19. 21 CFR 300.50 - Fixed-combination prescription drugs for humans.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Fixed-combination prescription drugs for humans. 300.50 Section 300.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE GENERAL Combination Drugs § 300.50 Fixed-combination...

  20. Partnership to Explore New Drug Combination for Pancreatic Cancer | Poster

    Science.gov (United States)

    By Frank Blanchard, Staff Writer Scientists at NCI and Frederick National Laboratory for Cancer Research (FNLCR) are partnering with the Lustgarten Foundation to test whether a vitamin D derivative will make a difference when combined with a conventional anticancer drug in treating tumors of the pancreas.

  1. Radio Frequency-Activated Nanoliposomes for Controlled Combination Drug Delivery.

    Science.gov (United States)

    Malekar, Swapnil A; Sarode, Ashish L; Bach, Alvin C; Bose, Arijit; Bothun, Geoffrey; Worthen, David R

    2015-12-01

    This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance ((31)P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process. PMID:25899799

  2. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  3. ANTIBACTERIAL ACTIVITY OF COMBINATION DRUGS FOR TREATING VAGINOSIS DIFFERENT ETIOLOGIES

    Directory of Open Access Journals (Sweden)

    Bobritskaya L. A.,

    2014-01-01

    Full Text Available Investigated the antimicrobial activity of the combination preparation in capsules "Meraflam" clinical of microbial strains isolated from patients with bacterial vaginosis . Experimentally proved the therapeutic dose of 0.3 g ornidazole in combination with Flamini 0.05 g, improve tolerability and expand the range of antibacterial action of the drug. In view of the antimicrobial capacity of diclofenac sodium from the combination of ofloxacin proposed for use in an integrated circuit - inflammatory treatment of infectious diseases , including bacterial vaginosis.

  4. Combined drug medium with isoniazid and rifampicin for identification of multi-drug resistant Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Nalini S

    2010-01-01

    Full Text Available A low-cost method of detecting multi-drug resistant Mycobacterium tuberculosis (MDR-TB with the possibility of quick adoption in a resource limited setting is urgently required. We conducted a study combining isoniazid and rifampicin in a single LJ medium, to detect MDR-TB strains. Combined and individual drug media showed 100% concordance for the detection of MDR-TB and susceptible strains by proportion method. Considering the results, combined isoniazid and rifampicin containing medium could be considered for use in settings where the sole detection of MDR-TB strains is justified.

  5. Fitness of Leishmania donovani parasites resistant to drug combinations.

    Directory of Open Access Journals (Sweden)

    Raquel García-Hernández

    2015-04-01

    Full Text Available Drug resistance represents one of the main problems for the use of chemotherapy to treat leishmaniasis. Additionally, it could provide some advantages to Leishmania parasites, such as a higher capacity to survive in stress conditions. In this work, in mixed populations of Leishmania donovani parasites, we have analyzed whether experimentally resistant lines to one or two combined anti-leishmanial drugs better support the stress conditions than a susceptible line expressing luciferase (Luc line. In the absence of stress, none of the Leishmania lines showed growth advantage relative to the other when mixed at a 1:1 parasite ratio. However, when promastigotes from resistant lines and the Luc line were mixed and exposed to different stresses, we observed that the resistant lines are more tolerant of different stress conditions: nutrient starvation and heat shock-pH stress. Further to this, we observed that intracellular amastigotes from resistant lines present a higher capacity to survive inside the macrophages than those of the control line. These results suggest that resistant parasites acquire an overall fitness increase and that resistance to drug combinations presents significant differences in their fitness capacity versus single-drug resistant parasites, particularly in intracellular amastigotes. These results contribute to the assessment of the possible impact of drug resistance on leishmaniasis control programs.

  6. Synergism in Combined Use of Oral Antihyperglycemic Drugs

    Directory of Open Access Journals (Sweden)

    Sorokina Y.А.

    2014-09-01

    Full Text Available The aim of the investigation was to study the capabilities of combined use of metformin and vildagliptin, and its effect on glycemia and oxidative stress parameters in patients with newly diagnosed type 2 diabetes mellitus (DM 2. Materials and Methods. The study involved 37 patients with DM 2, they were divided (after two-week metformin dose titration into two groups by simple random sampling. Group 1 patients (n=18 were administered metformin at a dose of 1700 mg a day, group 2 patients (n=19 — the combination of metformin (1000 mg a day with vildagliptin (50 mg a day. Group 3 — a control group (n=20 consisted of subjects without carbohydrate metabolism imbalance. We studied glycemia indices (fasting blood plasma glucose, glycosylated hemoglobin, the level of molecular products of lipid peroxidation (diene and triene conjugates, malon dialdehyde, intensity of oxidative protein modification by the level of carbonyl derivatives, syperoxide dismutase and catalase activity before and 3 months after therapy. Results. Combined use of metformin (1000 mg a day and vildagliptin (50 mg a day in patients with newly diagnosed DM 2 showed the synergism of their antihyperglycemic and antioxidant effect. The mentioned combination of drugs compared to metformin monotherapy (1700 mg a day enables to reduce side effect rate and significantly increase catalase activity. Conclusion. The results of combined use of metformin and vildagliptin demonstrated the capability of DM 2 therapy based on rational choice of the combination of antihyperglycemic drugs relying on their synergistic properties.

  7. Drug combination against single drug treatment in radiation protection of the bone marrow CFU

    International Nuclear Information System (INIS)

    The effectiveness of two doses of WR-2721 (300 mg/kg and 150 mg/kg body weight) alone or in combination with an optimal dose (20 mg/kg body weight) of MPG, on the mouse bone marrow was studied by the exogenous spleen colony assay (CFU-s) after a single whole body exposure to 4.5 Gy of gamma radiation. Both the drugs individually increased the number of spleen colonies significantly above that of the irradiated control indicating higher stem cell survival. WR-2721 treatment gave better protection than MPG. MPG was more effective when administered within 5 min before or after irradiation than when given 30 to 25 min before irradiation. The combination of WR-2721, at either dose, with 20 mg/kg MPG gave an increase in the stem cell survival as compared to the single drug treatments and this effect was synergistic at 300 mg/kg WR-2721. MPG treatment within 5 min after irradiation produced a slightly higher CFU-s count than when the drug was injected before irradiation, though the difference was not statistically significant. It is concluded that in addition to the doses of the drug, the time of administration also could influence the effect of drug combinations. (orig.)

  8. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1

    Directory of Open Access Journals (Sweden)

    Sharma Akhilesh

    2009-12-01

    Full Text Available Abstract Background Combination antiretroviral (AR therapy continues to be the mainstay for HIV treatment. However, antiretroviral drug nonadherence can lead to the development of resistance and treatment failure. We have designed nanoparticles (NP that contain three AR drugs and characterized the size, shape, and surface charge. Additionally, we investigated the in vitro release of the AR drugs from the NP using peripheral blood mononuclear cells (PBMCs. Methods Poly-(lactic-co-glycolic acid (PLGA nanoparticles (NPs containing ritonavir (RTV, lopinavir (LPV, and efavirenz (EFV were fabricated using multiple emulsion-solvent evaporation procedure. The nanoparticles were characterized by electron microscopy and zeta potential for size, shape, and charge. The intracellular concentration of AR drugs was determined over 28 days from NPs incubated with PBMCs. Macrophages were imaged by fluorescent microscopy and flow cytometry after incubation with fluorescent NPs. Finally, macrophage cytotoxicity was determined by MTT assay. Results Nanoparticle size averaged 262 ± 83.9 nm and zeta potential -11.4 ± 2.4. AR loading averaged 4% (w/v. Antiretroviral drug levels were determined in PBMCs after 100 μg of NP in 75 μL PBS was added to media. Intracellular peak AR levels from NPs (day 4 were RTV 2.5 ± 1.1; LPV 4.1 ± 2.0; and EFV 10.6 ± 2.7 μg and continued until day 28 (all AR ≥ 0.9 μg. Free drugs (25 μg of each drug in 25 μL ethanol added to PBMCs served as control were eliminated by 2 days. Fluorescence microscopy and flow cytometry demonstrated phagocytosis of NP into monocytes-derived macrophages (MDMs. Cellular MTT assay performed on MDMs demonstrated that NPs are not significantly cytotoxic. Conclusion These results demonstrated AR NPs could be fabricated containing three antiretroviral drugs (RTV, LPV, EFV. Sustained release of AR from PLGA NP show high drug levels in PBMCs until day 28 without cytotoxicity.

  9. Experimental basis for the combination of irradiation with cytotoxic drugs

    International Nuclear Information System (INIS)

    For the treatment of therapy resistant tumours the combination of irradiation with chemical substances, especially cytotoxic drugs, can have advantages. In order to obtain supraadditive effects it is reasonable to know the mechanism of interaction. In this respect interactions are very important on the level of intracellular recovery processes, of repopulation, and of hypoxic cells. Substances have been discussed which interact with ionizing radiation on these levels. Especially the modification of recovery processes can increase the radiation effects efficiently. In this connection substances like actinomycin D, bleomycin, adriamycin, and newer drugs like aclacinomycin are of interest. For such a treatment tumours with a high capacity of recovery must be considered. An individual selection would have great advantages therefore. (orig.)

  10. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning.

    Science.gov (United States)

    Chen, Xing; Ren, Biao; Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

    2016-07-01

    Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

  11. ANTIHYPERTENSIVE TREATMENT WITH COMBINED DRUG OF LOSARTAN AND HYDROCHLOROTHIAZIDE

    OpenAIRE

    R. M. Linchak; K. M. Shumilova; A. D. Martinyuk; T. A. Gusaim; E. V. Semyonova; L. G. Zhirova; S. A. Boitsov

    2016-01-01

    Aim:  to evaluate efficiency and safety of the combined antihypertensive drug Lozap Plus (50 mg losartan, 12,5 mg hydrochlorothiazide) in patients with arterial hypertension (AH) of I-III grade with high and very high cardiovascular risk. Material and methods: 30 patients with AH of I-III grade (13 men and 17 women aged 51.9±1.9) were observed. Patients received Lozan Plus (Zentiva, Czech Republic) 1 time in the morning during 12 weeks. Ambulatory blood pressure monitoring (ABPM), echocardiog...

  12. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    Science.gov (United States)

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

  13. Drug combination adds fuel to US abortion debate.

    Science.gov (United States)

    Rutter, T L

    1995-09-16

    A recent study in the US showed that abortion was achieved in 171/178 women aged 18 to 47 with pregnancies of 63 days or less duration through the administration of an intramuscular injection of methotrexate (a drug used to treat cancer) followed five to seven days later with a dose of misoprostol (used to treat ulcers). The report of this study prompted the founder of the anti-abortion group Operation Rescue to threaten the report's author with being "hunted down and tried for genocide" should abortion ever be made illegal. While the National Abortion Rights Action League urged that the procedure be judged on medical not political terms, a spokesperson for the National Right to Life Committee expressed concern for the reproductive and psychological health of women undergoing medical abortions. The Population Council is currently completing clinical trials of the regimen which employs RU-486 to achieve medical abortion and expects to file a new drug application with the US Food and Drug Administration (FDA) in 1996. The methotrexate/misoprostol combination would be much less expensive than RU-486 (approximately $10 compared to $250 at current prices), and a pharmaceutical company is currently attempting to raise the six million dollars necessary to fund the large-scale clinical trials which must precede FDA approval. While the availability of medical abortions would make the procedure much more accessible and private for women, proper counseling must be given to the women to avoid unwanted side effects and so that the women know what to expect. PMID:7549678

  14. Potential Drug Combinations to Reduce Cardiovascular Disease Burden in Diabetes.

    Science.gov (United States)

    Pillarisetti, Sivaram

    2016-03-01

    The major cause of death and complications in patients with type 2 diabetes (T2DM) is cardiovascular disease (CVD). More than 60% of all patients with T2DM die of CVD, and an even greater percentage have serious complications. The impact of glucose lowering on cardiovascular complications is a hotly debated issue and recent large clinical trials reported no significant decrease in cardiovascular events with intensive glucose control. Risk remains high even after correcting diabetes-associated dyslipidemia with drugs such as fibrates and niacin. Data from several clinical studies show that postprandial glucose and lipids have a strong predictive value on myocardial infarction (MI) and mortality. However, strategies to reduce postprandial hyperglycemia and/or lipemia through increased utilization of glucose and/or triglycerides (TG) have been shown to not be effective in reducing the CVD burden. In this review, I discus the preferred ways to reduce postprandial glucose and TG with combinations of currently marketed drugs with potential benefit in CVD. PMID:26719218

  15. The economics of polypharmacology: fixed dose combinations and drug cocktails.

    Science.gov (United States)

    Wertheimer, A I

    2013-01-01

    The history of Fixed Dose Combination (FDC) oral drug products has been tumultuous over its history. Some FDCs were prepared for marketing purposes and others for clinical improvements. Often, the products prepared for marketing advantage ended up causing negative outcomes. However, in recent years, there has been a resurgence of FDCs as clinicians have found them adventitious for treatment of AIDS/HIV and for oral contraceptives, just to name two examples. International regulatory Agencies and most major drug regulatory agencies have established guidelines along with regulations concerning preparation, labeling and marketing for FDCs. The advantages of FDCs are said to be in the clinical realm where simplified therapy regimens are thought to enhance patient's medication taking compliance. On the financial side, health insurers and other payers normally save money from a decreased number of dispensing fees, the use of fewer bottles, labels, etc., and from the possible situation where the price of the FDC is less than the medication price of the two separate ingredients dispensed individually. Overall, there is a great deal of evidence in favor of appropriate FDCs. PMID:23410163

  16. High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations.

    Science.gov (United States)

    Mott, Bryan T; Eastman, Richard T; Guha, Rajarshi; Sherlach, Katy S; Siriwardana, Amila; Shinn, Paul; McKnight, Crystal; Michael, Sam; Lacerda-Queiroz, Norinne; Patel, Paresma R; Khine, Pwint; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Fontaine, Shaun D; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A; Ferrer, Marc; Renslo, Adam R; Inglese, James; Yuan, Jing; Roepe, Paul D; Su, Xin-Zhuan; Thomas, Craig J

    2015-01-01

    Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy. PMID:26403635

  17. Drug permeation and cellular interaction of amino acid-coated drug combination powders for pulmonary delivery.

    Science.gov (United States)

    Vartiainen, Ville; Bimbo, Luis M; Hirvonen, Jouni; Kauppinen, Esko I; Raula, Janne

    2016-05-17

    The effect of three amino acid coatings (l-leucine, l-valine and l-phenylalanine) on particle integrity, aerosolization properties, cellular interaction, cytocompatibility, and drug permeation properties of drug combination powder particles (beclomethasone dipropionate and salbutamol sulphate) for dry powder inhalation (DPI) was investigated. Particles with crystalline l-leucine coating resulted in intact separated particles, with crystalline l-valine coating in slightly sintered particles and with amorphous l-phenylalanine coating in strongly fused particles. The permeation of beclomethasone dipropionate across a Calu-3 differentiated cell monolayer was increased when compared with its physical mixture. Drug crystal formation was also observed on the Calu-3 cell monolayer. The l-leucine coated particles were further investigated for cytocompatibility in three human pulmonary (Calu-3, A549 and BEAS-2B) and one human macrophage (THP-1) cell lines, where they showed excellent tolerability. The l-leucine coated particles were also examined for their ability to elicit reactive oxygen species in pulmonary BEAS-2B and macrophage THP-1 cell lines. The study showed the influence of the amino acid coatings for particle formation and performance and their feasibility for combination therapy for pulmonary delivery. PMID:27034001

  18. Grapefruit Juice and Some Oral Drugs: A Bitter Combination

    OpenAIRE

    Vu, Minh Chau

    1999-01-01

    Grapefruit juice has been found to interact with many oral drugs when taken concomitantly. Studies have shown that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4)- an important enzyme involved in drug metabolism- via mechanism-based inactivation. Drug elimination is therefore prevented, and as a result, the bioavailability of many orally administered drugs is substantially increased when the patient ingests grapefruit juice. The grapefruit-drug interaction may result in severe side eff...

  19. Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

    Science.gov (United States)

    Park, Yoon-Dong; Sun, Wei; Salas, Antonio; Antia, Avan; Carvajal, Cindy; Wang, Amy; Xu, Xin; Meng, Zhaojin; Zhou, Ming; Tawa, Gregory J.; Dehdashti, Jean; Zheng, Wei; Henderson, Christina M.; Zelazny, Adrian M.

    2016-01-01

    ABSTRACT Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS) screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development. PMID:27486194

  20. WHEN YOUTH COMBINE DRUGS AND VIOLENCE: AN EXPLOSIVE COCKTAIL*

    OpenAIRE

    Brochu, Serge

    2013-01-01

    Young offenders held in youth rehabilitation centres constitute an at risk population for substance abuse and violence. This study will describe the relations between psychoactive substances (alcohol and illicit drugs) and violence among this population. More specifically, we will look at the roles played by: a) intoxication periods; b) the need for money to buy drugs; and c) the illicit drug distribution system in the manifestation of violent behaviour among young Canadian offenders. The dat...

  1. Exploiting Drug Repositioning for Discovery of a Novel HIV Combination Therapy ▿

    OpenAIRE

    Clouser, Christine L.; Patterson, Steven E.; Louis M Mansky

    2010-01-01

    The development of HIV drugs is an expensive and a lengthy process. In this study, we used drug repositioning, a process whereby a drug approved to treat one condition is used to treat a different condition, to identify clinically approved drugs that have anti-HIV activity. The data presented here show that a combination of two clinically approved drugs, decitabine and gemcitabine, reduced HIV infectivity by 73% at concentrations that had minimal antiviral activity when used individually. Dec...

  2. A Hadoop-Based Method to Predict Potential Effective Drug Combination

    OpenAIRE

    Yifan Sun; Yi Xiong; Qian Xu; Dongqing Wei

    2014-01-01

    Combination drugs that impact multiple targets simultaneously are promising candidates for combating complex diseases due to their improved efficacy and reduced side effects. However, exhaustive screening of all possible drug combinations is extremely time-consuming and impractical. Here, we present a novel Hadoop-based approach to predict drug combinations by taking advantage of the MapReduce programming model, which leads to an improvement of scalability of the prediction algorithm. By inte...

  3. Combined antiretroviral and anti-tuberculosis drug resistance following incarceration

    OpenAIRE

    Stott, K E; de Oliviera, T; Lessells, R.J.

    2013-01-01

    We describe a case of HIV/tuberculosis (TB) co-infection from KwaZulu-Natal, South Africa, characterised by drug resistance in both pathogens. The development of drug resistance was linked temporally to two periods of incarceration. This highlights the urgent need for improved integration of HIV/TB control strategies within prison health systems and within the broader public health framework.

  4. Systematic prediction of drug combinations based on clinical side-effects.

    Science.gov (United States)

    Huang, Hui; Zhang, Ping; Qu, Xiaoyan A; Sanseau, Philippe; Yang, Lun

    2014-01-01

    Drug co-prescription (or drug combination) is a therapeutic strategy widely used as it may improve efficacy and reduce side-effect (SE). Since it is impractical to screen all possible drug combinations for every indication, computational methods have been developed to predict new combinations. In this study, we describe a novel approach that utilizes clinical SEs from post-marketing surveillance and the drug label to predict 1,508 novel drug-drug combinations. It outperforms other prediction methods, achieving an AUC of 0.92 compared to an AUC of 0.69 in a previous method, on a much larger drug combination set (245 drug combinations in our dataset compared to 75 in previous work.). We further found from the feature selection that three FDA black-box warned serious SEs, namely pneumonia, haemorrhage rectum, and retinal bleeding, contributed mostly to the predictions and a model only using these three SEs can achieve an average area under curve (AUC) at 0.80 and accuracy at 0.91, potentially with its simplicity being recognized as a practical rule-of-three in drug co-prescription or making fixed-dose drug combination. We also demonstrate this performance is less likely to be influenced by confounding factors such as biased disease indications or chemical structures. PMID:25418113

  5. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1 chemical interaction between drugs, (2 protein interactions between drugs’ targets, and (3 target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.

  6. Combined antiretroviral and antituberculosis drug resistance following incarceration

    Directory of Open Access Journals (Sweden)

    Katharine Elizabeth Stott

    2013-09-01

    Full Text Available We describe a case of HIV/tuberculosis (TB co-infection from KwaZulu-Natal, South Africa, characterised by drug resistance in both pathogens. The development of drug resistance was linked temporally to two periods of incarceration. This highlights the urgent need for improved integration of HIV/TB control strategies within prison health systems and within the broader public health framework.

  7. Trigeminal neuralgia: successful antiepileptic drug combination therapy in three refractory cases

    OpenAIRE

    2011-01-01

    Antiepileptic drug combination therapy remains an empirical second-line treatment approach in trigeminal neuralgia, after treatment with one antiepileptic drug or other nonantiepileptic drugs have failed. The results in three patients followed in our clinic are not sufficient to draw definitive conclusions, but suggest the possibility of developing this type of therapeutic approach further.

  8. Involvement of drug transporters in the synergistic action of FOLFOX combination chemotherapy

    OpenAIRE

    Theile, Dirk; Grebhardt, Sina; Haefeli, Walter Emil; Weiss, Johanna

    2009-01-01

    Abstract FOLFOX is a cytostatic drug combination for adjuvant treatment of colorectal cancer (CRC) consisting of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin. The mechanism of synergistic interaction of these drugs is poorly understood and little is known concerning the role of drug transporters and the impact of oxaliplatin metabolites oxalate and dichloro-diaminocyclohexane platinum. We therefore investigated the influence of FOLFOX-components on drug transporter expression...

  9. The application of prodrug-based nano-drug delivery strategy in cancer combination therapy.

    Science.gov (United States)

    Ge, Yanxiu; Ma, Yakun; Li, Lingbing

    2016-10-01

    Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. PMID:27400243

  10. Mono- and combination drug therapies in hospitalized patients with bipolar depression. Data from the European drug surveillance program AMSP

    Directory of Open Access Journals (Sweden)

    Haeberle Anne

    2012-09-01

    Full Text Available Abstract Background For the pharmacological treatment of bipolar depression several guidelines exist. It is largely unknown, to what extent the prescriptions in daily clinical routine correspond to these evidence based recommendations and which combinations of psychotropic drugs are frequently used. Methods The prescriptions of psychotropic drugs were investigated of all in-patients with bipolar depression (n = 2246; time period 1994–2009 from hospitals participating in the drug surveillance program AMSP. For the drug use in 2010, 221 cases were analysed additionally. Results From 1994 to 2009, 85% of all patients received more than one class of psychotropic substances: 74% received antidepressants in combination therapy, 55% antipsychotics, 48% anticonvulsants and 33% lithium. When given in combination, lithium is the most often prescribed substance for bipolar depression (33%, followed by valproic acid (23%, mirtazapine and venlafaxine (16% each, quetiapine (15%, lamotrigine (14% and olanzapine (13%. Both, lithium and valproic acid are often combined with selective serotonin reuptake inhibitors (SSRI, but also with mirtazapine und venlafaxine. Combinations of more than one antidepressant occur quite often, whereby combinations with bupropion, paroxetine, fluoxetine or fluvoxamine are very rare. In 2010, quetiapine (alone and combined was the most frequently prescribed drug (39%; aripiprazole was administered in 10%. Conclusion Combinations of antidepressants (SSRI, mirtazapine, venlafaxine with mood stabilizers (lithium, valproic acid, lamotrigine and / or atypical antipsychotics (quetiapine, olanzapine are common. Of most of those combinations the efficacy has not been studied. The use of aripiprazole and the concomitant use of two or three antidepressants contrast the guidelines.

  11. Effect of combinations of marketed human anthelmintic drugs against Trichuris muris in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Keiser Jennifer

    2012-12-01

    Full Text Available Abstract Background Soil-transmitted helminth (STH infections are responsible for a huge public health burden, however treatment options are limited. The discovery and development of novel efficacious drugs or drug combinations for the treatment of STH infections therefore has a high research priority. Methods We studied drug combination effects using the main standard anthelmintics, albendazole, mebendazole, levamisole, pyrantel pamoate and ivermectin in the Trichuris muris model. Drug combinations were first tested in vitro and additive and synergistic combinations investigated further in vivo in female mice using ratios based on the ED50 of the respective drugs. Results In vitro all 10 combinations of the standard anthelmintics tested against T. muris revealed synergistic behavior. We identified three drug combinations in vivo as strongly synergistic, namely mebendazole-ivermectin (Combination index (CI=0.16, mebendazole-levamisole (CI=0.17 and albendazole-mebendazole (CI=0.23. For albendazole-ivermectin, moderate synergism was observed (CI=0.81 and for albendazole-levamisole a nearly additive effect was documented (CI=0.93 in vivo. Five combinations (albendazole-pyrantel pamoate, mebendazole-pyrantel pamoate, levamisole-pyrantel pamoate, levamisole-ivermectin and pyrantel pamoate-ivermectin were antagonistic in vivo. Conclusion Our results strengthen the evidence that combination chemotherapy might play a role in the treatment of Trichuris infections. Albendazole-mebendazole should be studied in greater detail in preclinical studies.

  12. Identification of drug combinations containing imatinib for treatment of BCR-ABL+ leukemias.

    Directory of Open Access Journals (Sweden)

    Yunyi Kang

    Full Text Available The BCR-ABL translocation is found in chronic myeloid leukemia (CML and in Ph+ acute lymphoblastic leukemia (ALL patients. Although imatinib and its analogues have been used as front-line therapy to target this mutation and control the disease for over a decade, resistance to the therapy is still observed and most patients are not cured but need to continue the therapy indefinitely. It is therefore of great importance to find new therapies, possibly as drug combinations, which can overcome drug resistance. In this study, we identified eleven candidate anti-leukemic drugs that might be combined with imatinib, using three approaches: a kinase inhibitor library screen, a gene expression correlation analysis, and literature analysis. We then used an experimental search algorithm to efficiently explore the large space of possible drug and dose combinations and identified drug combinations that selectively kill a BCR-ABL+ leukemic cell line (K562 over a normal fibroblast cell line (IMR-90. Only six iterations of the algorithm were needed to identify very selective drug combinations. The efficacy of the top forty-nine combinations was further confirmed using Ph+ and Ph- ALL patient cells, including imatinib-resistant cells. Collectively, the drug combinations and methods we describe might be a first step towards more effective interventions for leukemia patients, especially those with the BCR-ABL translocation.

  13. Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis.

    Science.gov (United States)

    Rey-Jurado, Emma; Tudó, Griselda; Martínez, José Antonio; González-Martín, Julian

    2012-05-01

    Fluoroquinolones such as ofloxacin are promising drugs to treat drug-resistant tuberculosis (TB) and have been proposed for shortening the treatment of TB. The objectives were to study the synergistic effect of the combinations of three drugs and to evaluate the in vitro interactions of the following combinations against Mycobacterium tuberculosis: A) isoniazid, rifampicin, and ethambutol and B) ofloxacin, rifampicin, and ethambutol using an adaptation of the two-dimensional chequerboard assay. A total of 12 isolates resistant to isoniazid or to isoniazid-streptomycin and 11 drug-susceptible isolates were tested. The fractional inhibitory concentration (FICI) was calculated as follows: FICI = FIC(A) + FICB + FIC(C) = A/MIC(A) + B/MIC(B) + C/MIC(C) where A, B and C were the MICs of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) were the individual MICs. The FICI was interpreted as synergism when the value was ≤0.75. In combination A, 11 drug-susceptible isolates decreased the individual MIC one to three dilutions, showing indifferent activity in 81.8% (FICI = 0.88-1.6) and synergistic activity in 18.1% (FICI = 0.6). In combination B, 21 out of the 23 isolates studied (91.3%) showed synergism (FICI = 0.31-0.62). In conclusion, adaptation of the two-dimensional chequerboard assay is a reliable method to study in vitro three-drug combinations. Both three-drug combinations tested may be useful against drug-resistant isolates, although the combination including ofloxacin showed better efficacy, being of potential use in drug-susceptible and isoniazid-resistant isolates. PMID:22342247

  14. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library

    Science.gov (United States)

    Feng, Jie; Shi, Wanliang; Zhang, Shuo; Sullivan, David; Auwaerter, Paul G.; Zhang, Ying

    2016-01-01

    Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10–20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under experimental stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that appear resistant in vitro to customary first-line antibiotics for Lyme disease. To identify more effective drugs with activity against the round body form of B. burgdorferi, we established a round body persister model induced by exposure to amoxicillin (50 μg/ml) and then screened the Food and Drug Administration drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven individual drugs scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. In this amoxicillin-induced round body model, some drug candidates such as daptomycin and clofazimine also displayed enhanced activity which was similar to a previous screen against stationary phase B. burgdorferi persisters not exposure to amoxicillin. Additional candidate drugs active against round bodies identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against amoxicillin-induced round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi

  15. Stimuli-free programmable drug release for combination chemo-therapy

    Science.gov (United States)

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-06-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  16. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs

    OpenAIRE

    SAHADEO PATIL; PANKAJ MAKNIKAR; SUSHILKUMAR WANKHADE; CHANDRAKIRAN UKESH; MAHENDRA RA

    2015-01-01

    Abstract. Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obta...

  17. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-induced Round Bodies of Borrelia burgdorferi Persisters from an FDA Drug Library

    Directory of Open Access Journals (Sweden)

    Jie eFeng

    2016-05-01

    Full Text Available Although currently recommended antibiotics for Lyme disease such as doxycycline or amoxicillin cure the majority of the patients, about 10-20% of patients treated for Lyme disease may experience lingering symptoms including fatigue, pain, or joint and muscle aches. Under stress conditions such as starvation or antibiotic exposure, Borrelia burgdorferi can develop round body forms, which are a type of persister bacteria that are not killed by current Lyme antibiotics. To identify more effective drugs that are active against the round bodies of B. burgdorferi, we established a round body persister model induced by amoxicillin and screened the Food and Drug Administration (FDA drug library consisting of 1581 drug compounds and also 22 drug combinations using the SYBR Green I/propidium iodide (PI viability assay. We identified 23 drug candidates that have higher activity against the round bodies of B. burgdorferi than either amoxicillin or doxycycline. Eleven of these scored better than metronidazole and tinidazole which have been previously described to be active against round bodies. While some drug candidates such as daptomycin and clofazimine overlapped with a previous screen against stationary phase B. burgdorferi persisters, additional drug candidates active against round bodies we identified include artemisinin, ciprofloxacin, nifuroxime, fosfomycin, chlortetracycline, sulfacetamide, sulfamethoxypyridazine and sulfathiozole. Two triple drug combinations had the highest activity against round bodies and stationary phase B. burgdorferi persisters: artemisinin/cefoperazone/doxycycline and sulfachlorpyridazine/daptomycin/doxycycline. These findings confirm and extend previous findings that certain drug combinations have superior activity against B. burgdorferi persisters in vitro, even if pre-treated with amoxicillin. These findings may have implications for improved treatment of Lyme disease.

  18. A hadoop-based method to predict potential effective drug combination.

    Science.gov (United States)

    Sun, Yifan; Xiong, Yi; Xu, Qian; Wei, Dongqing

    2014-01-01

    Combination drugs that impact multiple targets simultaneously are promising candidates for combating complex diseases due to their improved efficacy and reduced side effects. However, exhaustive screening of all possible drug combinations is extremely time-consuming and impractical. Here, we present a novel Hadoop-based approach to predict drug combinations by taking advantage of the MapReduce programming model, which leads to an improvement of scalability of the prediction algorithm. By integrating the gene expression data of multiple drugs, we constructed data preprocessing and the support vector machines and naïve Bayesian classifiers on Hadoop for prediction of drug combinations. The experimental results suggest that our Hadoop-based model achieves much higher efficiency in the big data processing steps with satisfactory performance. We believed that our proposed approach can help accelerate the prediction of potential effective drugs with the increasing of the combination number at an exponential rate in future. The source code and datasets are available upon request. PMID:25147789

  19. A Hadoop-Based Method to Predict Potential Effective Drug Combination

    Directory of Open Access Journals (Sweden)

    Yifan Sun

    2014-01-01

    Full Text Available Combination drugs that impact multiple targets simultaneously are promising candidates for combating complex diseases due to their improved efficacy and reduced side effects. However, exhaustive screening of all possible drug combinations is extremely time-consuming and impractical. Here, we present a novel Hadoop-based approach to predict drug combinations by taking advantage of the MapReduce programming model, which leads to an improvement of scalability of the prediction algorithm. By integrating the gene expression data of multiple drugs, we constructed data preprocessing and the support vector machines and naïve Bayesian classifiers on Hadoop for prediction of drug combinations. The experimental results suggest that our Hadoop-based model achieves much higher efficiency in the big data processing steps with satisfactory performance. We believed that our proposed approach can help accelerate the prediction of potential effective drugs with the increasing of the combination number at an exponential rate in future. The source code and datasets are available upon request.

  20. Anti-HIV Drug-Combination Nanoparticles Enhance Plasma Drug Exposure Duration as Well as Triple-Drug Combination Levels in Cells Within Lymph Nodes and Blood in Primates

    OpenAIRE

    Freeling, Jennifer P.; Koehn, Josefin; Shu, Cuiling; Sun, Jianguo; Ho, Rodney J. Y.

    2015-01-01

    HIV patients on combination oral drug therapy experience insufficient drug levels in lymph nodes, which is linked to viral persistence. Following success in enhancing lymph node drug levels and extending plasma residence time of indinavir formulated in lipid nanoparticles, we developed multidrug anti-HIV lipid nanoparticles (anti-HIV LNPs) containing lopinavir (LPV), ritonavir (RTV), and tenofovir (PMPA). These anti-HIV LNPs were prepared, characterized, scaled up, and evaluated in primates w...

  1. Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

    Directory of Open Access Journals (Sweden)

    Lisa Corina Barros de Andrade e Sousa1

    2016-01-01

    Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  2. Activity of Picolinic Acid in Combination with the Antiprotozoal Drug Quinacrine against Mycobacterium avium Complex

    OpenAIRE

    Shimizu, Toshiaki; Tomioka, Haruaki

    2006-01-01

    We studied the in vitro and in vivo antimicrobial activities of picolinic acid (PA) in combination with the antiprotozoal drug quinacrine against intramacrophage Mycobacterium avium complex (MAC). Quinacrine significantly potentiated the anti-MAC activity of PA, suggesting the usefulness of this combination in the clinical control of MAC infection.

  3. Activity of trovafloxacin in combination with other drugs for treatment of acute murine toxoplasmosis.

    OpenAIRE

    Khan, A. A.; Slifer, T; Araujo, F G; Polzer, R J; Remington, J S

    1997-01-01

    Current therapy for toxoplasmosis with a synergistic combination of pyrimethamine plus sulfadiazine or pyrimethamine plus clindamycin is not always efficacious and is frequently discontinued due to intolerable toxic effects in immunocompromised individuals, particularly those with AIDS. Trovafloxacin, a new fluoroquinolone with potent activity against Toxoplasma gondii, was examined for potential synergistic activity when combined with other drugs used for treatment of human toxoplasmosis. Co...

  4. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs

    Directory of Open Access Journals (Sweden)

    SAHADEO PATIL

    2015-05-01

    Full Text Available Abstract. Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obtained from cumin seeds using hydrodistillation technique and was later evaluated for the presence of major chemical constituents present in it using gas chromatography and mass spectrometry (GC-MS assay. The GC-MS assay revealed the abundance of γ-terpinene (35.42% followed by p-cymene (30.72%. The agar disc diffusion assay demonstrated highly potent antifungal effect against Candida species. Moreover, the combination of cumin essential oil (CEO with conventional antifungal drugs was found to reduce the individual MIC of antifungal drug suggesting the occurrence of synergistic interactions. Therefore, the therapy involving combinations of CEO and conventional antifungal drugs can be used for reducing the toxicity induced by antifungal drugs and at the same time enhancing their antifungal efficacy in controlling the infections caused due to Candida species.

  5. Sterilizing Activities of Novel Combinations Lacking First- and Second-Line Drugs in a Murine Model of Tuberculosis

    OpenAIRE

    Williams, Kathy; Minkowski, Austin; Amoabeng, Opokua; Peloquin, Charles A.; Taylor, Dinesh; Andries, Koen; Wallis, Robert S.; Mdluli, Khisimuzi E.; Eric L Nuermberger

    2012-01-01

    Novel oral regimens composed of new drugs with potent activity against Mycobacterium tuberculosis and no cross-resistance with existing agents are needed to shorten and simplify treatment for both drug-susceptible and drug-resistant tuberculosis. As part of a continuing effort to evaluate novel drug combinations for treatment-shortening potential in a murine model, we performed two long-term, relapse-based experiments. In the first experiment, several 3- and 4-drug combinations containing new...

  6. Effect and Prognostic Analysis of Treatment for Acute Myeloid Leukemia Using Chinese Drugs Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    胡晓梅; 刘锋; 郑春梅; 李柳; 刘池; 张姗姗; 肖海燕; 杨晓红; 王洪志; 许勇钢; 胡乃平; 麻柔

    2009-01-01

    Objective:To observe the clinical efficacy of Chinese drugs combined with chemotherapy in the treatment of acute myeloid leukemia(AML) and to investigate the prognostic relevance of the main parameters in AML treated with integrative medicine.Methods:Forty AML patients hospitalized at the authors' hospital were treated with Chinese drugs and chemotherapy.The routine examination,immunophenotype and karyotype analyses were carried out.The clinical efficacy was observed and the prognostic factors were analy...

  7. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action

    OpenAIRE

    Iermolenko T.I.

    2015-01-01

    Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total pl...

  8. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action.

    OpenAIRE

    Iermolenko, T. I.

    2015-01-01

    Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total pl...

  9. Numerical Model to Characterize the Size Increase of Combination Drug and Hygroscopic Excipient Nanoparticle Aerosols

    OpenAIRE

    Longest, P. Worth; Hindle, Michael

    2011-01-01

    Enhanced excipient growth is a newly proposed respiratory delivery strategy in which submicrometer or nanometer particles composed of a drug and hygroscopic excipient are delivered to the airways in order to minimize extrathoracic depositional losses and maximize lung retention. The objective of this study was to develop a validated mathematical model of aerosol size increase for hygroscopic excipients and combination excipient-drug particles and to apply this model to characterize growth und...

  10. Cell-based drug combination screening with a microfluidic droplet array system.

    Science.gov (United States)

    Du, Guan-Sheng; Pan, Jian-Zhang; Zhao, Shi-Ping; Zhu, Ying; den Toonder, Jaap M J; Fang, Qun

    2013-07-16

    We performed cell-based drug combination screening using an integrated droplet-based microfluidic system based on the sequential operation droplet array (SODA) technique. In the system, a tapered capillary connected with a syringe pump was used for multistep droplet manipulations. An oil-covered two-dimensional droplet array chip fixed in an x-y-z translation stage was used as the platform for cell culture and analysis. Complex multistep operations for drug combination screening involving long-term cell culture, medium changing, schedule-dependent drug dosage and stimulation, and cell viability testing were achieved in parallel in the semiopen droplet array, using multiple droplet manipulations including liquid metering, aspirating, depositing, mixing, and transferring. Long-term cell culture as long as 11 days was performed in oil-covered 500 nL droplets by changing the culture medium in each droplet every 24 h. The present system was applied in parallel schedule-dependent drug combination screening for A549 nonsmall lung cancer cells with the cell cycle-dependent drug flavopiridol and two anticancer drugs of paclitaxel and 5-fluorouracil. The highest inhibition efficiency was obtained with a schedule combination of 200 nM flavopiridol followed by 100 μM 5-fluorouracil. The drug consumption for each screening test was substantially decreased to 5 ng-5 μg, corresponding to 10-1000-fold reductions compared with traditional drug screening systems with 96-well or 384-well plates. The present work provides a novel and flexible droplet-based microfluidic approach for performing cell-based screening with complex and multistep operation procedures. PMID:23786644

  11. AtriplaR/anti-TB combination in TB/HIV patients. Drug in focus

    Directory of Open Access Journals (Sweden)

    Semvua Hadija H

    2011-11-01

    Full Text Available Abstract Background Co-administration of anti-tuberculosis and antiretroviral therapy is often inevitable in high-burden countries where tuberculosis is the most common opportunistic infection associated with HIV/AIDS. Concurrent use of rifampicin and several antiretroviral drugs is complicated by pharmacokinetic drug-drug interaction. Method Pubmed and Google search following the key words tuberculosis, HIV, emtricitabine, tenofovir efavirenz, interaction were used to find relevant information on each drug of the fixed dose combination AtriplaR Results Information on generic name, trade name, pharmacokinetic parameter, metabolism and the pharmacokinetic interaction with Anti-TB drugs of emtricitabine, tenofovir, and efavirenz was obtained. Conclusion Fixed dose combination of emtricitabine/tenofovir/efavirenz (ATRIPLAR which has been approved by Food and Drug Administration shows promising results as far as safety and efficacy is concerned in TB/HIV co-infection patients, hence can be considered effective and safe antiretroviral drug in TB/HIV management for adult and children above 3 years of age.

  12. Search algorithms as a framework for the optimization of drug combinations.

    Directory of Open Access Journals (Sweden)

    Diego Calzolari

    2008-12-01

    Full Text Available Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms -- originally developed for digital communication -- modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.

  13. Single-pill triple-combination therapy: an alternative to multiple-drug treatment of hypertension.

    Science.gov (United States)

    Chrysant, Steven G

    2011-11-01

    Hypertension (HTN) affects an estimated 76.4 million US adults. Despite improvements in blood pressure (BP) control rates and the availability of effective antihypertensive agents, only 50% of these individuals achieve BP control. It is now recognized that many patients will require ≥ 2 antihypertensive agents to achieve BP control. Both the current US and reappraisal of the 2007 European guidelines include dual-combination regimens among recommended treatments for initial HTN therapy. For patients requiring 3 drugs, the combination of agents with complementary mechanisms of action (ie, renin-angiotensin-aldosterone system blocker, calcium channel blocker, and diuretic) has been recognized as rational and effective. Three single-pill triple-drug combinations have recently been approved for use in HTN in the United States: valsartan (VAL)/amlodipine (AML)/hydrochlorothiazide (HCTZ); olmesartan medoxomil (OM)/AML/HCTZ; and aliskiren (ALI)/VAL/HCTZ. Triple-combination regimens have resulted in a greater proportion of patients achieving BP control compared with dual-combination regimens, with significantly lower BP levels documented after only 2 weeks at maximum doses. Single-pill combinations offer convenience to address barriers to BP control such as poor adherence to therapy and therapeutic inertia. Additional benefits of combining antihypertensive agents from different classes include improved efficacy, safety, and reduction of cardiovascular risk. In patients with essential HTN for whom dual therapy is inadequate, single-pill triple-drug therapy can offer a simplified and effective treatment strategy. PMID:22104451

  14. Analysis of combination drug therapy to develop regimens with shortened duration of treatment for tuberculosis.

    Directory of Open Access Journals (Sweden)

    George L Drusano

    Full Text Available Tuberculosis remains a worldwide problem, particularly with the advent of multi-drug resistance. Shortening therapy duration for Mycobacterium tuberculosis is a major goal, requiring generation of optimal kill rate and resistance-suppression. Combination therapy is required to attain the goal of shorter therapy.Our objective was to identify a method for identifying optimal combination chemotherapy. We developed a mathematical model for attaining this end. This is accomplished by identifying drug effect interaction (synergy, additivity, antagonism for susceptible organisms and subpopulations resistant to each drug in the combination.We studied the combination of linezolid plus rifampin in our hollow fiber infection model. We generated a fully parametric drug effect interaction mathematical model. The results were subjected to Monte Carlo simulation to extend the findings to a population of patients by accounting for between-patient variability in drug pharmacokinetics.All monotherapy allowed emergence of resistance over the first two weeks of the experiment. In combination, the interaction was additive for each population (susceptible and resistant. For a 600 mg/600 mg daily regimen of linezolid plus rifampin, we demonstrated that >50% of simulated subjects had eradicated the susceptible population by day 27 with the remaining organisms resistant to one or the other drug. Only 4% of patients had complete organism eradication by experiment end.These data strongly suggest that in order to achieve the goal of shortening therapy, the original regimen may need to be changed at one month to a regimen of two completely new agents with resistance mechanisms independent of the initial regimen. This hypothesis which arose from the analysis is immediately testable in a clinical trial.

  15. Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

    OpenAIRE

    Carlo Luca Romanò; Delia Romanò; Marco Lacerenza

    2012-01-01

    Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published p...

  16. Unlocking the Potential of High-Throughput Drug Combination Assays Using Acoustic Dispensing.

    Science.gov (United States)

    Chan, Grace Ka Yan; Wilson, Stacy; Schmidt, Stephen; Moffat, John G

    2016-02-01

    Assessment of synergistic effects of drug combinations in vitro is a critical part of anticancer drug research. However, the complexities of dosing and analyzing two drugs over the appropriate range of doses have generally led to compromises in experimental design that restrict the quality and robustness of the data. In particular, the use of a single dose response of combined drugs, rather than a full two-way matrix of varying doses, has predominated in higher-throughput studies. Acoustic dispensing unlocks the potential of high-throughput dose matrix analysis. We have developed acoustic dispensing protocols that enable compound synergy assays in a 384-well format. This experimental design is considerably more efficient and flexible with respect to time, reagent usage, and labware than is achievable using traditional serial-dilution approaches. Data analysis tools integrated in Genedata Screener were used to efficiently deconvolute the combination compound mapping scheme and calculate compound potency and synergy metrics. We have applied this workflow to evaluate interactions among drugs targeting different nodes of the mitogen-activated protein kinase pathway in a panel of cancer cell lines. PMID:26160862

  17. Combined therapy of irradiation and drug treatment in primary brain tumours

    International Nuclear Information System (INIS)

    Combinations of radiation - drug regimes in malignant brain tumours are not generally established. The reasons for their limited clinical use are due to the selective permeability of the blood/brain barrier to cytostatic drugs and the increased risk of acute and late effects by altered pathophysiology. Therefore, the effects of combined modality of radio- and chemotherapy in malignant neoplasms of the central nervous system such as malignant gliomas and medulloblastomas should be studied only in randomized trials. In spite of promising experimental results effective radiosensitizing agents are not available for clinical use. The biological response modifiers (Interferons, TNF, IL-2) are now introduced for clinical evaluations, but preliminary results postpone the hope for improvement the therapeutical results to following drug generations. (orig.)

  18. Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Koizumi, Yoshiki [School of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan; Nakajim, Syo [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Ohash, Hirofumi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J; Tanaka, Yasuhito [Department of Virology and Liver Unit, Nagoya City University Graduate School of Medicinal Sciences, Nagoya, Japan; Wakita, Takaji [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan; Perelson, Alan S. [Los Alamos National Laboratory; Iwami, Shingo [Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan: PRESTO, JST, Saitama, Japan: CREST, JST, Saitama, Japan; Watashi, Koichi [Department of Virology II, National Institute of Infectious Diseases, Tokyo, Japan: Department of Applied Biological Sciences, Faculty of Science and Technology, Tokyo University of Sciences, Chiba, J

    2016-03-21

    Cell culture study combing a mathematical model and computer simulation quantifies the anti-hepatitis C virus drug efficacy at any concentrations and any combinations in preclinical settings, and can obtain rich basic evidences for selecting optimal treatments prior to costly clinical trials.

  19. Treatment of Plasmodium chabaudi Parasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System

    OpenAIRE

    Zoraima Neto; Marta Machado; Ana Lindeza; Virgílio do Rosário; Gazarini, Marcos L.; Dinora Lopes

    2013-01-01

    Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed. In vivo...

  20. Spatiotemporally synchronized cancer combination therapy using photo-activated nanoparticle drug delivery systems (Conference Presentation)

    Science.gov (United States)

    Hasan, Tayyaba

    2016-03-01

    This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.

  1. Cost-effectiveness study of three antimalarial drug combinations in Tanzania.

    Directory of Open Access Journals (Sweden)

    Virginia Wiseman

    2006-10-01

    Full Text Available BACKGROUND: As a result of rising levels of drug resistance to conventional monotherapy, the World Health Organization (WHO and other international organisations have recommended that malaria endemic countries move to combination therapy, ideally with artemisinin-based combinations (ACTs. Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations. METHODS AND FINDINGS: An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO, used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ, AQ with sulfadoxine-pyrimethamine (AQ+SP, AQ with artesunate (AQ+AS, and artemether-lumefantrine (AL in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28. All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US1.70 dollars or a net saving of US22.40 dollars per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs, respectively, but this did not change the finding that AL and AQ+AS dominate monotherapy. CONCLUSIONS: In an area of high drug resistance, there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive, because they are significantly more effective than other options and therefore reduce the need for further treatment. This is

  2. Combination Drug Products for HIV-A Word of Caution for the Transplant Clinician.

    Science.gov (United States)

    Patel, S J; Kuten, S A; Musick, W L; Gaber, A O; Monsour, H P; Knight, R J

    2016-08-01

    Modern-day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed-dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV-infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction-induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat-containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV-positive transplant recipients and their providers. PMID:27089541

  3. Searching for disease-modifying drugs in AD: can we combine neuropsychological tools with biological markers?

    Science.gov (United States)

    Caraci, Filippo; Castellano, Sabrina; Salomone, Salvatore; Drago, Filippo; Bosco, Paolo; Di Nuovo, Santo

    2014-02-01

    Drug discovery efforts in Alzheimer's disease (AD) have been directed in the last ten years to develop "disease-modifying drugs" able to exert neuroprotective effects in an early phase of AD pathogenesis. Unfortunately several candidate disease-modifying drugs have failed in Phase III clinical trials conducted in mild to moderate AD for different methodological difficulties, such as the time course of treatment in relation to development of disease as well as the appropriate use of validated biological and neuropsychological markers. Mild cognitive impairment (MCI) has been considered a precursor of AD. Much effort is now directed to identify the most appropriate and sensitive markers which can predict the progression from MCI to AD, such as neuroimaging markers (e.g. hippocampal atrophy and amyloid positron emission tomography imaging), cerebrospinal fluid markers (i.e. association of elevated tau with low levels of amyloid β -peptide(1-42) and neuropsychological markers (i.e. episodic memory deficits and executive dysfunction). Recent studies demonstrate that the combination of these different biomarkers significantly increases the chance to predict the conversion into AD within 24 months. These biomarkers will be essential in the future to analyze clinical efficacy of disease-modifying drugs in MCI patients at high risk to develop AD. In the present review we analyze recent evidence on the combination of neuropsychological and biological markers in AD as a new tool to track disease progression in early AD as well as the response to disease-modifying drugs. PMID:24040795

  4. Efficacy evaluation of fluoxetine combined with conventional drug treatment on unstable angina patients complicated with depression

    Institute of Scientific and Technical Information of China (English)

    Chun-Hua Liao

    2015-01-01

    Objective:To study the efficacy of fluoxetine combined with conventional drug treatment on unstable angina patients complicated with depression. Methods:120 cases of unstable angina patients with depression were randomly divided into two groups. The anti-depression group received fluoxetine combined with conventional drug therapy; the conventional group received conventional drug therapy. Then contents of monoamine neurotransmitters and their metabolites, antioxidants and inflammatory mediators of both groups were compared. Results:Serum monoamine neurotransmitters NE, 5-HT and HA levels of the anti-depression group were higher than those of the conventional group and metabolites 5-HIAA and HVA contents were lower than those of the conventional group; serum SOD, CAT, GSH and HSP-70 contents of the anti-depression group were higher than those of the conventional group, and hs-CRP, MMP9, MCP1 and HMGB1 contents were lower than those of the conventional group. Conclusion:Fluoxetine combined with conventional drug therapy can increase the contents of monoamine neurotransmitters and antioxidants, and reduce oxidative stress response and inflammatory response; it is an ideal method for treating unstable angina complicated with depression.

  5. Overcoming Resistance of Cancer Cells to PARP-1 Inhibitors with Three Different Drug Combinations.

    Directory of Open Access Journals (Sweden)

    Michal Yalon

    Full Text Available Inhibitors of poly[ADP-ribose] polymerase 1 (PARPis show promise for treatment of cancers which lack capacity for homologous recombination repair (HRR. However, new therapeutic strategies are required in order to overcome innate and acquired resistance to these drugs and thus expand the array of cancers that could benefit from them. We show that human cancer cell lines which respond poorly to ABT-888 (a PARPi, become sensitive to it when co-treated with vorinostat (a histone deacetylase inhibitor (HDACi. Vorinostat also sensitized PARPis insensitive cancer cell lines to 6-thioguanine (6-TG-a drug that targets PARPis sensitive cells. The sensitizing effect of vorinostat was associated with increased phosphorylation of eukaryotic initiation factor (eIF 2α which in and of itself increases the sensitivity of cancer cells to ABT-888. Importantly, these drug combinations did not affect survival of normal fibroblasts and breast cells, and significantly increased the inhibition of xenograft tumor growth relative to each drug alone, without affecting the mice weight or their liver and kidney function. Our results show that combination of vorinostat and ABT-888 could potentially prove useful for treatment of cancer with innate resistance to PARPis due to active HRR machinery, while the combination of vorinostat and 6-TG could potentially overcome innate or acquired resistance to PARPis due to secondary or reversal BRCA mutations, to decreased PARP-1 level or to increased expression of multiple drug resistant proteins. Importantly, drugs which increase phosphorylation of eIF2α may mimic the sensitizing effect of vorinostat on cellular response to PARPis or to 6-TG, without activating all of its downstream effectors.

  6. Polymeric Nanoparticles Containing Combination Antiretroviral Drugs for HIV Type 1 Treatment

    OpenAIRE

    Shibata, Annemarie; McMullen, Emily; Pham, Alex; Belshan, Michael; Sanford, Bridget; ZHOU, YOU; Goede, Michael; Date, Abjijit A.; Destache, Christopher J.

    2013-01-01

    The use of combination antiretroviral nanoparticles (cART NPs) was investigated as a novel treatment approach for the inhibition of HIV-1 replication. We developed nanoparticles of biodegradable polymer, poly-(dl-lactide-co-glycolic acid; PLGA) containing efavirenz (EFV) and boosted lopinavir (lopinavir/ritonavir; LPV/r) by a high-pressure homogenization method. The method resulted in >79% drug entrapment efficiency for each of the three drugs. The average size of cART NPs was 138.3±55.4 nm a...

  7. Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT.

    Science.gov (United States)

    Gary-Bobo, Magali; Hocine, Ouahiba; Brevet, David; Maynadier, Marie; Raehm, Laurence; Richeter, Sébastien; Charasson, Virginie; Loock, Bernard; Morère, Alain; Maillard, Philippe; Garcia, Marcel; Durand, Jean-Olivier

    2012-02-28

    The synthesis of mesoporous silica nanoparticles (MSN) covalently encapsulating fluoresceine or a photosensitizer, functionalized with galactose on the surface is described. Confocal microscopy experiments demonstrated that the uptake of galactose-functionalized MSN by colorectal cancer cells was mediated by galactose receptors leading to the accumulation of the nanoparticles in the endosomal and lysosomal compartments. The MSN functionalized with a photosensitizer and galactose were loaded with the anti-cancer drug camptothecin. Those MSN combining drug delivery and photodynamic therapy were tested on three cancer cell lines and showed a dramatic enhancement of cancer cell death compared to separate treatments. PMID:22178618

  8. Experimental study of anti-inflammatory activity of the new combined with drug urolytolytic action

    Directory of Open Access Journals (Sweden)

    Iermolenko T.I.

    2015-06-01

    Full Text Available Herbal medicines provide their versatile complex influence on the course of the pathological process in the kidneys due to biologically active compounds. Specifically, they cause the direct impact on the concrements formation. The search of drugs which would contain high biological compounds of plant origin is an actual issue of modern pharmacology. The aim of investigation was to study the anti-inflammatory activity of the new combined drug of urolytolytic action, which includes the total plant extract and succinate buffer complex. Materials and methods: aseptic exudative inflammation was caused by subplantar introduction of 0,1 ml of 1% solution of λ-karahenin in the right hind paw of rats, the investigated drug was administered at doses 1, 2 and 4 ml/kg. The influence of the studied drug was evaluated in terms of swelling limbs volume. It is shown that the severity of antiexudative action of flarosukcine had dose-dependent nature, increasing from dose of 1,0 ml/kg to 2,0 ml/kg (by 5,5%. Further dose increase to 4,0 ml/kg, was not defined by significant increase of activity. Anti-inflammatory activity of the drug ranged from 25 to 33%, which can be regarded as quite distinct, since in pharmacological study of anti-inflammatory drugs pharmacological activity level of at least 20% is significant.

  9. Combination of Targeted Drugs to Control Chronic Lymphocytic Leukemia: Harnessing the Power of New Monoclonal Antibodies in Combination With Ibrutinib.

    Science.gov (United States)

    Cramer, Paula; Langerbeins, Petra; Hallek, Michael

    2016-01-01

    The landscape of treatment for chronic lymphocytic leukemia is rapidly changing at present. Considerable improvement has been achieved with the introduction of the anti-CD20 antibodies, and chemoimmunotherapy has now become an established standard for patients without the high-risk features del(17p)/TP53 mutation. Also, the outcome of patients with these adverse genetic aberrations was dramatically improved with the introduction of the kinase inhibitors ibrutinib and idelalisib. Different combinations of these and additional novel agents are currently evaluated in clinical trials. The combination of the Bruton tyrosine kinase inhibitor ibrutinib with an anti-CD20 antibody is an attractive option, because both drugs act synergistically: ibrutinib redistributes the CLL cells from their homing organs to the peripheral blood, and obinutuzumab eliminates the leukemic cells in the blood with particular efficiency. Adding the Bcl-2 antagonist venetoclax could further intensify the treatment of CLL. This combination might hold the potential to achieve a deep remission with an eradication of residual CLL cells and thus lead to long-term remissions of CLL. PMID:26841018

  10. Boceprevir in combination with HIV protease inhibitors in patients with advanced fibrosis-altered drug-drug interactions?

    Directory of Open Access Journals (Sweden)

    C Schwarze-Zander

    2012-11-01

    Full Text Available In HIV/HCV co-infected patients improved treatment outcomes have been reported for the HCV protease inhibitors (PIs boceprevir (BOC and telaprevir (TVR, reaching SVR rates of up to 70% in pilot trials. Due to complex drug-drug-interactions triple therapy is substantially limited in HIV/HCV-coinfected individuals. Co-administration of BOC with the commonly available HIV PIs has been reported not only to decrease the level of BOC but also to lead to relevant decreases in the respective HIV PI. Here, we report on two patients who received BOC-containing HCV triple therapy in combination with a HIV PI. Patient 1 was on darunavir 800 mg/ritonavir 100 mg once-daily mono-therapy. Using FibroScan a liver stiffness of 34 kPa suggested liver cirrhosis prior to start of HCV triple therapy. At week 5 of HCV triple therapy darunavir trough concentration was measured in the reference range with 3777 ng/ml (reference trough concentration 2400–4600 ng/ml. HCV-RNA became negative at week 10 and HIV-RNA was below detection limit (<40 copies/ml at all times. Patient 2 was on a simplified FTC qd and fos-amprenavir 700 mg/ritonavir 100 mg bid regimen. Liver disease had also progressed to liver cirrhosis, confirmed in FibroScan, with a liver stiffness of 32 kPa. At week 8 of HCV triple therapy fos-amprenavir trough level was measured in the normal reference range with 1699 ng/ml (reference trough concentration 750–2500 ng/ml. At week 11 HCV-RNA was <12 IU/ml and HIV viral load was below detection limit of <40 copies/ml at all times. Our clinical data suggest that in patients with advanced liver disease possibly drug levels of HIV PIs which are coadministered with BOC may be within the normal range. In order to better understand the true amount of drug interactions between BOC and commonly used HIV PIs in HIV/HCV-coinfected patients with more advanced liver fibrosis, urgently more PK studies are required to make HCV triple therapy accessible for a wider number of

  11. Observations on 52 Patients with Diabetic Peripheral Neuropathy Treated by Needling Combined with Drug

    Institute of Scientific and Technical Information of China (English)

    ZHENG Hui-tian; LI Yong-fang; YUAN Shun-xing; ZHANG Chen-guang; CHEN Guo-mei; ZHANG Li-fang

    2004-01-01

    To observe the clinical therapeutic effect of diabetic peripheral neuropathy (DPN) treated by needling combined with drug, 104 patients with DPN were randomly divided into acupuncture plus drug group and control group, and each group had 52 patients. After treatment of two months, the clinical effective rate in acupuncture plus drug group was 51.9%, and the total effective rate was 88.5%, both of them were better than those in control group (P<0.05). The needling method of nourishing the kidney and dredging the meridian combined with drug had good clinic effect in the treatment of DPN.%观察针药结合"补肾通络法"对糖尿病周围神经病变(DPN)的临床疗效.将DPN患者104例,随机分为针药组和对照组各52例.治疗2个月后,针药组的临床显效率为51.9%,总有效率为88.5%,均优于对照组(P<0.05).针药结合"补肾通络法"治疗DPN临床效果良好.

  12. Recycling Antibiotics into GUMBOS: A New Combination Strategy to Combat Multi-Drug-Resistant Bacteria

    Directory of Open Access Journals (Sweden)

    Marsha R. Cole

    2015-04-01

    Full Text Available The emergence of multi-drug-resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded β-lactam antibiotics (ampicillin, carbenicillin, cephalothin and oxacillin and a well-known antiseptic (chlorhexidine di-acetate were fashioned into a group of uniform materials based on organic salts (GUMBOS as an alternative to conventional combination drug dosing strategies. The antibacterial activity of precursor ions (e.g., chlorhexidine diacetate and β-lactam antibiotics, GUMBOS and their unreacted mixtures were studied with 25 clinical isolates with varying antibiotic resistance using a micro-broth dilution method. Acute cytotoxicity and therapeutic indices were determined using fibroblasts, endothelial and cervical cell lines. Intestinal permeability was predicted using a parallel artificial membrane permeability assay. GUMBOS formed from ineffective β-lactam antibiotics and cytotoxic chlorhexidine diacetate exhibited unique pharmacological properties and profound antibacterial activity at lower concentrations than the unreacted mixture of precursor ions at equivalent stoichiometry. Reduced cytotoxicity to invasive cell types commonly found in superficial and chronic wounds was also observed using GUMBOS. GUMBOS show promise as an alternative combination drug strategy for treating wound infections caused by drug-resistant bacteria.

  13. Combination Therapy Counteracts the Enhanced Transmission of Drug-Resistant Malaria Parasites to Mosquitoes

    OpenAIRE

    Hallett, Rachel L; Colin J Sutherland; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J.; Pinder, Margaret; Walraven, Gijs; Geoffrey A T Targett; Alloueche, Ali

    2004-01-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resi...

  14. Prescription pattern of fixed dose drug combination in cardiology department in a tertiary care hospital

    OpenAIRE

    Pramod Kumar Manjhi; Lalit Mohan; Manish Kumar; Harihar Dikshit; Singh, B. P.; Anuj Kumar Pathak; Sanjeev Kumar

    2016-01-01

    Background: A cardiovascular disease (CVD) is one of the most common causes of mortality and morbidity globally. The drastic change in the lifestyle of population during 21st century has had a great impact on health especially cardiovascular diseases. Objective of this study was to assess the prescription pattern of fixed dose drug combinations (FDCs) in the department of cardiology in a tertiary care hospital. Methods: The prescriptions of 210 patients suffered by cardiovascular disorders...

  15. Stability Enhancement of Drug Layered Pellets in a Fixed Dose Combination Tablet

    OpenAIRE

    Burke, Matthew D.; He, Xiaorong; Cook, Chris; Petrov, Greg A.; Long, Susan; Coffin, Mark D.

    2013-01-01

    The purpose of this research was to develop a stable fixed dose combination tablet for a model DPP-IV inhibitor and metformin hydrochloride. The dipeptidyl peptidase IV (DPP-IV) inhibitor was particularly challenging to formulate due to its significant chemical instability and moisture sensitivity. Various formulation strategies were investigated and placed on accelerated stability to determine the lead approach and critical quality attributes. The lead formulation investigated was a drug lay...

  16. Tall gastrodis tuber combined with antiepileptic drugs repairs abnormal perfusion foci in focal epilepsy

    Institute of Scientific and Technical Information of China (English)

    Weimin Wang; Zhenyu Fan; Yongqin Zhang; Yuxia Yang; Yaqing Liu; Xiaoli Dang; Wenjun Song; Yinping Wu; Jiang Ye

    2013-01-01

    One hundred patients with focal epilepsy were recruited for the present study and their seizures controlled with antiepileptic drugs. The patients then orally received a capsule of tall gastrodis tuber powder, a traditional Chinese drug, and underwent single photon emission computed tomography, long-term electroencephalogram, and CT/MRI. Blood drug levels were monitored throughout the study. Before treatment with tall gastrodis tuber, 35 of the 100 cases had abnormal CT/MRI scans; 79 cases had abnormal single photon emission computed tomography images; 86 cases had abnormal electroencephalogram; and a total of 146 abnormal perfusion foci were observed across the 100 subjects. After treatment, the number of patients with normal single photon emission computed tomography images increased by 12; normal electroencephalogram was observed in an additional 27 cases and the number of patients with epileptiform discharge decreased by 29 (34% of 86); the total number of abnormal perfusion foci decreased by 52 (36%) and changes in abnormal foci were visible in 65 patients. These changes indicate that the administration of tall gastrodis tuber in combination with antiepileptic drugs repairs abnormal perfusion foci in patients with focal epilepsy. Our results demonstrate that traditional Chinese drugs can repair abnormal perfusion foci and, as such, are a promising new pathway in the treatment of focal epilepsy.

  17. Antibody therapy alone and in combination with targeted drugs in chronic lymphocytic leukemia.

    Science.gov (United States)

    Robak, Tadeusz; Blonski, Jerzy Z; Robak, Pawel

    2016-04-01

    The development of non-chemotherapeutic agents, including monoclonal antibodies (mAbs) and other targeted drugs, makes chemotherapy-free treatment an attractive option for chronic lymphocytic leukemia (CLL). The classical mAb, rituximab, has been authorized for use in both first-line and second-line therapy for CLL. New mAbs directed against CD20, ofatumumab, and obinutuzumab (GA-101) have also been approved for the treatment of this disease. Recently, several new mAbs with potential benefits over the approved anti-CD20 antibodies have been developed for use in CLL. Anti-CD37, anti-CD19, and anti-CD40 mAbs are in early clinical trials and show promise in treating CLL. In addition, the combination of mAbs with B-cell receptor signaling pathway inhibitors and immunomodulatory drugs makes the chemotherapy-free option a reality today. Combinations of antibodies with targeted drugs like ibrutinib, idelalisib, or lenalidomide are expected to replace chemotherapy-based combinations for treating CLL in the near future. However, phase III trials should confirm the benefit of these new treatment strategies and establish their exact place in the therapeutic armamentarium for CLL. PMID:27040707

  18. Drug-drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data.

    Science.gov (United States)

    Natale, James J; Spinelli, Tulla; Calcagnile, Selma; Lanzarotti, Corinna; Rossi, Giorgia; Cox, David; Kashef, Kimia

    2016-06-01

    Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)-a new NK1 RA-and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. PMID:25998320

  19. Drug resistant falciparum malaria and the use of artesunate-based combinations : focus on clinical trials sponsored by TDR

    OpenAIRE

    Walter R.J. Taylor, Jean Rigal & Piero L. Olliaro

    2003-01-01

    Antimalarial drug resistance has now become a serious global challenge and is the principal reasonfor the decline in antimalarial drug efficacy. Malaria endemic countries need inexpensive and efficaciousdrugs. Preserving the life spans of antimalarial drugs is a key part of the strategy for rollingback malaria. Artemisinin-based combinations offer a new and potentially highly effective way tocounter drug resistance. Clinical trials conducted in African children have attested to the good toler...

  20. Restraint use and risky driving behaviors across drug types and drug and alcohol combinations for drivers involved in a fatal motor vehicle collision on U.S. roadways

    OpenAIRE

    Liu, Chang; Huang, Yanlan; Pressley, Joyce C.

    2016-01-01

    Background While driving impaired is a well-recognized risk factor for motor vehicle (MV) crash, recent trends in recreational drug use and abuse may pose increased threats to occupant safety. This study examines mechanisms through which drug and/or alcohol combinations contribute to fatal MV crash. Methods The Fatality Analysis Reporting System (FARS) for 2008–2013 was used to examine drugs, alcohol, driver restraint use, driver violations/errors and other behaviors of drivers of passenger v...

  1. Clinical toxicology of citalopram after acute intoxication with the sole drug or in combination with other drugs : overview of 26 cases

    NARCIS (Netherlands)

    Jimmink, Afra; Caminada, Klaartje; Hunfeld, Nicole G M; Touw, Daan J

    2008-01-01

    There is discussion concerning the cardiac safety of citalopram in an overdose. The aim of this study was to investigate the toxic effects and toxicokinetic parameters of citalopram in an overdose as a single drug and in combination with other drugs. Cases observed between 1997 and 2006 were evaluat

  2. Treatment of Plasmodium chabaudi Parasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System

    Directory of Open Access Journals (Sweden)

    Zoraima Neto

    2013-01-01

    Full Text Available Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS were analyzed. In vivo efficacy of curcumin was studied in BALB/c mice infected with Plasmodium chabaudi clones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs. Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group’s 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.

  3. Assessment of Malaria In Vitro Drug Combination Screening and Mixed-Strain Infections Using the Malaria Sybr Green I-Based Fluorescence Assay▿

    OpenAIRE

    Co, Edgie-Mark A.; Dennull, Richard A.; Reinbold, Drew D.; Waters, Norman C; Johnson, Jacob D.

    2009-01-01

    Several drug development strategies, including optimization of new antimalarial drug combinations, have been used to counter malaria drug resistance. We evaluated the malaria Sybr green I-based fluorescence (MSF) assay for its use in in vitro drug combination sensitivity assays. Drug combinations of previously published synergistic (atovaquone and proguanil), indifferent (chloroquine and azithromycin), and antagonistic (chloroquine and atovaquone) antimalarial drug interactions were tested ag...

  4. Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients

    OpenAIRE

    Li Jian; Zhu De-mei; Huang Jun; Liu Xiao-fang; Liang Wang; Zhang Jing

    2011-01-01

    Abstract Background Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB) strains. ...

  5. Combined traditional medicine and pharmacological antihypertensive drugs in a rural community of West Java, Indonesia

    Directory of Open Access Journals (Sweden)

    Bastaman Basuki

    2004-12-01

    Full Text Available Some hypertensive subjects in Indonesia consume traditional herbal medicines in addition to the usual pharmacological drugs. This paper studied the relationship between several traditional herbal medicines, such as morinda, star fruit, garlic, or jamu, believed to control hypertension and the risk of current pharmacological antihypertensive drug users in subjects with stage 1 and 2 hypertension in a rural community West Java, Indonesia. The data were obtained from 3 field studies by the second year medical students of the Faculty of Medicine, University of Indonesia conducted in 2001, 2002, and 2003 in a subdistrict of the Bogor regency. The subjects were selected randomly from neighborhood clusters. Interviews and blood pressure measurements were conducted at the houses of the subjects by specially trained second year medical students supervised by faculty members. There were 496 subjects with stage 1 or 2 hypertension, with 11.5% under current antihypertensive drugs. Compared with the hypertension stage 1 subjects, hypertension stage 2 subjects were 5.4 times more likely to be currently taking pharmacological antihypertensive medication (adjusted odds ratio = 5.44; 95% confidence interval = 2.64-11.27. The combined of current antihypertensive medication with traditional medicines were cucumber which being the most dominant followed by star fruit and morinda. Reasons for this were probably the strong influence of culture, the limited medical facilities, and high cost of the antihypertensive drugs. It was concluded that in a rural Indonesia, it was common for hypertensive subjects to take pharmacological drugs as well as traditional medicine for antihypertensive therapy. (Med J Indones 2004; 13: 246-51Keywords: hypertension, pharmacological drugs, traditional medicine, Indonesia

  6. Antineuropathic and Antinociceptive Drugs Combination in Patients with Chronic Low Back Pain: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Carlo Luca Romanò

    2012-01-01

    Full Text Available Purpose. Chronic low back pain (LBP is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy, with similar side effects.

  7. Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine)(10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells. (author)

  8. Combination therapy counteracts the enhanced transmission of drug-resistant malaria parasites to mosquitoes.

    Science.gov (United States)

    Hallett, Rachel L; Sutherland, Colin J; Alexander, Neal; Ord, Rosalynn; Jawara, Musa; Drakeley, Chris J; Pinder, Margaret; Walraven, Gijs; Targett, Geoffrey A T; Alloueche, Ali

    2004-10-01

    Malaria parasites carrying genes conferring resistance to antimalarials are thought to have a selective advantage which leads to higher rates of transmissibility from the drug-treated host. This is a likely mechanism for the increasing prevalence of parasites with resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine in sub-Saharan Africa. Combination therapy is the key strategy being implemented to reduce the impact of resistance, but its effect on the transmission of genetically resistant parasites from treated patients to mosquito vectors has not been measured directly. In a trial comparing CQ monotherapy to the combination CQ plus artesunate (AS) in Gambian children with uncomplicated falciparum malaria, we measured transmissibility by feeding Anopheles gambiae mosquitoes with blood from 43 gametocyte-positive patients through a membrane. In the CQ-treated group, gametocytes from patients carrying parasites with the CQ resistance-associated allele pfcrt-76T prior to treatment produced infected mosquitoes with 38 times higher Plasmodium falciparum oocyst burdens than mosquitoes fed on gametocytes from patients infected with sensitive parasites (P < 0.001). Gametocytes from parasites carrying the resistance-associated allele pfmdr1-86Y produced 14-fold higher oocyst burdens than gametocytes from patients infected with sensitive parasites (P = 0.011). However, parasites carrying either of these resistance-associated alleles pretreatment were not associated with higher mosquito oocyst burdens in the CQ-AS-treated group. Thus, combination therapy overcomes the transmission advantage enjoyed by drug-resistant parasites. PMID:15388456

  9. A dual-targeting drug co-delivery system for tumor chemo- and gene combined therapy.

    Science.gov (United States)

    Zhang, Fangrong; Li, Min; Su, Yujie; Zhou, Jianping; Wang, Wei

    2016-07-01

    Regulation of gene expression using p53 is a promising strategy for treatment of numerous cancers, and chemotherapeutic drug dichloroacetate (DCA) induces apoptosis and growth inhibition in tumor, without apparent toxicity in normal tissues. Combining DCA and p53 gene could be an effective way to treat tumors. The progress towards broad applications of DCA/p53 combination requires the development of safe and efficient vectors that target to specific cells. In this study, we developed a DSPE-PEG-AA (1,2-distearoryl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol-2000)] ammonium salt-anisamide) modified reconstituted high-density lipoprotein-based DCA/p53-loaded nanoparticles (DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes), which was fabricated as a drug/gene dual-targeting co-delivery system for potential cancer therapy. Here, DCA-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL and to act as an antitumor drug to inhibit tumor cell growth. The DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge and low cytotoxicity for normal cells in vitro. The results of confocal laser scanning microscopy (CLSM) and flow cytometry confirmed that the scavenger receptor class B type I (SR-BI) and sigma receptor mediated dual-targeting function of the complexes inducing efficient cytoplasmic drug delivery and gene transfection in human lung adenocarcinoma cell line A549. And in vivo investigation on nude mice bearing A549 tumor xenografts revealed that DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes possessed specific tumor targeting and strong antitumor activity. The work described here demonstrated that the DSPE-PEG-AA/rHDL/DCA-PEI/p53 complexes might offer a promising tool for effective cancer therapy. PMID:27127046

  10. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

    Directory of Open Access Journals (Sweden)

    Wang ZY

    2015-03-01

    Full Text Available Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug–drug interactions (DDIs when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.Methods: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.Results: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John’s wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C>A, species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump

  11. New Mouse Models to Investigate the Efficacy of Drug Combinations in Human Chronic Myeloid Leukemia.

    Science.gov (United States)

    Lin, Hanyang; Woolfson, Adrian; Jiang, Xiaoyan

    2016-01-01

    Chronic myeloid leukemia (CML) comprises a simple and effective paradigm for generating new insights into the cellular origin, pathogenesis, and treatment of many types of human cancer. In particular, mouse models of CML have greatly facilitated the understanding of the underlying molecular mechanisms and pathogenesis of this disease and have led to the identification of new drug targets that in some cases offer the possibility of functional cure. There are currently three established CML mouse models: the BCR-ABL transgenic model, the BCR-ABL retroviral transduction/transplantation model, and the xenotransplant immunodeficient model. Each has its own unique advantages and disadvantages. Depending on the question of interest, some models may be more appropriate than others. In this chapter, we describe a newly developed xenotransplant mouse model to determine the efficacy of novel therapeutic agents, either alone or in combination. The model facilitates the evaluation of the frequency of leukemic stem cells with long-term leukemia-initiating activity, a critical subcellular population that causes disease relapse and progression, through the utilization of primary CD34(+) CML stem/progenitor cells obtained from CML patients at diagnosis and prior to drug treatment. We have also investigated the effectiveness of new combination treatment strategies designed to prevent the development of leukemia in vivo using BCR-ABL (+) blast crisis cells as a model system. These types of in vivo studies are important for the prediction of individual patient responses to drug therapy, and have the potential to facilitate the design of personalized combination therapy strategies. PMID:27581149

  12. Metformin Exhibits Radiation Countermeasures Efficacy When Used Alone or in Combination with Sulfhydryl Containing Drugs

    OpenAIRE

    Miller, Richard C.; Murley, Jeffrey S.; David J Grdina

    2014-01-01

    Metformin, a biguanide drug used in the treatment of type II diabetes, was evaluated alone and in combination with amifostine, captopril, MESNA or N-acetyl-cysteine (NAC) for its ability to protect when administered 24 h after irradiation. Mouse embryo fibroblasts (MEF), human microvascular endothelial cells (HMEC) and SA-NH mouse sarcoma cells were exposed to 4 Gy in vitro. C3H mice were exposed to 7 Gy and evaluated utilizing an endogenous spleen colony assay system. Amifostine and WR1065, ...

  13. Evaluation on the Use of Afatinib Alone or Combined with Other Drugs in Clinical Trials

    Institute of Scientific and Technical Information of China (English)

    LIU Lian-ke; SHU Yong-qian

    2016-01-01

    Afatinib, an oral tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER-2) and HER4, has been approved in treating patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Additionally, it also has efifcacy in other tumors. Currently, the recommended dose of afatinib is 40 mg once daily, but in clinical trials, the other doses are also used. This article mainly summarized the usage of afatinib alone or combined with other drugs in clinical trials, hoping to provide a better treatment reference for its clinical application.

  14. Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

    OpenAIRE

    K. Zwingenberger; J. A. Nogueira Queiroz; U. Poggensee; J. E. Alencar; J. Valdegunas; F. Esmeralda; Feldmeier, H.

    1987-01-01

    A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) against either agent, oxamniquine (15 mg/kg) or praziquantel (40 mg/kg) alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides) and MIF tec...

  15. Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field.

    Science.gov (United States)

    Kampinga, Harm H

    2006-05-01

    Hyperthermia results in protein unfolding that, if not properly chaperoned by Heat Shock Proteins (HSP), can lead to irreversible and toxic protein aggregates. Elevating HSP prior to heating makes cells thermotolerant. Hyperthermia also can enhance the sensitivity of cells to radiation and drugs. This sensitization to drugs or radiation is not directly related to altered HSP expression. However, altering HSP expression before heat and radiation or drug treatment will affect the extent of thermal sensitization because the HSP will attenuate the heat-induced protein damage that is responsible for radiation- or drug-sensitization. For thermal radiosensitization, nuclear protein damage is considered to be responsible for hyperthermic effects on DNA repair, in particular base excision repair. Hyperthermic drug sensitization can be seen for a number of anti-cancer drugs, especially of alkylating agents. Synergy between heat and drugs may arise from multiple events such as heat damage to ABC transporters (drug accumulation), intra-cellular drug detoxification pathways and repair of drug-induced DNA adducts. This may be why cells with acquired drug resistance (often multi-factorial) can be made responsive to drugs again by combining the drug treatment with heat. PMID:16754338

  16. Activity of oxantel pamoate monotherapy and combination chemotherapy against Trichuris muris and hookworms: revival of an old drug.

    Directory of Open Access Journals (Sweden)

    Jennifer Keiser

    Full Text Available 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

  17. Different combination of drugs regarding the damage on organs targeting salt sensitivity or non-salt-sensitive hypertension

    Institute of Scientific and Technical Information of China (English)

    吴琪

    2013-01-01

    Objective To study the damage on organs from salt sensitivity hypertension or non-salt-sensitive hypertension and the selection of drug combination.Methods 120 hypertensive patients including 60 cases salt-sensitive(SS)

  18. Susceptibility of Staphylococcus aureus Clinical Isolates to Propolis Extract Alone or in Combination with Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Mieczysław Sajewicz

    2013-08-01

    Full Text Available The objective of this study was to assess in vitro the antimicrobial activity of ethanolic extract of Polish propolis (EEPP against methicillin-sensitive Staphylococcus aureus (MSSA and methicillin-resistant Staphylococcus aureus (MRSA clinical isolates. The combined effect of EEPP and 10 selected antistaphylococcal drugs on S. aureus clinical cultures was also investigated. EEPP composition was analyzed by a High Performance Liquid Chromatography (HPLC method. The flavonoid compounds identified in Polish Propolis included flavones, flavonones, flavonolols, flavonols and phenolic acids. EEPP displayed varying effectiveness against twelve S. aureus strains, with minimal inhibitory concentration (MIC within the range from 0.39 to 0.78 mg/mL, determined by broth microdilution method. The average MIC was 0.54 ± 0.22 mg/mL, while calculated MIC50 and MIC90 were 0.39 mg/mL and 0.78 mg/mL, respectively. The minimum bactericidal concentration (MBC of the EEPP ranged from 0.78 to 3.13 mg/mL. The in vitro combined effect of EEPP and 10 antibacterial drugs was investigated using disk diffusion method-based assay. Addition of EEPP to cefoxitin (FOX, clindamycin (DA, tetracycline (TE, tobramycin (TOB, linezolid (LIN, trimethoprim+sulfamethoxazole (SXT, penicillin (P, erythromycin (E regimen, yielded stronger, cumulative antimicrobial effect, against all tested S. aureus strains than EEPP and chemotherapeutics alone. In the case of ciprofloxacin (CIP and chloramphenicol (C no synergism with EEPP was observed.

  19. Rational combination treatment with histone deacetylase inhibitors and immunomodulatory drugs in multiple myeloma

    International Nuclear Information System (INIS)

    Immunomodulatory drugs (IMiDs) thalidomide, lenalidomide (Len) and pomalidomide trigger anti-tumor activities in multiple myeloma (MM) by targetting cereblon and thereby impacting IZF1/3, c-Myc and IRF4. Histone deacetylase inhibitors (HDACi) also downregulate c-Myc. We therefore determined whether IMiDs with HDACi trigger significant MM cell growth inhibition by inhibiting or downregulating c-Myc. Combination treatment of Len with non-selective HDACi suberoylanilide hydroxamic acid or class-I HDAC-selective inhibitor MS275 induces synergic cytotoxicity, associated with downregulation of c-Myc. Unexpectedly, we observed that decreased levels of cereblon (CRBN), a primary target protein of IMiDs, was triggered by these agents. Indeed, sequential treatment of MM cells with MS275 followed by Len shows less efficacy than simultaneous treatment with this combination. Importantly ACY1215, an HDAC6 inhibitor with minimal effects on class-I HDACs, together with Len induces synergistic MM cytotoxicity without alteration of CRBN expression. Our results showed that only modest class-I HDAC inhibition is able to induce synergistic MM cytotoxicity in combination with Len. These studies may provide the framework for utilizing HDACi in combination with Len to both avoid CRBN downregulation and enhance anti-MM activities

  20. The challenges of changing national malaria drug policy to artemisinin-based combinations in Kenya

    Directory of Open Access Journals (Sweden)

    Otieno Dorothy N

    2007-05-01

    Full Text Available Abstract Backgound Sulphadoxine/sulphalene-pyrimethamine (SP was adopted in Kenya as first line therapeutic for uncomplicated malaria in 1998. By the second half of 2003, there was convincing evidence that SP was failing and had to be replaced. Despite several descriptive investigations of policy change and implementation when countries moved from chloroquine to SP, the different constraints of moving to artemisinin-based combination therapy (ACT in Africa are less well documented. Methods A narrative description of the process of anti-malarial drug policy change, financing and implementation in Kenya is assembled from discussions with stakeholders, reports, newspaper articles, minutes of meetings and email correspondence between actors in the policy change process. The narrative has been structured to capture the timing of events, the difficulties and hurdles faced and the resolutions reached to the final implementation of a new treatment policy. Results Following a recognition that SP was failing there was a rapid technical appraisal of available data and replacement options resulting in a decision to adopt artemether-lumefantrine (AL as the recommended first-line therapy in Kenya, announced in April 2004. Funding requirements were approved by the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM and over 60 million US$ were agreed in principle in July 2004 to procure AL and implement the policy change. AL arrived in Kenya in May 2006, distribution to health facilities began in July 2006 coincidental with cascade in-service training in the revised national guidelines. Both training and drug distribution were almost complete by the end of 2006. The article examines why it took over 32 months from announcing a drug policy change to completing early implementation. Reasons included: lack of clarity on sustainable financing of an expensive therapeutic for a common disease, a delay in release of funding, a lack of comparative efficacy data

  1. The combination regimen of idarubicin and taxotere is effective against human drug-resistant leukemic cell lines.

    Science.gov (United States)

    Majlessipour, F; Avramis, I A; Kwock, R; Weinberg, K I; Avrami, V I

    2002-01-01

    Up-regulation of Bcl-2 protein may contribute to drug resistance, by decreasing apoptosis after treatment, in pre-B and B-cell leukemias in pediatric patients. By contrast, augmented caspase-3 activity, an effector caspase, may be indicative of drug sensitivity due to increased cellular apoptosis. We have reported the development of an in vitro human T-lymphoblastic leukemia model resistant to ara-C and/or native E. coli L-asparaginase (ASNase), mimicking the drug resistance to the Capizzi II regimen. We have investigated the potential drug synergism between Idarubicin (IDA) and Taxotere (TXR) that may be active in the ara-C and ASNase double drug-resistant cell lines. The additive or synergistic activity between IDA and TXR is drug concentration-dependent in inducing caspase-3 activation and cellular apoptosis. We exposed two human drug-resistant cell lines that do not express the MDRI phenotype, one resistant to ASNase alone (CEM/ASNase-1-3) and the other resistant to both ara-C and ASNase (CEM/ara-C/I/ASNase-0.5-2), to physiologically achievable concentrations of IDA, TXR, or their combination. Both lines showed either synergistic drug activity to the combination regimen in comparison to either drug used alone, as determined by MTT assay, or additivity as demonstrated by flow cytometry after Annexin V and propidium iodide (PI) staining. After exposure of the ASNase-resistant line to various concentrations, the intracellular levels of Bcl-2 protein decreased to near zero relative to untreated control cells. The Bcl-2 protein reductions in these cells ranged from 30% to <1%, 49% to <1%, and 27% to 3% when treated with IDA or TXR as a single drug or IDA + TXR combination, respectively. Similarly, intracellular Bcl-2 levels in the double-resistant cell line decreased with reductions ranging from 24% to <1%, 87% to <1%, and 46% to <1% of the untreated control after treatment with IDA, TXR, or their combination, respectively. Conversely, the caspase-3 activity

  2. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  3. Network target for screening synergistic drug combinations with application to traditional Chinese medicine

    Directory of Open Access Journals (Sweden)

    Zhang Ningbo

    2011-06-01

    Full Text Available Abstract Background Multicomponent therapeutics offer bright prospects for the control of complex diseases in a synergistic manner. However, finding ways to screen the synergistic combinations from numerous pharmacological agents is still an ongoing challenge. Results In this work, we proposed for the first time a “network target”-based paradigm instead of the traditional "single target"-based paradigm for virtual screening and established an algorithm termed NIMS (Network target-based Identification of Multicomponent Synergy to prioritize synergistic agent combinations in a high throughput way. NIMS treats a disease-specific biological network as a therapeutic target and assumes that the relationship among agents can be transferred to network interactions among the molecular level entities (targets or responsive gene products of agents. Then, two parameters in NIMS, Topology Score and Agent Score, are created to evaluate the synergistic relationship between each given agent combinations. Taking the empirical multicomponent system traditional Chinese medicine (TCM as an illustrative case, we applied NIMS to prioritize synergistic agent pairs from 63 agents on a pathological process instanced by angiogenesis. The NIMS outputs can not only recover five known synergistic agent pairs, but also obtain experimental verification for synergistic candidates combined with, for example, a herbal ingredient Sinomenine, which outperforms the meet/min method. The robustness of NIMS was also showed regarding the background networks, agent genes and topological parameters, respectively. Finally, we characterized the potential mechanisms of multicomponent synergy from a network target perspective. Conclusions NIMS is a first-step computational approach towards identification of synergistic drug combinations at the molecular level. The network target-based approaches may adjust current virtual screen mode and provide a systematic paradigm for facilitating the

  4. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    Science.gov (United States)

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2013-01-01

    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  5. Torsadogenic risk of antipsychotics: combining adverse event reports with drug utilization data across Europe.

    Directory of Open Access Journals (Sweden)

    Emanuel Raschi

    Full Text Available BACKGROUND: Antipsychotics (APs have been associated with risk of torsade de Pointes (TdP. This has important public health implications. Therefore, (a we exploited the public FDA Adverse Event Reporting System (FAERS to characterize their torsadogenic profile; (b we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. METHODS: FAERS data (2004-2010 were analyzed based on the following criteria: (1 ≥ 4 cases of TdP/QT abnormalities; (2 Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers; (3 ≥ 4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD; (4 Significant ROR for VA/SCD; (5 Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled to group E (unclear/uncertain signal: only 2/5 criteria. Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID. RESULTS: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone. In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia to 13.99 (France, 2009. Considerable increment of Group A agents was found in several Countries (+3.47 in France: the exposure to olanzapine increased across all Countries (+1.84 in France and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009. Among Group B drugs, levomepromazine peaked 3.78 (Serbia; fluphenazine 1.61 (Slovenia. CONCLUSIONS: This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  6. Increasing Access to Subsidized Artemisinin-based Combination Therapy through Accredited Drug Dispensing Outlets in Tanzania

    Directory of Open Access Journals (Sweden)

    Gabra Michael

    2011-06-01

    Full Text Available Abstract Background In Tanzania, many people seek malaria treatment from retail drug sellers. The National Malaria Control Program identified the accredited drug dispensing outlet (ADDO program as a private sector mechanism to supplement the distribution of subsidized artemisinin-based combination therapies (ACTs from public facilities and increase access to the first-line antimalarial in rural and underserved areas. The ADDO program strengthens private sector pharmaceutical services by improving regulatory and supervisory support, dispenser training, and record keeping practices. Methods The government's pilot program made subsidized ACTs available through ADDOs in 10 districts in the Morogoro and Ruvuma regions, covering about 2.9 million people. The program established a supply of subsidized ACTs, created a price system with a cost recovery plan, developed a plan to distribute the subsidized products to the ADDOs, trained dispensers, and strengthened the adverse drug reactions reporting system. As part of the evaluation, 448 ADDO dispensers brought their records to central locations for analysis, representing nearly 70% of ADDOs operating in the two regions. ADDO drug register data were available from July 2007-June 2008 for Morogoro and from July 2007-September 2008 for Ruvuma. This intervention was implemented from 2007-2008. Results During the pilot, over 300,000 people received treatment for malaria at the 448 ADDOs. The percentage of ADDOs that dispensed at least one course of ACT rose from 26.2% during July-September 2007 to 72.6% during April-June 2008. The number of malaria patients treated with ACTs gradually increased after the start of the pilot, while the use of non-ACT antimalarials declined; ACTs went from 3% of all antimalarials sold in July 2007 to 26% in June 2008. District-specific data showed substantial variation among the districts in ACT uptake through ADDOs, ranging from ACTs representing 10% of all antimalarial sales

  7. Contribution of radiotherapy to the treatment of malignant tumors, 3. Combined drugs and radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Niibe, Hideo; Takahashi, Iku; Tamaki, Yoshio (Gunma Univ., Maebashi (Japan). School of Medicine)

    1984-09-01

    Effects of cytotoxic agent, hormone, hypoxic cell sensitizer, and radiation protector combined with radiation therapy in cancer management were analysed. The results were as follows: 1) An increase in response was seen in 25% or more of tumor nodules given radiotherapy combined with misonidazole, anoxic cell sensitizer, compared with radiotherpy alone. But the drug was also found to be neurotoxic and peripheral neuropathy. 2) Evidence has been given that Amifostine may protect the mucosal damage from radiation when Amifostine prior to irradiation was administrated to patients with tumor in the head and neck or in the pelvis. 3) There were no difference between five year survival of radiotherapy alone and with chemotherapy for patients with stage I Non-Hodgkin lymphoma. Chemotherapy following radiotherapy for patients with stage II was more effective treatment method than radiotherapy alone. 4) Radiotherapy for patients with prostate cancer was performed to control only primary site. The success rates of local control were over 80%. The near future holds extensive promise for a combination of radiation therapy, cytotoxic chemotherapy, hormone therapy, hypoxic cell sensitizer, and radiation protectors. All of these when used in the appropriate circumstances may yield significant improvements in the therapeutic ratio and in the long-tern control of tumors.

  8. Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

    Directory of Open Access Journals (Sweden)

    K. Zwingenberger

    1987-10-01

    Full Text Available A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg plus praziquantel (20 mg/kg against either agent, oxamniquine (15 mg/kg or praziquantel (40 mg/kg alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides and MIF technique (one gram of stool The achieved cure rates, as defined by absence of S. mansoni eggs in the faeces of individual patients at all points during the parasitological follow-up, were 81.8%, 81.2% and 67.6% for praziquantel, oxamniquine and the combination respectively. The reduction of eggs excretion in non cured patients six months after therapy ranged from 93.8-96.8% with praziquantel, 32.5-97% with oxamniquine and 76.9-99.5% with the combination. It is concluded that, at the used dosages, the three therapeutical regimens give similar and satisfactory results in the treatment of uncomplicated S. mansoni infection in Brazil.

  9. Prediction of Candidate Drugs for Treating Pancreatic Cancer by Using a Combined Approach

    OpenAIRE

    Ma, Yanfen; Hu, Jian; Zhang, Ning; Dong, Xinran; Li, Ying; Yang, Bo; Tian, Weidong; Wang, Xiaoqin

    2016-01-01

    Pancreatic cancer is the leading cause of death from solid malignancies worldwide. Currently, gemcitabine is the only drug approved for treating pancreatic cancer. Developing new therapeutic drugs for this disease is, therefore, an urgent need. The C-Map project has provided a wealth of gene expression data that can be mined for repositioning drugs, a promising approach to new drug discovery. Typically, a drug is considered potentially useful for treating a disease if the drug-induced differe...

  10. Improving Drug Loading of Mucosal Solvent Cast Films Using a Combination of Hydrophilic Polymers with Amoxicillin and Paracetamol as Model Drugs

    Directory of Open Access Journals (Sweden)

    Joshua Boateng

    2013-01-01

    Full Text Available Solvent cast mucosal films with improved drug loading have been developed by combining carboxymethyl cellulose (CMC, sodium alginate (SA, and carrageenan (CAR using paracetamol and amoxicillin as model drugs and glycerol (GLY as plasticizer. Films were characterized using X-ray powder diffraction (XRPD, scanning electron microscopy (SEM, folding resilience, swelling capacity, mucoadhesivity, and drug dissolution studies. SA, CMC, and GLY (5 : 3 : 6 films showed maximum amoxicillin loading of 26.3% whilst CAR, CMC, and GLY (1 : 2 : 3 films had a maximum paracetamol loading of 40%. XRPD analysis showed different physical forms of the drugs depending on the amount loaded. Films containing 29.4% paracetamol and 26.3% amoxicillin showed molecular dispersion of the drugs while excess paracetamol was observed on the film surface when the maximum 40% was loaded. Work of adhesion was similar for blank films with slightly higher cohesiveness for CAR and CMC based films, but the differences were significant between paracetamol and amoxicillin containing films. The stickiness and cohesiveness for drug loaded films were generally similar with no significant differences. The maximum percentage cumulative drug release was 84.65% and 70.59% for paracetamol and amoxicillin, respectively, with anomalous case two transport mechanism involving both drug diffusion and polymer erosion.

  11. Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs

    Directory of Open Access Journals (Sweden)

    Vreeke Ed

    2007-07-01

    Full Text Available Abstract Background Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs, the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. Methods The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe. From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Results Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1–1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum. There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania. Conclusion Additional studies are required to build a more robust methodology, and to assess current consumptions

  12. EFFECTIVENESS OF FIXED DRUG COMBINATION ANTI-RETROVIRAL THERAPY IN HIV INFECTED CHILDREN: AN EXPLORATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Somasekhar Rao

    2015-10-01

    Full Text Available Over 90 per cent of HIV infected babies were born to HIV positive mothers in Sub-Saharan Africa and worldwide. It is estimated that currently 2.3 million i.e 5.9% are children less than 15 yrs of age infected with HIV. Worldwide, children under age 15 who were newly infected with HIV, more than 90 percent were babies were born to HIV-positive women. An estimated 1500 children get newly infected with HIV each day globally. The scenario is similar at home in Andhra Pradesh, India. This present exploratory study is to find out the effectiveness of fixed drug combination of antiretroviral therapy in children. The results are encouraging and are similar to results from such studies elsewhere.

  13. Forty-seven Cases of Gonitis Treated by A Combined Therapy of Chinese Drugs and Acupuncture

    Institute of Scientific and Technical Information of China (English)

    杨文鹤

    2001-01-01

    @@Osteoarthritis, a nonspecific inflammatory lesion, is a commonly seen joint disease. Clinically, it is mainly characterized by arthralgia, swelling, and motor impairment. Since the knee joint is the load-bearing joint of the human body, and is susceptible to trauma, gonitis tends to have the highest morbidity in the four limbs, which manifests itself arthritis of patella and femur at the early stage; narrowness or disappearance of the medial joint space at the mid stage; and damage of the cartilage accompanied with flexion deformity at the late stage. In recent years, based on the experience of Prof. Cao Yiming, the author has treated 47 cases of gonitis by combined use of Chinese drugs and acupuncture, and obtained satisfactory therapeutic results as reported in the following.

  14. Use of homeopathic drugs in combination with fertilizers for the control of root rot fungi

    International Nuclear Information System (INIS)

    This study was conducted to evaluate the fungicidal effectiveness of homeopathic drugs in combination with fertilizers on the growth production and controlling of root rot fungi. Seeds treated with homeopathic drugs in addition of phosphorous and nitrogen fertilizers as soil amendment showed significant inhibitory effect on fungal growth as well as improved the plant growth. Remarkable control of root infecting fungi was shown by the seeds treated with Thuja occidentalis and Arnica montana at rate of 75 percentage v/v concentration and soil amended with urea at rate of 0.1 percentage w/w but greater increased in plant growth was observed by urea at rate of 0.01 percentage in the tested plants viz. mung bean, mash bean, sunflower and okra. Whereas, when A. montana and T. occidentalis at rate of 75 percentage v/v concentration along with the addition of DAP at rate of 0.01 and 0.1 percentage w/w respectively showed maximum suppression of Fusarium spp, R. solani and M. phaseolina and enhanced the plant height and weight followed by A. montana and T. occidentalis at rate of 50 percentage v/v concentration respectively showed a maximum control of root rot fungi and also strengthened the crop plant for better growth. (author)

  15. Combining Metabolite-Based Pharmacophores with Bayesian Machine Learning Models for Mycobacterium tuberculosis Drug Discovery

    Science.gov (United States)

    Sarker, Malabika; Li, Shao-Gang; Mittal, Nisha; Kumar, Pradeep; Wang, Xin; Stratton, Thomas P.; Zimmerman, Matthew; Talcott, Carolyn; Bourbon, Pauline; Travers, Mike; Yadav, Maneesh

    2015-01-01

    Integrated computational approaches for Mycobacterium tuberculosis (Mtb) are useful to identify new molecules that could lead to future tuberculosis (TB) drugs. Our approach uses information derived from the TBCyc pathway and genome database, the Collaborative Drug Discovery TB database combined with 3D pharmacophores and dual event Bayesian models of whole-cell activity and lack of cytotoxicity. We have prioritized a large number of molecules that may act as mimics of substrates and metabolites in the TB metabolome. We computationally searched over 200,000 commercial molecules using 66 pharmacophores based on substrates and metabolites from Mtb and further filtering with Bayesian models. We ultimately tested 110 compounds in vitro that resulted in two compounds of interest, BAS 04912643 and BAS 00623753 (MIC of 2.5 and 5 μg/mL, respectively). These molecules were used as a starting point for hit-to-lead optimization. The most promising class proved to be the quinoxaline di-N-oxides, evidenced by transcriptional profiling to induce mRNA level perturbations most closely resembling known protonophores. One of these, SRI58 exhibited an MIC = 1.25 μg/mL versus Mtb and a CC50 in Vero cells of >40 μg/mL, while featuring fair Caco-2 A-B permeability (2.3 x 10−6 cm/s), kinetic solubility (125 μM at pH 7.4 in PBS) and mouse metabolic stability (63.6% remaining after 1 h incubation with mouse liver microsomes). Despite demonstration of how a combined bioinformatics/cheminformatics approach afforded a small molecule with promising in vitro profiles, we found that SRI58 did not exhibit quantifiable blood levels in mice. PMID:26517557

  16. Landscape of Targeted Anti-Cancer Drug Synergies in Melanoma Identifies a Novel BRAF-VEGFR/PDGFR Combination Treatment.

    Directory of Open Access Journals (Sweden)

    Adam A Friedman

    Full Text Available A newer generation of anti-cancer drugs targeting underlying somatic genetic driver events have resulted in high single-agent or single-pathway response rates in selected patients, but few patients achieve complete responses and a sizeable fraction of patients relapse within a year. Thus, there is a pressing need for identification of combinations of targeted agents which induce more complete responses and prevent disease progression. We describe the results of a combination screen of an unprecedented scale in mammalian cells performed using a collection of targeted, clinically tractable agents across a large panel of melanoma cell lines. We find that even the most synergistic drug pairs are effective only in a discrete number of cell lines, underlying a strong context dependency for synergy, with strong, widespread synergies often corresponding to non-specific or off-target drug effects such as multidrug resistance protein 1 (MDR1 transporter inhibition. We identified drugs sensitizing cell lines that are BRAFV600E mutant but intrinsically resistant to BRAF inhibitor PLX4720, including the vascular endothelial growth factor receptor/kinase insert domain receptor (VEGFR/KDR and platelet derived growth factor receptor (PDGFR family inhibitor cediranib. The combination of cediranib and PLX4720 induced apoptosis in vitro and tumor regression in animal models. This synergistic interaction is likely due to engagement of multiple receptor tyrosine kinases (RTKs, demonstrating the potential of drug- rather than gene-specific combination discovery approaches. Patients with elevated biopsy KDR expression showed decreased progression free survival in trials of mitogen-activated protein kinase (MAPK kinase pathway inhibitors. Thus, high-throughput unbiased screening of targeted drug combinations, with appropriate library selection and mechanistic follow-up, can yield clinically-actionable drug combinations.

  17. Infectious complications in patients with multiple myeloma treated with new drug combinations containing thalidomide.

    Science.gov (United States)

    Offidani, Massimo; Corvatta, Laura; Polloni, Claudia; Gentili, Silvia; Brioni, Annamaria; Visani, Giuseppe; Galieni, Piero; Brunori, Marino; Alesiani, Francesco; Catarini, Massimo; Centurioni, Riccardo; Samori, Arduino; Blasi, Nicola; Ferranti, Mario; Fraticelli, Paolo; Mele, Anna; Rizzi, Rita; Larocca, Federica; Leoni, Pietro

    2011-05-01

    The literature provides scant data concerning infectious complications and their effect on the outcome of patients with multiple myeloma (MM) treated with new drug combinations. Despite no substantial myelotoxic effect, thalidomide increases the risk of severe infections in patients with MM. We studied 202 patients who received regimens containing thalidomide in order to assess the time, type, outcome, and factors affecting development of severe infections, role of antibiotic prophylaxis, and effect of severe infections on final outcome. Thirty-eight patients (19%) developed a severe infection early during induction therapy and most infections were pneumonia. Only one patient died due to septic shock during neutropenia. No significant differences were reported in terms of progression-free survival (PFS) and overall survival (OS) between patients developing a severe infection and those who did not. Multivariate analysis determined a monoclonal component >3 g/dL and platelets thalidomide combinations with high tumor burden are at high risk of developing severe infections and require primary antibiotic prophylaxis, whereas in other patients it is questionable. However, patient final outcome was not affected by infection development. PMID:21338282

  18. Fast and Simultaneous Analysis of Combined Anti-Diabetic Drugs by Capillary Zone Electrophoresis.

    Science.gov (United States)

    Doomkaew, Athiporn; Prapatpong, Pornpan; Buranphalin, Sawanya; Vander Heyden, Yvan; Suntornsuk, Leena

    2015-07-01

    A fast capillary zone electrophoretic method with photodiode array detection (CZE-PAD) was established and validated for assays of commonly prescribed anti-diabetic drugs [metformin (MET), glibenclamide (GBM) and gliclazide (GCZ)] in 13 samples including raw material, single and combined tablets. CZE optimization revealed baseline separation of the analytes (Rs > 5.39) in 8 min, in 50 mM borate buffer (pH 9.0), using a capillary with an effective length of 56.0 cm and an inner diameter of 50 µm, a voltage of 20 kV, a temperature of 25°C and a detection wavelength at 210 nm. The method provides excellent linearity, precision (%RSDs < 1.90%), recovery (99.8-101.0%) and low detection and quantitation limits (<4 and 12 µg/mL, respectively). The procedure was fast (seven samples per hour) and cost effective, since no organic solvent, sample pre-treatments or clean-up procedures were required. Importantly, the method was accurate, sensitive and reliable for routine quality control of MET, GBM and GCZ in pharmaceutical products both in single and combined formulations. PMID:25344839

  19. Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2013-07-01

    Full Text Available The objective of the study was to prepare solid dispersions containing a thermally unstable drug by hot-melt extrusion (HME. Carbamazepine (CBZ was selected as model drug and combinations of Kollidon VA64 (VA64, Soluplus (SOL and Eudragit EPO (EPO were utilized as carriers. Preformulation was conducted to identify the suitability of polymer combinations based on solubility parameters, differential scanning calorimetry (DSC, hot stage microscopy and thermogravimetric analysis. Physicochemical properties of solid dispersions were determined by DSC, X-ray diffraction, fourier transform infrared spectroscopy, dissolution and accelerated stability testing. The results show that drug-polymer miscibility at temperatures below the melting point (Tm of CBZ was improved by combining EPO with VA64 or SOL. With 30% drug loading in a solid dispersion in SOL:EPO (1:1, w/w, CBZ was mainly present in an amorphous form accompanied by a small amount of a microcrystalline form. The dissolution rate of the solid dispersion was significantly increased (approximately 90% within 5 min compared to either the pure drug (approximately 85% within 60 min or the corresponding physical mixture (approximately 80% within 60 min before and after storage. The solid dispersion in SOL:EPO (1:1, w/w was relatively stable at 40 °C/75% RH under CBZ tablet packaging conditions for at least 3 months. In conclusion, polymer combinations that improve drug-polymer miscibility at an HME processing temperature below the Tm of a drug appear to be beneficial in the preparation of solid dispersions containing thermally unstable drugs.

  20. Boceprevir in combination with HIV protease inhibitors in patients with advanced fibrosis-altered drug-drug interactions?

    OpenAIRE

    Schwarze-Zander, C; C Boesecke; L Dold; J Wasmuth; Rockstroh, J

    2012-01-01

    In HIV/HCV co-infected patients improved treatment outcomes have been reported for the HCV protease inhibitors (PIs) boceprevir (BOC) and telaprevir (TVR), reaching SVR rates of up to 70% in pilot trials. Due to complex drug-drug-interactions triple therapy is substantially limited in HIV/HCV-coinfected individuals. Co-administration of BOC with the commonly available HIV PIs has been reported not only to decrease the level of BOC but also to lead to relevant decreases in the respective HIV P...

  1. Triple combination of amantadine, ribavirin, and oseltamivir is highly active and synergistic against drug resistant influenza virus strains in vitro.

    Directory of Open Access Journals (Sweden)

    Jack T Nguyen

    Full Text Available The rapid emergence and subsequent spread of the novel 2009 Influenza A/H1N1 virus (2009 H1N1 has prompted the World Health Organization to declare the first pandemic of the 21st century, highlighting the threat of influenza to public health and healthcare systems. Widespread resistance to both classes of influenza antivirals (adamantanes and neuraminidase inhibitors occurs in both pandemic and seasonal viruses, rendering these drugs to be of marginal utility in the treatment modality. Worldwide, virtually all 2009 H1N1 and seasonal H3N2 strains are resistant to the adamantanes (rimantadine and amantadine, and the majority of seasonal H1N1 strains are resistant to oseltamivir, the most widely prescribed neuraminidase inhibitor (NAI. To address the need for more effective therapy, we evaluated the in vitro activity of a triple combination antiviral drug (TCAD regimen composed of drugs with different mechanisms of action against drug-resistant seasonal and 2009 H1N1 influenza viruses. Amantadine, ribavirin, and oseltamivir, alone and in combination, were tested against amantadine- and oseltamivir-resistant influenza A viruses using an in vitro infection model in MDCK cells. Our data show that the triple combination was highly synergistic against drug-resistant viruses, and the synergy of the triple combination was significantly greater than the synergy of any double combination tested (P<0.05, including the combination of two NAIs. Surprisingly, amantadine and oseltamivir contributed to the antiviral activity of the TCAD regimen against amantadine- and oseltamivir-resistant viruses, respectively, at concentrations where they had no activity as single agents, and at concentrations that were clinically achievable. Our data demonstrate that the TCAD regimen composed of amantadine, ribavirin, and oseltamivir is highly synergistic against resistant viruses, including 2009 H1N1. The TCAD regimen overcomes baseline drug resistance to both classes of

  2. Proteomic response of methicillin-resistant S. aureus to a synergistic antibacterial drug combination: a novel erythromycin derivative and oxacillin.

    Science.gov (United States)

    Liu, Xiaofen; Pai, Pei-Jin; Zhang, Weipeng; Hu, Yingwei; Dong, Xiaojing; Qian, Pei-yuan; Chen, Daijie; Lam, Henry

    2016-01-01

    The use of antibacterial drug combinations with synergistic effects is increasingly seen as a critical strategy to combat multi-drug resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). In this work, the proteome responses in MRSA under the stress of a sub-inhibitory dose of a synergistic drug combination of a novel erythromycin derivative, SIPI-8294, and oxacillin, were studied by label-free quantitative proteomics. Several control treatment groups were designed to isolate proteome responses potentially related to the synergy: (1) the non-synergistic drug combination of erythromycin and oxacillin, (2) SIPI-8294 only, (3) oxacillin only and (4) erythromycin only. Results showed that 200 proteins were differentially expressed in SIPI-8294/oxacillin-treated cells. Among these proteins, the level of penicillin binding protein 2a, the protein mainly responsible for oxacillin resistance in MRSA, was four times lower in the SIPI-8294/oxacillin group than in the erythromycin/oxacillin group, suggesting that SIPI-8294 may interfere with this known oxacillin resistance mechanism. Moreover, hierarchical clustering analysis of differentially expressed proteins under different treatments revealed that SIPI-8294/oxacillin elicits very different responses than the individual drugs or the non-synergistic erythromycin/oxacillin combination. Bioinformatic analysis indicated that the synergistic effect can be further traced to a disruption in oxidation-reduction homeostasis and cell wall biosynthesis. PMID:26806358

  3. 77 FR 22327 - Draft Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products...

    Science.gov (United States)

    2012-04-13

    ... concerns regarding the development of antimicrobial resistance in human and animal bacterial pathogens when... those products consistent with FDA's GFI 209, ``The Judicious Use of Medically Important Antimicrobial... of a final guidance entitled ``The Judicious Use of Medically Important Antimicrobial Drugs in...

  4. Reversal of the multidrug resistance by drug combination using multifunctional liposomes

    Science.gov (United States)

    Patel, Niravkumar R.

    One of the major obstacles to the success of cancer chemotherapy is the multi-drug resistance (MDR) that results due mainly to the over-expression of drug efflux transporter pumps such as P-glycoprotein (P-gp). Highly efficacious third generation P-gp inhibitors, like tariquidar, have shown promising results against MDR. However, P-gp is also expressed in normal tissues like the blood-brain barrier, gastrointestinal tract, liver and kidney. It is therefore important to limit the exposure of P-gp inhibitors to normal tissues and increase their co-localization with anticancer agents in tumor tissues to maximize the efficacy of a P-gp inhibitor. To minimize non-specific binding and increase its delivery to tumor tissues, liposomes, self-assembling phospholipid vesicles, were chosen as a drug delivery vehicle. The liposome has been identified as a system capable of carrying molecules with diverse physicochemical properties. It can also alter the pharmacokinetic profile of loaded molecules which is a concern with both tariquidar and paclitaxel. Liposomes can easily be surface-modified rendering them cell-specific as well as organelle-specific. The main objective of present study was to develop an efficient liposomal delivery system which would deliver therapeutic molecules of interest to tumor tissues and avoid interaction with normal tissues. In this study, the co-delivery of tariquidar and paclitaxel into tumor cells to reverse the MDR using long-circulating cationic liposomes was investigated. SKOV-3TR, the resistant variant of SKOV-3 and MCF-7/ADR, the resistant variant of MCF-7 were used as model cell lines. Uniform liposomal formulations were generated with high incorporation efficiency and no apparent decrease in tariquidar potency towards P-gp. Tariquidar- and paclitaxel- co-loaded long-circulating liposomes showed significant re-sensitization of SKOV-3TR and MCF-7/ADR for paclitaxel in vitro. Further modification of these liposomes with antitumor 2C5 resulted

  5. Practice of self-medication of mifepristone-misoprostol drug combination for medical abortion

    Directory of Open Access Journals (Sweden)

    Sushila Godara

    2014-06-01

    However, the use of mifepristone and ndash; misoprostol combination for medical abortion used as self-medication, is rising due to changing socio-cultural practices and increased awareness among women for the termination of early pregnancy up to 63 days. It is observed that many women indulge in the practice of self-medication for termination of pregnancy. They take medicines either from local pharmacists, nurses, on advice of relatives, friends, husband, neighbors, newspaper articles, radio, television, magazines or any other such unauthorized sources for termination of pregnancy which mostly leads to incomplete abortion or many complications. It is observed that only few number of women have complete abortion with self-medication from an unauthorized source and moreover they suffer from pain and heavy bleeding when compared to normal menstrual flow. It is noticed that now-a-days, these drugs are used irrationally and nonjudiciously. Women are thus advised to take proper regimen of mifepristone and misoprostol under the guidance of an authorized practitioner and if they still fail to abort, then they have to undergo surgical evacuation that is, vaccum aspiration for termination of pregnancy. [Int J Basic Clin Pharmacol 2014; 3(3.000: 572-573

  6. Intra-articular drug injections in the combination treatment of rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Yu. A. Olyunin

    2015-01-01

    Full Text Available In clinical practice, intra-articular injections of glucocorticoids (GC are widely used to treat chronic joint inflammatory diseases, osteoarthritis (OA, and extra-articular soft tissue involve-ment. GCs given to patients with chronic arthritis may rapidly suppress joint inflammatory changes and ensure significant clinical improvements well before there is a benefit of prescribed disease-modifying antirheumatic drugs. According to the clinical features of disease, GCs may be used for systemic or local treatment in each specific case and a combination of these two treatments may be performed in some patients. In OA patents, the effect of intra-articular GC injections is less sustained than in those with joint inflammatory diseases and it persists for an average of about 3 weeks. Intra-articular hyaluronic acid is likely to be a more promising treatment for OA. It may also relieve pain considerably and improve joint functions. At the same time the highest effect was noted between weeks 5 and 13 after injection, but improvement also persisted after 14–26 weeks or longer in a number of cases.

  7. Interaction between antitumor drug and silver nanoparticles:combined fluorscence and surface enhanced Raman scattering study

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Hong Wang; Zhuyuan Wang; Xuebin Tan; Chunyuan Song; Ruohu Zhang; Jin Li; Yiping Cui

    2009-01-01

    Optical methods and MTT method are used to characterize the antiproliferation effect of antitumor drug 9-aminoacridine (9AA) with and without silver nanoparticles.Intracellular surface enhanced Raman scat tering (SERS) spectra and fluorescent spectra of 9AA indicate the form of 9AA adsorbed on the surface of silver nanoparticles.Although both silver nanoparticles and antitumor drug can inhibit the growth of Hela cells,silver nanoparticles can slow down the antiproliferation effect on Hela cells at low concentration of antitumor drugs.Our experimental results suggest that silver nanoparticles may serve as slow-release drug carriers,which is important in antitumor drug delivery.

  8. Combination of PIM and JAK2 inhibitors synergistically suppresses cell proliferation and overcomes drug resistance of myeloproliferative neoplasms

    OpenAIRE

    Huang, Shih-Min A.; Wang, Anlai; Greco, Rita; LI, Mrs Zhifang; Sun, Fangxian; Barberis, Claude; Tabart, Michel; Patel, Vinod; Schio, Laurent; Hurley, Raelene; Chen, Bo; Cheng, Hong; Lengauer, Christoph; Pollard, Jack; Watters, James

    2014-01-01

    Inhibitors of JAK2 kinase are emerging as an important treatment modality for myeloproliferative neoplasms (MPN). However, similar to other kinase inhibitors, resistance to JAK2 inhibitors may eventually emerge through a variety of mechanisms. Effective drug combination is one way to enhance therapeutic efficacy and combat resistance against JAK2 inhibitors. To identify potential combination partners for JAK2 compounds in MPN cell lines, we performed pooled shRNA screen targeting 5,000 genes ...

  9. Preclinical drug evaluation for combination therapy in acute stroke using systematic review, meta-analysis, and subsequent experimental testing

    OpenAIRE

    O'Collins, Victoria E; Macleod, Malcolm R.; Cox, Susan F; van Raay, Leena; Aleksoska, Elena; Donnan, Geoffrey A.; Howells, David W.

    2010-01-01

    There is some evidence that in animal models of acute ischaemic stroke, combinations of neuroprotective agents might be more efficacious than the same agents administered alone. Hence, we developed pragmatic, empirical criteria based on therapeutic target, cost, availability, efficacy, administration, and safety to select drugs for testing in combination in animal models of acute stroke. Magnesium sulphate, melatonin, and minocycline were chosen from a library of neuroprotective agents, and w...

  10. COMPARISION OF TWO DRUG COMBINATIONS FOR LABOUR ANALGESIA, AND ITS EFFECT ON PATIENT SATISFACTION, DURATION OF LABOUR AND FETAL OUTCOME

    OpenAIRE

    Jaideep; Pallavi

    2014-01-01

    : BACKGROUND: Epidural is now established and accepted method to relief labour pain. This study intended to comparison of two drug combinations in labour analgesia and its effect on duration of labour, maternal satisfaction and fetal outcome. Combined epidural infusion of bupivacaine + fentanyl would result in analgesia superior to that provided by a continuous epidural infusion of a similar concentration of Bupivacaine alone. AIMS AND OBJECTIVE: To compare the efficacy of...

  11. Collateral Resistance and Sensitivity Modulate Evolution of High-Level Resistance to Drug Combination Treatment in Staphylococcus aureus

    DEFF Research Database (Denmark)

    de Evgrafov, Mari Cristina Rodriguez; Gumpert, Heidi; Munck, Christian;

    2015-01-01

    As drug-resistant pathogens continue to emerge, combination therapy will increasingly be relied upon to treat infections and to help combat further development of multidrug resistance. At present a dichotomy exists between clinical practice, which favors therapeutically synergistic combinations......, and the scientific model emerging from in vitro experimental work, which maintains that this interaction provides greater selective pressure toward resistance development than other interaction types. We sought to extend the current paradigm, based on work below or near minimum inhibitory...... concentration levels, to reflect drug concentrations more likely to be encountered during treatment. We performed a series of adaptive evolution experiments using Staphylococcus aureus. Interestingly, no relationship between drug interaction type and resistance evolution was found as resistance increased...

  12. Effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    黄大海

    2012-01-01

    Objective To investigate the effect of combined anti-platelets drugs on platelet activation in the elderly patients with acute coronary syndrome(ACS).Methods Totally 72 elderly patients with ACS were divided randomly into two groups according to age ≤80 years and>80 years.

  13. Treatment of Breast Cancer Cells by IGF1R Tyrosine Kinase Inhibitor Combined with Conventional Systemic Drugs

    NARCIS (Netherlands)

    Hartog, H.; Van der Graaf, W. T. A.; Boezen, H. M.; Wesseling, J.

    2012-01-01

    Aim: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase receptor mediating cell growth and survival of cancer cells. We studied responses to IGF1R tyrosine kinase inhibitor NVP-AEW541 combined with conventional systemic drugs in breast cancer cell lines of different clinical subtype.

  14. Treatment of breast cancer cells by IGF1R tyrosine kinase inhibitor combined with conventional systemic drugs.

    NARCIS (Netherlands)

    Hartog, H.; Graaf, W.T.A. van der; Boezen, H.M.; Wesseling, J.

    2012-01-01

    AIM: Insulin-like growth factor-1 receptor (IGF1R) is a tyrosine kinase receptor mediating cell growth and survival of cancer cells. We studied responses to IGF1R tyrosine kinase inhibitor NVP-AEW541 combined with conventional systemic drugs in breast cancer cell lines of different clinical subtype.

  15. In vitro synergy of colistin combinations against extensively drug-resistant Acinetobacter baumannii producing OXA-23 carbapenemase.

    Science.gov (United States)

    Wei, Wenjuan; Yang, Haifei; Liu, Yanyan; Ye, Ying; Li, Jiabin

    2016-06-01

    Fifty extensively drug-resistant Acinetobacter baumannii (XDRAB) were isolated from patients. The chequerboard microdilution method was used to determine the in vitro activities of five colistin (COL)-based combinations including COL+fosfomycin (FOS), COL+rifampicin (RIF), COL+imipenem (IMP), COL+sulbactam (SUP) and COL+levofloxacin (LVX). The synergistic activity was evaluated by the fractional inhibitory concentration index (FICI). According to our results, the combination of COL was synergistic with FOS, RIF, IMP, SUP and LVX with the ratios of 50, 72, 88, 92 and 64%, respectively. When combined with COL, the other five agents showed increased antimicrobial activities. In addition, two of the combinations, COL+RIF and COL+IMP, were more active than the combinations of COL+FOS, COL+SUP and COL+LVX. More importantly, these combination regimens could exert synergistic effects at the sub-minimum inhibitory concentration (MIC) levels against XDRAB strains. PMID:25978105

  16. Physiologically structured cell population dynamic models with applications to combined drug delivery optimisation in oncology

    OpenAIRE

    Clairambault, Jean; Fercoq, Olivier

    2016-01-01

    In this paper, we introduce a model for drug delivery optimisation in a chronotherapeu-tics framework. We present a pharmacokinetics and pharmacodynamics model for oxaliplatin and 5-Fluorouracil, a classic therapeutic association in the treatment of colorectal cancer. We derive the phar-macokinetics model using law of mass action and enzyme kinetics. We design an age-structured cell cycle PDE model with drug damage and repair phases to account for the effect of the drugs on proliferating cell...

  17. Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs

    OpenAIRE

    Jiang, Pengfei; Mukthavavam, Rajesh; Chao, Ying; Bharati, Ila Sri; Fogal, Valentina; Pastorino, Sandra; Cong, Xiuli; Nomura, Natsuko; Gallagher, Matt; Abbasi, Taher; Vali, Shireen; Pingle, Sandeep C; Makale, Milan; Kesari, Santosh

    2014-01-01

    Background Glioblastoma (GBM) is a therapeutic challenge, associated with high mortality. More effective GBM therapeutic options are urgently needed. Hence, we screened a large multi-class drug panel comprising the NIH clinical collection (NCC) that includes 446 FDA-approved drugs, with the goal of identifying new GBM therapeutics for rapid entry into clinical trials for GBM. Methods Screens using human GBM cell lines revealed 22 drugs with potent anti-GBM activity, including serotonergic blo...

  18. Combining Human Disease Genetics and Mouse Model Phenotypes towards Drug Repositioning for Parkinson’s disease

    OpenAIRE

    Chen, Yang; Cai, Xiaoshu; Xu, Rong

    2015-01-01

    Parkinson’s disease (PD) is a severe neurodegenerative disorder without effective treatments. Here, we present a novel drug repositioning approach to predict new drugs for PD leveraging both disease genetics and large amounts of mouse model phenotypes. First, we identified PD-specific mouse phenotypes using well-studied human disease genes. Then we searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with PD. We demonstrated the validity of our approach u...

  19. Drug-eluting stents and acute myocardial infarction:A lethal combination or friends?

    Institute of Scientific and Technical Information of China (English)

    Shuji; Otsuki; Manel; Sabaté

    2014-01-01

    Primary percutaneous coronary intervention is the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction(STEMI). First generation drug-eluting stents(DES),(sirolimus drug-eluting stents and paclitaxel drug-eluting stents), reduce the risk of restenosis and target vessel revascularization compared to bare metal stents. However, stent thrombosis emerged as a major safety concern with first generation DES. In response to these safety issues, second generation DES were developed with different drugs, improved stent platforms and more biocompatible durable or bioabsorbable polymeric coating. This article presents an overview of safety and efficacy of the first and second generation DES in STEMI.

  20. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice.

    OpenAIRE

    Horwitz, Joshua A.; Halper-Stromberg, Ariel; Mouquet, Hugo; Gitlin, Alexander D.; Tretiakova, Anna; Eisenreich, Thomas R.; Malbec, Marine; Gravemann, Sophia; Billerbeck, Eva; Dorner, Marcus; Büning, Hildegard; Schwartz, Olivier; Knops, Elena; Kaiser, Rolf; Seaman, Michael S

    2013-01-01

    Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, ...

  1. Individualization of treatments with drugs metabolized by CES1: combining genetics and metabolomics

    DEFF Research Database (Denmark)

    Rasmussen, Henrik B.; Bjerre, Ditte; Linnet, Kristian;

    2015-01-01

    CES1 is involved in the hydrolysis of ester group-containing xenobiotic and endobiotic compounds including several essential and commonly used drugs. The individual variation in the efficacy and tolerability of many drugs metabolized by CES1 is considerable. Hence, there is a large interest in in...

  2. Activities of colistin- and minocycline-based combinations against extensive drug resistant Acinetobacter baumannii isolates from intensive care unit patients

    Directory of Open Access Journals (Sweden)

    Li Jian

    2011-04-01

    Full Text Available Abstract Background Extensive drug resistance of Acinetobacter baumannii is a serious problem in the clinical setting. It is therefore important to find active antibiotic combinations that could be effective in the treatment of infections caused by this problematic 'superbug'. In this study, we analyzed the in vitro activities of three colistin-based combinations and a minocycline-based combination against clinically isolated extensive drug resistant Acinetobacter baumannii (XDR-AB strains. Methods Fourteen XDR-AB clinical isolates were collected. The clonotypes were determined by polymerase chain reaction-based fingerprinting. Susceptibility testing was carried out according to the standards of the Clinical and Laboratory Standards Institute. Activities of drug combinations were investigated against four selected strains and analyzed by mean survival time over 12 hours (MST12 h in a time-kill study. Results The time-kill studies indicated that the minimum inhibitory concentration (MIC of colistin (0.5 or 0.25 μg/mL completely killed all strains at 2 to 4 hours, but 0.5×MIC colistin showed no bactericidal activity. Meropenem (8 μg/mL, minocycline (1 μg/mL or rifampicin (0.06 μg/mL did not show bactericidal activity. However, combinations of colistin at 0.5×MIC (0.25 or 0.125 μg/mL with each of the above were synergistic and shown bactericidal activities against all test isolates. A combination of meropenem (16 μg/mL with minocycline (0.5×MIC, 4 or 2 μg/mL was synergitic to all test isolates, but neither showed bactericidal activity alone. The MST12 h values of drug combinations (either colistin- or minocycline-based combinations were significantly shorter than those of the single drugs (p Conclusions This study indicates that combinations of colistin/meropenem, colistin/rifampicin, colistin/minocycline and minocycline/meropenem are synergistic in vitro against XDR-AB strains.

  3. Impact and mechanism of non-steroidal anti-inflammatory drugs combined with chemotherapeutic drugs on human lung cancer-nude mouse transplanted tumors

    Science.gov (United States)

    SUN, WEIYI; CHEN, GANG

    2016-01-01

    The present study aimed to investigate the impact of indomethacin treatment combined with oxaliplatin treatment on the expression of cluster of differentiation 44 variant 6 (CD44v6), matrix metalloproteinase-2 (MMP-2) and survivin in human lung cancer-nude mouse transplanted tumors. The human lung adenocarcinoma (A549)-nude mouse transplanted tumor model was established, and the mice were divided into a control group, an indomethacin treatment group, an oxaliplatin treatment group and an indomethacin-oxaliplatin combination treatment group. The tumor inhibition rate was calculated following sacrificing of the mice. Immunohistochemical staining and fluorescence reverse transcription-quantitative polymerase chain reaction were utilized to detect the protein and messenger (m)RNA expression of CD44v6, MMP-2 and survivin. The tumor inhibition rates of the indomethacin group, the oxaliplatin group and the combination group were 26.67, 47.70 and 68.88%, respectively. The protein and mRNA expression levels of CD44v6, MMP-2 and survivin in the transplanted tumors of each treatment group were reduced compared with the control group (Plung cancer-nude mouse transplanted tumors and the expression of CD44v6, MMP-2 and survivin inside the tumor. The combination of non-steroidal anti-inflammatory drugs with chemotherapeutic drugs may improve the antitumor effects.

  4. Will "Combined Prevention" Eliminate Racial/Ethnic Disparities in HIV Infection among Persons Who Inject Drugs in New York City?

    Directory of Open Access Journals (Sweden)

    Don Des Jarlais

    Full Text Available It has not been determined whether implementation of combined prevention programming for persons who inject drugs reduce racial/ethnic disparities in HIV infection. We examine racial/ethnic disparities in New York City among persons who inject drugs after implementation of the New York City Condom Social Marketing Program in 2007. Quantitative interviews and HIV testing were conducted among persons who inject drugs entering Mount Sinai Beth Israel drug treatment (2007-2014. 703 persons who inject drugs who began injecting after implementation of large-scale syringe exchange were included in the analyses. Factors independently associated with being HIV seropositive were identified and a published model was used to estimate HIV infections due to sexual transmission. Overall HIV prevalence was 4%; Whites 1%, African-Americans 17%, and Hispanics 4%. Adjusted odds ratios were 21.0 (95% CI 5.7, 77.5 for African-Americans to Whites and 4.5 (95% CI 1.3, 16.3 for Hispanics to Whites. There was an overall significant trend towards reduced HIV prevalence over time (adjusted odd ratio = 0.7 per year, 95% confidence interval (0.6-0.8. An estimated 75% or more of the HIV infections were due to sexual transmission. Racial/ethnic disparities among persons who inject drugs were not significantly different from previous disparities. Reducing these persistent disparities may require new interventions (treatment as prevention, pre-exposure prophylaxis for all racial/ethnic groups.

  5. New modules and assembled systems for the controlled release of drugs in combination

    OpenAIRE

    Benetti, Camillo

    2015-01-01

    Abstract Dome matrix technology is a module assembly technology for construction of delivery systems for time and space controlled release of drugs[1]. The objective of this work was the development via the use of Dome matrix technology of a floating dosage forms, useful for drugs administration with a very narrow absorption window or not soluble at intestinal pH, or the manufacture of a multi-drugs and multi-kinetics dosage form[2-4]. The first part of this thesis will focus on ...

  6. Chemotherapy combined with target drugs in the treatment of advanced colorectal cancer: A meta-analysis based on Chinese patients

    Directory of Open Access Journals (Sweden)

    Q H Zheng

    2014-01-01

    Full Text Available Background: Colorectal carcinoma is one of most diagnosed solid malignant carcinoma. The chemotherapy combined with target drugs in the treatment of advanced colorectal cancer in not conclusive. Methods: The clinical studies reporting the activity and adverse events between chemotherapy alone versus chemotherapy combined with anti-epidermal growth factor receptor drugs were screened in the databases of Medline, the Cochrane Library, Wanfang and CNKI and included in this meta-analysis. The risk ratio (RR and its 95% confidence interval (CI for treatment response and adverse events were pooled by random or fixed effect model. Results: A total of 10 clinical studies reporting chemotherapy combined with the target in the treatment of advanced colorectal cancer were included in this study. The pooled RR was 3.26 (95% CI: 1.74-6.11, P 0.05, liver function damage (RR = 1.03, 95% CI: 0.74-1.42, myelosuppression (RR = 1.04, 95% CI: 0.83-1.31 and neurotoxicity (RR = 1.12, 95% CI: 0.93-1.35 were not different between the two groups. Conclusion: For Chinese patients with advanced colorectal cancer, chemotherapy combined with target drug can improve the response rate, but also increase the risk of nausea and vomiting.

  7. Thermal, cardiorespiratory and cortisol responses of impala (Aepyceros melampus to chemical immobilisation with 4 different drug combinations

    Directory of Open Access Journals (Sweden)

    L.C.R. Meyer

    2008-05-01

    Full Text Available Thermometric data loggers were surgically implanted in 15 impala (Aepyceros melampus to investigate the consequences of chemical capture. Impala were darted and chemically immobilised for 30 min with each of the following drug combinations: etorphine and azaperone; etorphine and medetomidine; thiafentanil and azaperone, and a thiafentanil medetomidine combination. During immobilisation, pulse oximeter readings, respiratory rhythm, the plane of immobilisation and plasma cortisol concentrations were measured and recorded. The impala developed an extremely high rise in body temperature, which peaked 20-30 min after reversal of the immobilisation. The magnitude of the rise in body temperature was similar for all the drug combinations (F=0.8, P=0.5, but the duration of the hyperthermia was shorter when the thiafentanil and azaperone combination was used(F=3.35, P<0.05. Changes in body temperature were related to the time that it took for ananimal to become recumbent after darting (r2 = 0.45, P = 0.006 and not to the effect of the drug combination on time to recumbency (r2 = 0.29, P = 0.46. The relationship between time to recumbency and body temperature change, and also to plasma cortisol concentration(r2=0.67,P=0.008, indicated that physiological consequences of capture were related to the duration of exposure to a stress or, and not to the pharmacology of the capture drugs. Although shorter time to recumbency in individuals resulted in the benefit of smaller stress responses and body temperature changes, those individuals were predisposed to developing hypoxia and possibly induction apnoea. When animals are chemically immobilised,reducing the thermal consequences of capture requires limiting the exposure of the animal to a psychological 'fright stress'.

  8. Biodiversity conservation and drug discovery: Can they be combined? The Suriname and Madagascar experiences.

    Science.gov (United States)

    Cao, Shugeng; Kingston, David G I

    2009-08-01

    The approach to new drugs through natural products has proved to be the single most successful strategy for the discovery of new drugs, but in recent years its use has been deemphasized by many pharmaceutical companies in favor of approaches based on combinatorial chemistry and genomics, among others.Drug discovery from natural sources requires continued access to plant, marine, and microbial biomass, and so the preservation of tropical rainforests is an important part of our drug discovery program. Sadly, many of the tropical forests of the world are under severe environmental pressure, and deforestation is a serious problem in most tropical countries. One way to combat this loss is to demonstrate their value as potential sources of new pharmaceutical or agrochemical products.As part of an effort to integrate biodiversity conservation and drug discovery with economic development, we initiated an International Cooperative biodiversity Group (ICBG) to discover potential pharmaceuticals from the plant biodiversity of Suriname and Madagascar. The Group, established with funding from agencies of the United States government, involved participants from the USA, Suriname, and Madagascar. The basic approach was to search for bioactive plants in the Suriname and Malagasy flora, and to isolate their bioactive constituents by the best available methods, but the work included capacity building as well as research. Progress on this project will be reported, drawing on results obtained from the isolation of bioactive natural products from Suriname and Madagascar. The benefits of this general approach to biodiversity and drug discovery will also be discussed. PMID:20161050

  9. Successful treatment of methicillin-resistant Staphylococcus aureus osteomyelitis with combination therapy using linezolid and rifampicin under therapeutic drug monitoring.

    Science.gov (United States)

    Ashizawa, Nobuyuki; Tsuji, Yasuhiro; Kawago, Koyomi; Higashi, Yoshitsugu; Tashiro, Masato; Nogami, Makiko; Gejo, Ryuichi; Narukawa, Munetoshi; Kimura, Tomoatsu; Yamamoto, Yoshihiro

    2016-05-01

    Linezolid is an effective antibiotic against most gram-positive bacteria including drug-resistant strains such as methicillin-resistant Staphylococcus aureus. Although linezolid therapy is known to result in thrombocytopenia, dosage adjustment or therapeutic drug monitoring of linezolid is not generally necessary. In this report, however, we describe the case of a 79-year-old woman with recurrent methicillin-resistant S. aureus osteomyelitis that was successfully treated via surgery and combination therapy using linezolid and rifampicin under therapeutic drug monitoring for maintaining an appropriate serum linezolid concentration. The patient underwent surgery for the removal of the artificial left knee joint and placement of vancomycin-impregnated bone cement beads against methicillin-resistant S. aureus after total left knee implant arthroplasty for osteoarthritis. We also initiated linezolid administration at a conventional dose of 600 mg/h at 12-h intervals, but reduced it to 300 mg/h at 12-h intervals on day 9 because of a decrease in platelet count and an increase in serum linezolid trough concentration. However, when the infection exacerbated, we again increased the linezolid dose to 600 mg/h at 12-h intervals and performed combination therapy with rifampicin, considering their synergistic effects and the control of serum linezolid trough concentration via drug interaction. Methicillin-resistant S. aureus infection improved without reducing the dose of or discontinuing linezolid. The findings in the present case suggest that therapeutic drug monitoring could be useful for ensuring the therapeutic efficacy and safety of combination therapy even in patients with osteomyelitis who require long-term antibiotic administration. PMID:26732509

  10. Combination of Polymer Technology and Carbon Nanotube Array for the Development of an Effective Drug Delivery System at Cellular Level

    Directory of Open Access Journals (Sweden)

    Riggio Cristina

    2009-01-01

    Full Text Available Abstract In this article, a carbon nanotube (CNT array-based system combined with a polymer thin film is proposed as an effective drug release device directly at cellular level. The polymeric film embedded in the CNT array is described and characterized in terms of release kinetics, while in vitro assays on PC12 cell line have been performed in order to assess the efficiency and functionality of the entrapped agent (neural growth factor, NGF. PC12 cell differentiation, following incubation on the CNT array embedding the alginate delivery film, demonstrated the effectiveness of the proposed solution. The achieved results indicate that polymeric technology could be efficiently embedded in CNT array acting as drug delivery system at cellular level. The implication of this study opens several perspectives in particular in the field of neurointerfaces, combining several functions into a single platform.

  11. Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis.

    Science.gov (United States)

    Monzote, Lianet; Montalvo, Ana Margarita; Scull, Ramón; Miranda, Migdalia; Abreu, Juan

    2007-01-01

    To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil. PMID:17823757

  12. Performance of Combination Drug and Hygroscopic Excipient Submicrometer Particles from a Softmist Inhaler in a Characteristic Model of the Airways

    OpenAIRE

    Longest, P. Worth; Tian, Geng; Li, Xiang; Son, Yoen-Ju; Hindle, Michael

    2012-01-01

    Excipient enhanced growth (EEG) of inhaled submicrometer pharmaceutical aerosols is a recently proposed method intended to significantly reduce extrathoracic deposition and improve lung delivery. The objective of this study was to evaluate the size increase of combination drug and hygroscopic excipient particles in a characteristic model of the airways during inhalation using both in vitro experiments and CFD simulations. The airway model included a characteristic mouth-throat (MT) and upper ...

  13. Cannabinoid receptor-mediated antinociception with acetaminophen drug combinations in rats with neuropathic spinal cord injury pain

    OpenAIRE

    Hama, Aldric T; Sagen, Jacqueline

    2009-01-01

    Pre-clinical evidence demonstrates that neuropathic spinal cord injury (SCI) pain is maintained by a number of neurobiological mechanisms, suggesting that treatments directed at several pain-related targets may be more advantageous compared to a treatment focused on a single target. The current study evaluated the efficacy of the non-opiate analgesic acetaminophen, which has several putative analgesic mechanisms, combined with analgesic drugs used to treat neuropathic pain in a rat model of b...

  14. Colistin combination therapy improves microbiologic cure in critically ill patients with multi-drug resistant gram-negative pneumonia.

    Science.gov (United States)

    Parchem, N L; Bauer, K A; Cook, C H; Mangino, J E; Jones, C D; Porter, K; Murphy, C V

    2016-09-01

    Currently, in vitro synergy with colistin has not translated into improved clinical outcomes. This study aimed to compare colistin combination therapy to colistin monotherapy in critically ill patients with multi-drug resistant gram-negative (MDR-GN) pneumonia. This was a retrospective analysis of critically ill adult patients receiving intravenous colistin for MDR-GN pneumonia comparing colistin combination therapy to colistin monotherapy with a primary endpoint of clinical cure. Combination therapy was defined by administration of another antibiotic to which the MDR-GN pathogen was reported as susceptible or intermediate. Ninety patients were included for evaluation (41 combination therapy and 49 monotherapy). Baseline characteristics were similar between groups. No difference in clinical cure was observed between combination therapy and monotherapy in univariate analysis, nor when adjusted for APACHE II score and time to appropriate antibiotic therapy (57.1 vs. 63.4 %, adjusted OR 1.15, p = 0.78). Microbiological cure was significantly higher for combination therapy (87 vs. 35.5 %, p Colistin combination therapy was associated with a significant improvement in microbiological cure, without improvement in clinical cure. Based on the in vitro synergy and improvement in microbiological clearance, colistin combination therapy should be prescribed for MDR-GN pneumonia. Further research is warranted to determine if in vitro synergy with colistin translates into improved clinical outcomes. PMID:27230510

  15. Combining inkjet printing and amorphous nanonization to prepare personalized dosage forms of poorly-soluble drugs.

    Science.gov (United States)

    Cheow, Wean Sin; Kiew, Tie Yi; Hadinoto, Kunn

    2015-10-01

    Inkjet printing of drug nanosuspension on edible porous substrates was carried out for the first time with the objective of preparing personalized dosage forms of poorly soluble drugs. Amorphous drug-polysaccharide nanoparticle complex (or drug nanoplex in short) was used as the nanosuspension ink, instead of the conventional crystalline nanodrug. The amorphous drug nanoplex exhibited low propensity to Ostwald ripening growth, high colloidal stability, and supersaturation generation capability making it ideal for printing. Nanoplexes of ciprofloxacin - a BCS Class IV compound - prepared by complexation with dextran sulfate were used as the nanosuspension ink at two different sizes (i.e. ≈265nm and 188nm). Inkjet printing was performed on cellulose substrate at 0.25% (w/v) nanosuspension concentration and 5% (w/v) polyethylene glycol. For both nanoplex sizes, the results indicated that the printed dose could be increased by increasing the number of droplets dispensed. However, exact correlations between the achievable dose and the number of droplets dispensed were not evident, which was likely caused by the spatial non-homogeneity in the nanosuspension concentration. Compared to the larger nanoplex, printed nanodrugs of the smaller nanoplex consistently exhibited higher payload with better batch-to-batch reproducibility (nanodrug were successfully established in vitro. PMID:26325060

  16. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    Directory of Open Access Journals (Sweden)

    Barbara Szymanska

    Full Text Available Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL, or for re-induction post relapse, use a combination of vincristine (VCR, a glucocorticoid, and L-asparaginase (ASP with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX and ASP (VXL against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  17. A survey of the syntheses of active pharmaceutical ingredients for antiretroviral drug combinations critical to access in emerging nations.

    Science.gov (United States)

    Pinheiro, Eloan Dos Santos; Antunes, Octavio Augusto Ceva; Fortunak, Joseph M D

    2008-09-01

    It has been roughly 25 years since the threat posed by human immunodeficiency virus type 1 (HIV-1) became widely known. The cumulative death toll from HIV/AIDS is now greater than 25 million. There are approximately 33 million people living worldwide with this disease, of whom about 68% (22.5 million) live in sub-Saharan Africa (http://www.avert.org/worldstats.htm). A number of antiretroviral (ARV) drugs have been approved for treatment of HIV/AIDS. Inhibitors of HIV reverse transcriptase (RTIs) include the nucleoside/nucleotide drugs zidovudine, lamivudine, abacavir, didanosine, stavudine, emtricitabine and tenofovir disoproxil fumarate. Non-nucleoside RTIs include nevirapine, efavirenz and etravirine. Inhibitors of HIV protease (PIs) include saquinavir, ritonavir, lopinavir, nelfinavir, indinavir, fosamprenavir and atazanavir. Enfuvirtide inhibits the HIV fusion protein. The CCR5 chemokine antagonist maraviroc and the integrase inhibitor raltegravir were very recently approved by the US FDA. Fixed-dose combinations (FDCs) have been formulated to increase tolerability, convenience and compliance. First-line drug combinations are offered to treatment-naive patients, while second-line drugs are reserved for those who no longer respond adequately to first-line therapy. In developing countries a modest but increasing fraction of those infected have access to ARVs. The Clinton HIV/AIDS Initiative estimates that 2.4 million of the nearly 8 million individuals needing treatment in developing nations have access to some drugs. First-line FDCs used in resource-poor settings are largely combinations of two nucleoside RTIs and a non-nucleoside RTI or PI. The effectiveness of these combinations decreases over time, requiring a switch to combinations that retain potency in the presence of viral resistance. Increasing access to second-line FDCs and new developments in first-line ARV therapy are cost challenges. In high-income countries the cost of ARV therapy is largely

  18. Combination of click chemistry and controlled radical polymerization for synthesis of advanced polymer drug delivery systems

    Czech Academy of Sciences Publication Activity Database

    Pechar, Michal; Pola, Robert; Braunová, Alena; Laga, Richard; Ulbrich, Karel

    2013-01-01

    Roč. 9, č. 1 (2013), s. 106-107 /3P10/. ISSN 1336-7242. [Zjazd chemikov /65./. 09.09.2013-13.09.2013, Tatranské Matliare] R&D Projects: GA ČR GCP207/12/J030 Institutional support: RVO:61389013 Keywords : polymer conjugates * controlled drug delivery * diagnostics of tumors Subject RIV: CD - Macromolecular Chemistry

  19. Recycling antibiotics into GUMBOS: A new combination strategy to combat multi-drug resistant bacteria

    Science.gov (United States)

    The emergence of multi-drug resistant bacteria, coupled with the lack of new antibiotics in development, is fast evolving into a global crisis. New strategies utilizing existing antibacterial agents are urgently needed. We propose one such strategy in which four outmoded ß-lactam antibiotics (amp...

  20. Drugs used in pediatric intravenous therapy: a study on potentialy interactive combination

    Directory of Open Access Journals (Sweden)

    Tathiana Silva de Souza Martins

    2012-04-01

    Full Text Available The aim of this study was: to identify and classify the main drugs administered by intravenous method in the prescriptions of the pediatric units and to verify the occurrence of potentially medicamentous interactions. It is an exploratory descriptive research, with quantitative treatment of the data. The population was formed by 1,248 pediatric prescriptions and the sample of 205, having as inclusion criteria prescriptions with intravenous therapy of two or more drugs. Data collection was made at the Medical Files of a University Hospital. It was verified that most of the drugs used presented interactive potential; 60% of the sample had been exposed to the co-administration of antimicrobials. The vancomycin was the most present agent, and all the children used an antimicrobial during the institutionalization period. It was concluded that the co-administration of potentially interactive drugs associated to simultaneous scheduling of administration of such agents could predispose the patients to undesired events, affecting, this way, the safety of the therapy.

  1. Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

    International Nuclear Information System (INIS)

    Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosis rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.

  2. BRAID: A Unifying Paradigm for the Analysis of Combined Drug Action.

    Science.gov (United States)

    Twarog, Nathaniel R; Stewart, Elizabeth; Hammill, Courtney Vowell; A Shelat, Anang

    2016-01-01

    With combination therapies becoming increasingly vital to understanding and combatting disease, a reliable method for analyzing combined dose response is essential. The importance of combination studies both in basic and translational research necessitates a method that can be applied to a wide range of experimental and analytical conditions. However, despite increasing demand, no such unified method has materialized. Here we introduce the Bivariate Response to Additive Interacting Doses (BRAID) model, a response surface model that combines the simplicity and intuitiveness needed for basic interaction classifications with the versatility and depth needed to analyze a combined response in the context of pharmacological and toxicological constraints. We evaluate the model in a series of simulated combination experiments, a public combination dataset, and several experiments on Ewing's Sarcoma. The resulting interaction classifications are more consistent than those produced by traditional index methods, and show a strong relationship between compound mechanisms and nature of interaction. Furthermore, analysis of fitted response surfaces in the context of pharmacological constraints yields a more concrete prediction of combination efficacy that better agrees with in vivo evaluations. PMID:27160857

  3. Evaluation of activity and combination strategies with the microtubule-targeting drug sagopilone in breast cancer cell lines

    Directory of Open Access Journals (Sweden)

    Julia eEschenbrenner

    2011-11-01

    Full Text Available The molecular heterogeneity of cancer calls for individualized therapies to become the standard of care. The development of new therapeutic agents needs to include integrative translational research as early as possible. Target-specific compounds require specific diagnostic biomarker support. Tailored treatment approaches, such as specific schedules or combinations, can improve the therapeutic outcome of drugs with more general mode of action, i.e. the classical chemotherapy. Results from translational research will allow to define the optimal patient population, to tailor individual treatment and to choose treatment combinations on a rational basis.Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent optimized for high in vitro and in vivo activity against a broad range of tumor models, including those resistant to paclitaxel and other systemic treatments. Sagopilone development was accompanied by translational research studies to evaluate the molecular mode of action, to recognize mechanisms leading to resistance, to identify predictive response biomarkers and to establish a rationale for combination with different therapies.Here, we present an RNAi drug modifier screen interrogating 300 genes in four cancer cell lines. Defects of the spindle assembly checkpoint (SAC were identified to cause resistance against sagopilone-induced mitotic arrest and apoptosis. Potential biomarkers for resistance are SAC-defects like mutations in the SAC-kinase BUB1B and chromosomal heterogeneity and polyploidy since they imply an increased tolerance for aberrant mitosis. The RNAi drug modifier screen identified the enhancement of sagopilone-induced mitotic arrest by inhibition of the mitotic kinesin KIF2C (MCAK as potential combination strategy.These new findings are correlated with results from previous studies. We discuss successes and failures of our integrative preclinical development program and provide recommendations for future

  4. In Vivo Efficacy of Drugs against Toxoplasma gondii Combined with Immunomodulators.

    Science.gov (United States)

    Köksal, Zeynep Şentürk; Yanik, Keramettin; Bilgin, Kemal; Yılmaz, Esmeray Mutlu; Hokelek, Murat

    2016-03-23

    The aim of this study is to evaluate the effects of pyrimethamine (PYR) and sulfadiazine (SDZ) combined with levamisole and echinacea on the survival of mice infected with Toxoplasma gondii. For this, we used 99 specific pathogen-free BALB/c mice. All the mice were infected intraperitoneally with 10(5) T. gondii tachyzoites and were divided into 11 groups, each including 9 mice. Except for the control group, oral treatment was initiated in all groups 24 h post infection and was continued for 10 days. The treatment regimen included dual combinations of PYR (dose, 6.25 and 12.5 mg/kg/day) and SDZ (dose, 100 and 200 mg/kg/day), triple combinations of PYR + SDZ, and levamisole (dose, 2.5 mg/kg/day) or echinacea (dose, 130 and 260 mg/kg/day) and echinacea alone (dose, 130 and 260 mg/kg/day). We observed that an effective dose of the combination of PYR + SDZ and levamisole resulted in a statistically significant increase in the survival rate from 33.3% to 88.9%. Similarly, half the dose of this combination resulted an increase in the survival rate from 0% to 44.4% (p < 0.05). Survival rate also increased in the groups treated with the combinations including echinacea; however, the difference did not reach statistical significance. The triple combination of PYR-SDZ-levamisole could be an alternative treatment option in case of infections caused by T. gondii. PMID:26166498

  5. Rational use of nonsteroidal anti-inflammatory drugs and proton pump inhibitors in combination for rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Wolfgang W Bolten

    2010-09-01

    Full Text Available Wolfgang W BoltenDivision of Rheumatology, Klaus-Miehlke Klinik, Wiesbaden, GermanyAbstract: Nonsteroidal anti-inflammatory drugs (NSAIDs are successfully used to alleviate pain and inflammation in rheumatic diseases. In an appreciable percentage of cases, the use of systemic NSAIDs is associated with adverse lesions of the gastrointestinal (GI mucosa up to life-threatening perforations, ulcers, and bleeding. Reliable warning signals mostly do not arise. Therefore, it is important to take preventive measures to reduce the GI risk. One established method is to assign cyclooxygenase 2 (COX-2-specific inhibitors (coxibs instead of traditional NSAIDs (tNSAIDs. Coxibs spare in part the endogenous gastroprotective mechanisms. Another reliable choice to improve the GI safety is the comedication of proton pump inhibitors (PPIs to suppress gastric acid. A fixed NSAID/PPI combination ensures expected protective effects by improving patients’ PPI adherence and physicians’ PPI prescription persistence. A fixed combination of enteric-coated naproxen and immediate-release esomeprazole has just been approved by the US Food and Drug Administration. PPI combinations with aspirin, other tNSAIDs, and coxibs are desirable. Patients in all risk groups, even patients at low risk of GI adverse events, benefit from concomitant protective measures. Moreover, the literature suggests that NSAID/PPI combinations are cost effective, including for patients in low-GI-risk groups. Pricing of fixed NSAID/PPI combinations will play a pivotal role for their broad acceptance in the future.Keywords: PPI, NSAID, fixed combination, gastrointestinal, adverse events, prevention

  6. Treatment of malignant digestive tract obstruction by combined intraluminal stent installation and intra-arterial drug infusion

    Institute of Scientific and Technical Information of China (English)

    Ai-Wu Mao; Zhong-Du Gao; Jia-Yu Xu; Ren-Jie Yancg; Xiang-Seng Xiao; Ting-Hui Jiang; Wei-Jun Jiang

    2001-01-01

    AIM To study the palliative treatment of malignant obstrution of digestive tract with placement of intraluminal stent combined with intra-arterial infusion of chemotherapeutic drugs. METHODS A total of 281 cases of digestive tract malignant obstruction were given per oral (esophagus,stomach, duodenum and jejunum), per anal (colon and rectum ) and percutaneous transhepatic ( biliary )installation of metallic stent. Among them, 205 cases received drug infusion by cannulation of tumor supplying artery with Seldingers technique. RESULTS Altogether 350 stents were installed in 281 cases, obstructive symptoms were relieved or ameliorated after installation. Occurrence of restenotic obstruction was 8 - 43 weeks among those with intraarterial drug infusion, which was later than 4 - 26 weeks in the group with only stent installation. The average survival time of the former group was 43 (3 - 105) weeks,which was significantly longer than 15 (3- 24) weeks of the latter group. CONCLUSION Intraluminal placement of stent combined with intra-arterial infusion chemotherapy is one of the effective palliative therapies for malignant obstruction of the digestive tract with symptomatic as well as etiological treatment.

  7. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    OpenAIRE

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2013-01-01

    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abno...

  8. Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

    OpenAIRE

    Wang ZY; Chen M; Zhu LL; Yu LS; Zeng S.; Xiang MX; Zhou Q

    2015-01-01

    Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing...

  9. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    Directory of Open Access Journals (Sweden)

    Mohite P.B.

    2012-06-01

    Full Text Available Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed.

  10. Combined Phosphoproteomics and Bioinformatics Strategy in Deciphering Drug Resistant Related Pathways in Triple Negative Breast Cancer

    Directory of Open Access Journals (Sweden)

    Xinyu Deng

    2014-01-01

    Full Text Available Because of the absence of a clear therapeutic target for triple negative breast cancer (TNBC, conventional chemotherapy is the only available systemic treatment option for these patients. Despite chemotherapy treatment, TNBC patients still have worse prognosis when compared with other breast cancer patients. The study is to investigate unique phosphorylated proteins expressed in chemoresistant TNBC cell lines. In the current study, twelve TNBC cell lines were subjected to drug sensitivity assays against chemotherapy drugs docetaxel, doxorubicin, gemcitabine, and cisplatin. Based on their half maximal inhibitory concentrations, four resistant and two sensitive cell lines were selected for further analysis. The phosphopeptides from these cells were enriched with TiO2 beads and fractionated using strong cation exchange. 1,645 phosphoprotein groups and 9,585 unique phosphopeptides were identified by a high throughput LC-MS/MS system LTQ-Orbitrap. The phosphopeptides were further filtered with Ascore system and 1,340 phosphoprotein groups, 2,760 unique phosphopeptides, and 4,549 unique phosphosites were identified. Our study suggested that differentially phosphorylated Cdk5, PML, AP-1, and HSF-1 might work together to promote vimentin induced epithelial to mesenchymal transition (EMT in the drug resistant cells. EGFR and HGF were also shown to be involved in this process.

  11. COMPARISION OF TWO DRUG COMBINATIONS FOR LABOUR ANALGESIA, AND ITS EFFECT ON PATIENT SATISFACTION, DURATION OF LABOUR AND FETAL OUTCOME

    Directory of Open Access Journals (Sweden)

    Jaideep

    2014-09-01

    Full Text Available : BACKGROUND: Epidural is now established and accepted method to relief labour pain. This study intended to comparison of two drug combinations in labour analgesia and its effect on duration of labour, maternal satisfaction and fetal outcome. Combined epidural infusion of bupivacaine + fentanyl would result in analgesia superior to that provided by a continuous epidural infusion of a similar concentration of Bupivacaine alone. AIMS AND OBJECTIVE: To compare the efficacy of two drug combinations for labour analgesia, and its effect on patient satisfaction, duration of labour and fetal outcome. MATERIALS AND METHODS: Study design – comparative randomized controlled study. Sample size: For this study 50 pregnant women were randomly selected and divided into two groups. GROUP I: Control Group (Continuous epidural infusion of Bupivacaine CEI: 25 parturient who were given a bolus of 0.1% Bupivacaine + 20mcg Fentanyl followed by infusion of 0.0625% Bupivacaine epidurally. GROUP II: Study Group (Continuous epidural infusion of Bupivacaine with Fentanyl CEIF: 25 parturients who were given a bolus of 0.1% Bupivacaine + 20mcg Fentanyl followed by infusion of 0.0625% Bupivacaine + 0.0001% Fentanyl epidurally. Duration of labour, Analgesia, maternal satisfaction, fetal outcome was assessed by different scales like bromage scale, visual analogue scale, APGAR score and pin prick method are used. Side effects and complications, if present were recorded.

  12. Blinded Evaluation of Combination Drug Therapy for Prolonged Ventricular Fibrillation Using a Swine Model of Sudden Cardiac Arrest.

    Science.gov (United States)

    Mader, Timothy J; Coute, Ryan A; Kellogg, Adam R; Nathanson, Brian H

    2016-01-01

    Despite experimental evidence supporting the use of resuscitation drugs in the treatment of sudden cardiac arrest (CA), there are no good human clinical data to support the decades-old practice of giving these medications during out-of-hospital CA resuscitation. We hypothesized that the lack of efficacy in clinical practice in ventricular fibrillation (VF) is the failure-based manner in which resuscitation drugs have historically been administered (one at a time interspersed with chest compressions and a defibrillation attempt, giving the next only if the previous one was ineffective). The aim of this study was to determine if giving and circulating a combination of commonly available, historically used resuscitation drugs together, prior to the first defibrillation attempt after prolonged VF, might improve short-term outcomes compared with the failure-based serial drug approach used in the past. We used a well-established swine model of sudden prolonged untreated VF. Animals were randomized to receive epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), and sodium bicarbonate (1.0 mEq/kg) in series (SERIES group [n = 53]) or a combination of epinephrine (0.01 mg/kg), vasopressin (0.5 U/kg), amiodarone (4 mg/kg), sodium bicarbonate (1.0 mEq/kg), and metoprolol (0.2 mg/kg) (COCKTAIL group) delivered in rapid succession at the beginning of the attempted resuscitation (n = 27). Data were analyzed descriptively. Baseline characteristics and chemistries between the two groups were the same. Termination of VF was statistically similar in the two groups: 88.7% (47/53) versus 85.2% (23/27) p = 0.66, with an adjusted relative risk ratio (RRR) of 0.94 (0.37, 1.15). However, ROSC was higher in the SERIES group (56.6% [30/53] versus 22.2% [6/27], adjusted RRR = 2.83; [1.16, 3.84] p = 0.029) as was 20-minute survival (52.8% [28/53] versus 18.5% [5/27], adjusted RRR = 3.15 [1.14, 4.54] p = 0.032). The combination of drugs studied, at these dosages

  13. Nilotinib alone or in combination with selumetinib is a drug candidate for neurofibromatosis type 2

    OpenAIRE

    Ammoun, Sylwia; Schmid, Marei Caroline; Triner, Joceline; Manley, Paul; Hanemann, Clemens Oliver

    2011-01-01

    Loss of the tumor suppressor merlin is a cause of frequent tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas, which occur spontaneously or as part of neurofibromatosis type 2 (NF2). Because there is medical need for drug therapies for these tumors, our aim is to find therapeutic targets. We have studied the pathobiology of schwannomas, because they are the most common merlin-deficient tumors and are a model for all merlin-deficient tumors. With use of a human sch...

  14. Experimental design and sample size determination for testing synergism in drug combination studies based on uniform measures.

    Science.gov (United States)

    Tan, Ming; Fang, Hong-Bin; Tian, Guo-Liang; Houghton, Peter J

    2003-07-15

    In anticancer drug development, the combined use of two drugs is an important strategy to achieve greater therapeutic success. Often combination studies are performed in animal (mostly mice) models before clinical trials are conducted. These experiments on mice are costly, especially with combination studies. However, experimental designs and sample size derivations for the joint action of drugs are not currently available except for a few cases where strong model assumptions are made. For example, Abdelbasit and Plackett proposed an optimal design assuming that the dose-response relationship follows some specified linear models. Tallarida et al. derived a design by fixing the mixture ratio and used a t-test to detect the simple similar action. The issue is that in reality we usually do not have enough information on the joint action of the two compounds before experiment and to understand their joint action is exactly our study goal. In this paper, we first propose a novel non-parametric model that does not impose such strong assumptions on the joint action. We then propose an experimental design for the joint action using uniform measure in this non-parametric model. This design is optimal in the sense that it reduces the variability in modelling synergy while allocating the doses to minimize the number of experimental units and to extract maximum information on the joint action of the compounds. Based on this design, we propose a robust F-test to detect departures from the simple similar action of two compounds and a method to determine sample sizes that are economically feasible. We illustrate the method with a study of the joint action of two new anticancer agents: temozolomide and irinotecan. PMID:12820275

  15. An evaluation of medetomidine/ketamine and other drug combinations for anaesthesia in cats.

    Science.gov (United States)

    Verstegen, J; Fargetton, X; Donnay, I; Ectors, F

    1991-01-12

    The anaesthesia induced by cyclohexylamine derivatives in cats was studied by comparing the effects induced by four pairs of agents: acepromazine/ketamine, xylazine/ketamine, zolazepam/tiletamine and medetomidine/ketamine. Acepromazine/ketamine was free of undesirable side effects but provided inadequate anaesthetic cover. The other combinations differed only in the dosage, the quality of the anaesthesia and the importance of the side effects. Medetomidine/ketamine was the best combination; it induced a good degree of anaesthesia with small doses and was free of major side effects. PMID:2017841

  16. Results of surgical treatment of regional cervical cancer cytotoxic drugs with when combined radiation therapy

    International Nuclear Information System (INIS)

    In the department of clinical radio oncology brachytherapy unit of the National Cancer Institute con-ducted combined radiotherapy 103 patients with cervical cancer stage IIB-IIIB cancer. Depending on the method of combined radiotherapy patients divided into 2 major (33 and 34 patients) and control (36 patients) group. In the study group patients underwent conformal radiotherapy and brachytherapy sources of high activity dose radiation (HDR). In the study group I patients during radiotherapy combined tegafur used orally in radiomodifying dose of 800 mg per day and cisplatin intravenously 50 mg 1 time per week to a total dose of 200-300 mg. In the control group patients underwent conventional external beam radiotherapy and brachytherapy sources intermediate dose radiation (MDR). Use chemoradiomodification facilities and modern radiotherapy in patients with cervical cancer helps to speed up the pace and increase the degree of regression of cervical cancer compared to the standard method of combined radiotherapy does not increase the frequency and manifestations of general and local toxicity of treatment

  17. Therapeutic Efficacy of Combining PEGylated Liposomal Doxorubicin and Radiofrequency (RF) Ablation: Comparison between Slow-Drug-Releasing, Non-Thermosensitive and Fast-Drug-Releasing, Thermosensitive Nano-Liposomes

    OpenAIRE

    Andriyanov, Alexander V.; Erez Koren; Yechezkel Barenholz; S Nahum Goldberg

    2014-01-01

    AIMS: To determine how the accumulation of drug in mice bearing an extra-hepatic tumor and its therapeutic efficacy are affected by the type of PEGylated liposomal doxorubicin used, treatment modality, and rate of drug release from the liposomes, when combined with radiofrequency (RF) ablation. MATERIALS AND METHODS: Two nano-drugs, both long-circulating PEGylated doxorubicin liposomes, were formulated: (1) PEGylated doxorubicin in thermosensitive liposomes (PLDTS), having a burst-type fast d...

  18. The use of combined spinal-epidural technique to compare intrathecal ziconotide and epidural opioids for trialing intrathecal drug delivery.

    Science.gov (United States)

    Gulati, Amitabh; Loh, Jeffrey; Puttanniah, Vinay; Malhotra, Vivek

    2013-03-01

    SUMMARY Choosing the initial medications for intrathecal delivery is often confusing and not standardized. We describe a novel way for using a combined spinal-epidural technique to compare two first-line medications for intrathecal delivery; ziconotide and morphine (or hydromorphone). Five patients with intractable chronic or cancer pain were elected to have an intrathecal drug delivery system implanted for pain management. Each patient was given a 3-day inpatient trial with the combined spinal-epidural technique. The Visual Analog Scale, Numerical Rating Scale, short-term McGill questionnaire and opioid consumption were monitored daily. The results were used to develop a paradigm to describe how ziconotide can be used in practice. PMID:24645996

  19. Progress in Using Combination of Chinese Drug with Chemotherapy to Treat Cancer

    Institute of Scientific and Technical Information of China (English)

    贺用和

    2004-01-01

    @@ Traditional Chinese medicine (TCM) has been used to treat diseases including cancer in China for several thousand years. TCM holds that the pathogenesis of cancer lies mainly in deficiency of vital qi, accumulation of cold, stagnation of qi, obstruction of phlegm, blood stasis, retention of toxic heat, and that the therapeutic principles for cancer should be mainly to strengthen body resistance and restore normal function (mainly by strengthening the spleen and nourishing the kidney), to warm yang and disperse cold, to soothe the liver and regulate qi circulation, to resolve phlegm and dispel retained water, to promote blood circulation and remove blood stasis, to clear away heat and remove toxicity, to resolve hard mass and to treat malignant or poisoning diseases with poisonous drugs.

  20. Importance of the long-acting partner drug in artemisinin-based combination therapy.

    Science.gov (United States)

    Kurtzhals, Jørgen Al

    2008-11-01

    The 1st African Health Research Organization International Malaria Symposium on Clinical Pharmacology of Antimalarial Drugs collected approximately 60 health professionals, scientists, policy makers and nongovernmental organization representatives from Africa, Europe and the USA for updates on recent developments in malaria therapy. It was the first African Health Research Organization symposium in Africa aimed at taking an African leadership in the fight against malaria. The intention is to start a tradition of annually recurring symposia that will eventually grow to become a leading international event in malaria research. Apart from scientific presentations, substantial time was dedicated to discussions and brainstorming, with a view to developing tools that can realistically be used to address challenges relating to all aspects of malaria treatment and control. The meeting was funded partly by the Medicines for Malaria Venture and Dafra Pharma International Ltd., Belgium, both of which were represented by some of the speakers. PMID:24410604

  1. Gold Nanorods Conjugated with Doxorubicin and cRGD for Combined Anticancer Drug Delivery and PET Imaging

    Directory of Open Access Journals (Sweden)

    Yuling Xiao, Hao Hong, Vyara Z. Matson, Alireza Javadi, Wenjin Xu, Yunan Yang, Yin Zhang, Jonathan W. Engle, Robert J. Nickles, Weibo Cai, Douglas A. Steeber, Shaoqin Gong

    2012-01-01

    Full Text Available A multifunctional gold nanorod (GNR-based nanoplatform for targeted anticancer drug delivery and positron emission tomography (PET imaging of tumors was developed and characterized. An anti-cancer drug (i.e., doxorubicin (DOX was covalently conjugated onto PEGylated (PEG: polyethylene glycol GNR nanocarriers via a hydrazone bond to achieve pH-sensitive controlled drug release. Tumor-targeting ligands (i.e., the cyclo(Arg-Gly-Asp-D-Phe-Cys peptides, cRGD and 64Cu-chelators (i.e., 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA were conjugated onto the distal ends of the PEG arms to achieve active tumor-targeting and PET imaging, respectively. Based on flow cytometry analysis, cRGD-conjugated nanocarriers (i.e., GNR-DOX-cRGD exhibited a higher cellular uptake and cytotoxicity than non-targeted ones (i.e., GNR-DOX in vitro. However, GNR-DOX-cRGD and GNR-DOX nanocarriers had similar in vivo biodistribution according to in vivo PET imaging and biodistribution studies. Due to the unique optical properties of GNRs, this multifunctional GNR-based nanoplatform can potentially be optimized for combined cancer therapies (chemotherapy and photothermal therapy and multimodality imaging (PET, optical, X-ray computed tomography (CT, etc..

  2. Light-controlled drug releasing polymer films combining LbL self-assembly and host-guest interactions

    Directory of Open Access Journals (Sweden)

    J. Li

    2014-03-01

    Full Text Available By combining LbL (layer-by-layer self-assembly approach and host-guest interactions, a unique multilayer film was constructed and employed for a light-controlled drug release system. The drug molecules can be loaded and released into the resulting polyelectrolyte multilayers containing azobenzene (Azo function groups by using the irradiation of visible light and UV light alternately. The photo-sensitivity of the multilayer films was studied through UV-vis spectrum, fluorescence spectrum and confocal microscopy. The target molecules could be rapidly released from the multilayers after 300 W UV light irradiation for 20 minutes. Moreover, they could be readsorbed into the multilayers uniformly when illuminated under the 300 W visible light for 10 minutes confirmed by the observation of confocal microscopy, and the readsorption ratio exceeds 100% evidenced from UV–vis spectroscopy. After several cycles of the above-mentioned process, the multilayer films show good fatigue resistance. All these results indicate the photo-sensitivity and high-efficiency of the multilayer films, which have great potential in controlled drug delivery platform and biomedical applications.

  3. Combinations of protein-chemical complex structures reveal new targets for established drugs.

    OpenAIRE

    Kalinina, Olga V.; Oliver Wichmann; Gordana Apic; Russell, Robert B.

    2011-01-01

    Biological networks are powerful tools for predicting undocumented relationships between molecules. The underlying principle is that existing interactions between molecules can be used to predict new interactions. Here we use this principle to suggest new protein-chemical interactions via the network derived from three-dimensional structures. For pairs of proteins sharing a common ligand, we use protein and chemical superimpositions combined with fast structural compatibility screens to predi...

  4. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

    DEFF Research Database (Denmark)

    Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank;

    2011-01-01

    The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration....

  5. Hyperbaric oxygen combined with drug therapy in the treatment of acute cerebral infarction clinical analysis

    Institute of Scientific and Technical Information of China (English)

    Wen-Cui Lin; Kang Lin; Jing Wang; Shuai Li

    2015-01-01

    Objective:To explore the effects of hyperbaric oxygen combined with edaravone, salviae miltiorrhizae and ligustrazine and sodium ozagrel in the treatment of acute cerebral infarction clinical analysis.Methods: A total of 200 cases of acute cerebral infraction patients were randomly divided into observation group and control group. The control group was treated with edaravone, salvia miltiorrhizae and ligustrazine and sodium ozagrel; on the basis of treatment in control group, the observation group was combined with hyperbaric oxygen therapy. The neurological deficit scores were observed before and after treatment in patients of two groups, meanwhile the activities of daily living (ADL) and clinical effects were compared.Results: The total effective rate in observation group (92%) was significantly higher than control group (79%), the differences were statistically significant; the score of ADL in observation group after treatment was obviously higher than control group [(79.91±5.16)vs (61.62±5.60)], and the differences were statistically significant. The neurological deficit scores after treatment were obviously lower than the control group [(9.55±4.13)vs (15.46±4.92)], the differences were statistically significant.Conclusion: Hyperbaric oxygen combined with edaravone, salvia miltiorrhizae and ligustrazine and sodium ozagrel in the treatment of acute cerebral infarction can improve the symptoms of microcirculation and neurologic impairment, and improve the patient s quality of life.

  6. Development of an HPLC-UV Method for the Analysis of Drugs Used for Combined Hypertension Therapy in Pharmaceutical Preparations and Human Plasma

    OpenAIRE

    Serife Evrim Kepekci Tekkeli

    2013-01-01

    A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML), olmesartan medoxomil (OLM), valsartan (VAL), and hydrochlorothiazide (HCT) in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I) and AML, VAL, and HCT (combination II). The separation...

  7. Associação de medicamentos: estatinas e fibratos Combination of drugs: statins and fibrates

    Directory of Open Access Journals (Sweden)

    Hermes Toros Xavier

    2005-10-01

    Full Text Available Monoterapia para o tratamento das dislipidemias é frequentemente insuficiente para o alcance das metas recomendadas pelas diretrizes. Entretanto, nos últimos anos, o uso de terapia combinada tem se apresentado como uma nova opção em muitos casos. Uma revisão de 36 estudos envolvendo a combinação de estatinas com fibratos apresentou 29 casos de rabdomiólise e uma prevalência geral de miopatia de 0,12%. A combinação de estatinas com o genfibrozil parece causar mais rabdomiólise que com os fibratos de nova geração (especialmente quando comparado com fenofibrato ou bezafibrato. Idade avançada, diabetes, mulheres, medicações concomitantes, disfunção renal, consumo excessivo de álcool, exercícios, traumatismos e cirurgias estão também associados com maior risco de efeitos adversos.Monotherapy for the treatment of dyslipidemias is commonly insufficient to achieve all lipid targets recommended by current guidelines. Therefore, the use of combined treatment has emerged as a new option in many cases in the last few years. A review of 36 studies in which the combination of statins with fibrates was used revealed 29 cases of rhabdomyolysis with a prevalence of 0,12% in the risk of myopathy. Combination of a statin with genfibrozil appeared to cause more rhabdomyolysis than with newest fibrates (especially when compared with fenofibrate or bezafibrate. Advanced age, diabetes, females, concomitant medications, renal insufficiency, excess in alcohol intake, exercises, trauma and surgery were all associated with higher rates of adverse effects.

  8. Pain and anxiety management for pediatric dental procedures using various combinations of sedative drugs: A review.

    Science.gov (United States)

    Gazal, Giath; Fareed, Wamiq Musheer; Zafar, Muhammad Sohail; Al-Samadani, Khalid H

    2016-07-01

    For fearful and uncooperative children behavioral management techniques are used. In order to control the pain and anxiety in pedodontic patients, pharmacologic sedation, anesthesia and analgesia are commonly used. Midazolam is commonly used as an oral sedation agent in children; it has several features such as safety of use, quick onset and certain degree of amnesia that makes it a desirable sedation agent in children. This review paper discusses various aspects of oral midazolam, ketamine and their combinations in conscious sedation including, advantages of oral route of sedation, pharmacokinetics, range of oral doses, and antagonists for clinical dental treatment procedures. PMID:27330369

  9. [Combined analgetic drug treatment with ibuprofen after 3rd molar osteotomy].

    Science.gov (United States)

    Schmelzeisen, R; Buchweitz, I K; Fricke, A; Frölich, J

    1990-01-01

    In a placebo-controlled double-blind study using 3 x 400 mg ibuprofen during the surgical removal of impacted and dislocated third molars, a pain reduction of 64% (p = 0.05) as against the placebo control group could be demonstrated on the day of surgery and the first postoperative day. In view of the published results of a double-blind study on the reduction of cheek swelling using dexamethasone, the perioperative combination of 3 x 600 mg ibuprofen with 2 x 6 mg dexamethasone seems to be helpful in reliably preventing pain and swelling after dental surgery. PMID:2135254

  10. Antibacterial efficacy and drug-induced tooth discolouration of antibiotic combinations for endodontic regenerative procedures.

    Science.gov (United States)

    Mandras, N; Roana, J; Allizond, V; Pasqualini, D; Crosasso, P; Burlando, M; Banche, G; Denisova, T; Berutti, E; Cuffini, A M

    2013-01-01

    Elimination of microbial contamination from the root canal system is a precondition for successful root canal treatment. Teeth with immature root development, necrotic pulps and apical periodontitis present multiple challenges for successful treatment. Disinfection is achieved by irrigation followed by the placement of an intracanal medicament. A mixture of ciprofloxacin, metronidazole and minocycline (3-MIX S) has been shown to be very effective in eliminating endodontic pathogens in vitro and in vivo. Among the components of the mixture, minocycline can induce tooth discolouration after long-term oral use. Therefore, the elimination of minocycline from the above-mentioned combination has been suggested to prevent the occasion of this undesirable effect. The aim of this study was to investigate the potential antimicrobial efficacy of alternative antibiotic combinations [3-MIX C (clarithromycin); 3-MIX F (fosfomycin)] against bacteria from infected root canals. An additional objective was to evaluate their discolouration potential as possible alternatives to minocycline-based intracanal medicaments. Our in vitro results clearly demonstrated that 3-MIX C and 3-MIX F had a greater antimicrobial activity than 3-MIX S, underlying that clarithromycin still had a higher capacity to kill endodontic pathogens in vitro compared to fosfomycin. Both 3-MIX C and 3-MIX F were able to avoid the permanent staining effect of the crown. PMID:23755774

  11. HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis

    International Nuclear Information System (INIS)

    Numerous reports now indicate that HIV patients administered long-term antiretroviral therapy (ART) are at a greater risk for developing cardiovascular diseases. Endothelial dysfunction is an initiating event in atherogenesis and may contribute to HIV-associated atherosclerosis. We previously reported that ART induces direct endothelial dysfunction in rodents. In vitro treatment of human umbilical vein endothelial cells (HUVEC) with ART indicated endothelial mitochondrial dysfunction and a significant increase in the production of reactive oxygen species (ROS). In this study, we determined whether ART-induced endothelial dysfunction is mediated via mitochondria-derived ROS and whether this mitochondrial injury culminates in endothelial cell apoptosis. Two major components of ART combination therapy, a nucleoside reverse transcriptase inhibitor and a protease inhibitor, were tested, using AZT and indinavir as representatives for each. Microscopy utilizing fluorescent indicators of ROS and mitochondria demonstrated the mitochondrial localization of ART-induced ROS. MnTBAP, a cell-permeable metalloporphyrin antioxidant, abolished ART-induced ROS production. As a final step in confirming the mitochondrial origin of the ART-induced ROS, HUVEC were transduced with a cytosolic- compared to a mitochondria-targeted catalase. Transduction with the mitochondria-targeted catalase was more effective than cytoplasmic catalase in inhibiting the ROS and 8-isoprostane (8-iso-PGF2α) produced after treatment with either AZT or indinavir. However, both mitochondrial and cytoplasmic catalase attenuated ROS and 8-iso-PGF2α production induced by the combination treatment, suggesting that in this case, the formation of cytoplasmic ROS may also occur, and thus, that the mechanism of toxicity in the combination treatment group may be different compared to treatment with AZT or indinavir alone. Finally, to determine whether ART-induced mitochondrial dysfunction and ROS production culminate

  12. Capture and immobilisation of aardvark (Orycteropus afer using different drug combinations : research communication

    Directory of Open Access Journals (Sweden)

    P.J. Nel

    2000-07-01

    Full Text Available Nine aardvarks (Orycteropus afer were captured in the southern Free State, South Africa, for the placement of abdominal radio transmitters. Five combinations of ketamine hydrochloride with xylazine hydrochloride, midazolam or medetomidine hydrochloride were used to induce anaesthesia. In some cases the level of anaesthesia was maintained with 1.5 % halothane. A mixture of ketamine hydrochloride and medetomidine hydrochloride was found to be most effective. Atipamizole reversed the affects of medetomidine hydrochloride, resulting in a smooth and full recovery within 8 minutes. The immobilisation and subsequent anaesthesia of these animals on cold winter nights resulted in hypothermia, and keeping the animals warm was essential to the success of the procedures undertaken. Reversal of the sedative medetomidine hydrochloride proved to be important, because animals that were released before they were fully conscious took refuge in their burrows so that care was impossible.

  13. Tumor-Homing and Penetrating Peptide-Functionalized Photosensitizer-Conjugated PEG-PLA Nanoparticles for Chemo-Photodynamic Combination Therapy of Drug-Resistant Cancer.

    Science.gov (United States)

    Feng, Xingye; Jiang, Di; Kang, Ting; Yao, Jianhui; Jing, Yixian; Jiang, Tianze; Feng, Jingxian; Zhu, Qianqian; Song, Qingxiang; Dong, Nan; Gao, Xiaoling; Chen, Jun

    2016-07-20

    The combination of photodynamic therapy (PDT) and chemotherapy holds great potential in combating drug-resistant cancers. However, the major challenge that lies ahead is how to achieve high coloading capacity for both photosensitizer and chemo-drugs and how to gain efficient delivery of drugs to the drug-resistant tumors. In this study, we prepared a nanovehicle for codelivery of photosensitizer (pyropheophorbide-a, PPa) and chemo-drugs (paclitaxel, PTX) based on the synthesis of PPa-conjugated amphiphilic copolymer PPa-PLA-PEG-PLA-PPa. The obtained nanoparticles (PP NP) exhibited a satisfactory high drug-loading capacity for both drugs. To achieve effective tumor-targeting therapy, the surface of PP NP was decorated with a tumor-homing and penetrating peptide F3. In vitro cellular experiments showed that F3-functionalized PP NP (F3-PP NP) exhibited higher cellular association than PP NP and resulted in the strongest antiproliferation effect. In addition, compared with the unmodified nanoparticles, F3-PP NP exhibited a more preferential enrichment at the tumor site. Pharmacodynamics evaluation in vivo demonstrated that a longer survival time was achieved by the tumor-bearing mice treated with PP NP (+laser) than those treated with chemotherapy only or PDT only. Such antitumor efficacy of combination therapy was further improved following the F3 peptide functionalization. Collectively, these results suggested that targeted combination therapy may pave a promising way for the therapy of drug-resistant tumor. PMID:27332148

  14. Possibilities of the combined use of non-steroidal anti-inflammatory drugs and sulfhydryl compounds in radioprotection

    International Nuclear Information System (INIS)

    The combined preirradiation administration of indomethacin and cystamine was found to enhance synergistically the recovery of hemopoiesis in sublethally gamma-irradiated mice. This effect can be explained by a common operation of two mechanisms of radioprotection, i.e. of an increased survival of hemopoietic stem cells due to cystamine action and of stimulatory effects of indomethacin on the proliferation of surviving cells, mediated by the inhibition of prostaglandin synthesis. Attempts to prove such enhancement of protective effects on irradiated mice in terms of postirradiation lethality were unsuccessful. The reason seems to be the influence of toxic effects of the indomethacin-cystamine combination on the gastrointestinal tract. When using the less toxic combination, i.e. diclofenac and WR-2721, the additivity of protective effects is manifested even in the survival of lethally irradiated mice. The results suggest that under suitable conditions avoiding the unfavourable toxic effects, non-steroidal anti-inflammatory drugs can be successfully used with the aim to enhance the efficiency of sulfhydryl radioprotectors. (orig.)

  15. Evaluation of activity and combination strategies with the microtubule-targeting drug sagopilone in breast cancer cell lines.

    Science.gov (United States)

    Eschenbrenner, Julia; Winsel, Sebastian; Hammer, Stefanie; Sommer, Anette; Mittelstaedt, Kevin; Drosch, Michael; Klar, Ulrich; Sachse, Christoph; Hannus, Michael; Seidel, Monika; Weiss, Bertram; Merz, Claudia; Siemeister, Gerhard; Hoffmann, Jens

    2011-01-01

    Sagopilone, a fully synthetic epothilone, is a microtubule-stabilizing agent optimized for high in vitro and in vivo activity against a broad range of tumor models, including those resistant to paclitaxel and other systemic treatments. Sagopilone development is accompanied by translational research studies to evaluate the molecular mode of action, to recognize mechanisms leading to resistance, to identify predictive response biomarkers, and to establish a rationale for combination with different therapies. Here, we profiled sagopilone activity in breast cancer cell lines. To analyze the mechanisms of mitotic arrest and apoptosis and to identify additional targets and biomarkers, an siRNA-based RNAi drug modifier screen interrogating 300 genes was performed in four cancer cell lines. Defects of the spindle assembly checkpoint (SAC) were identified to cause resistance against sagopilone-induced mitotic arrest and apoptosis. Potential biomarkers for resistance could therefore be functional defects like polymorphisms or mutations in the SAC, particularly in the central SAC kinase BUB1B. Moreover, chromosomal heterogeneity and polyploidy are also potential biomarkers of sagopilone resistance since they imply an increased tolerance for aberrant mitosis. RNAi screening further demonstrated that the sagopilone-induced mitotic arrest can be enhanced by concomitant inhibition of mitotic kinesins, thus suggesting a potential combination therapy of sagopilone with a KIF2C (MCAK) kinesin inhibitor. However, the combination of sagopilone and inhibition of the prophase kinesin KIF11 (EG5) is antagonistic, indicating that the kinesin inhibitor has to be highly specific to bring about the required therapeutic benefit. PMID:22649765

  16. Development of LC Method for the Simultaneous Determination of Antidepressant Drug Combination Melitracen Hydrochloride and Flupentixol Dihydrochloride in their Combined Dosage Form

    Directory of Open Access Journals (Sweden)

    Usmangani K. Chhalotiya

    2011-01-01

    Full Text Available A simple, specific and stability-indicating reversed-phase high-performance liquid chromatographic method was developed for the simultaneous determination of melitracen hydrochloride and flupentixol dihydrochloride in tablet dosage form. A Brownlee C-18, 5 μm column having 250×4.6 mm i.d. in isocratic mode, with mobile phase containing 0.025 M potassium dihydrogen phosphate: methanol (10 : 90, v/v; pH 7.3 was used. The flow rate was 1.0 mL/min, and effluents were monitored at 230 nm. The retention times of melitracen hydrochloride and flupentixol dihydrochloride were 7.75 min and 5.50 min, respectively. The linearity for melitracen hydrochloride and flupentixol dihydrochloride were in the range of 0.5–60 μg/mL. The recoveries obtained for melitracen hydrochloride and flupenthixol dihydrochloride was 99.81–100.77% and 99.42–100.12%, respectively. Both the drugs were subjected to acid and alkali hydrolysis, chemical oxidation, and dry heat degradation and photodegradation. The proposed method was validated and successfully applied to the estimation of melitracen hydrochloride and flupentixol dihydrochloride in combined tablet dosage form.

  17. Survey of pharmacists and physicians on drug interactions between combined oral contraceptives and broad-spectrum antibiotics

    Directory of Open Access Journals (Sweden)

    Masters KP

    2009-09-01

    Full Text Available Objective: To evaluate physician and pharmacist knowledge on potential drug interactions between combined oral contraceptives (COC and broad-spectrum antibiotics and determine if any difference exists between responses.Methods: Two hundred licensed retail pharmacists and 200 licensed family practice physicians in the states of Virginia, West Virginia, and Maryland were mailed an anonymous survey between August 2007 and November 2007. The survey consisted of 3 short questions asking practitioners about their current opinion on drug interactions with COCs and whether an alternative form of contraception is needed for patients taking COC and concomitant broad-spectrum antibiotics. The main outcome measure of the survey included: identifying how physicians and pharmacists handle prescribing or dispensing COCs along with broad-spectrum antibiotics. Gender, educational degree, and years in practice were also collected. Results: A total of 182 participants returned the surveys (57% were physicians and 43% were pharmacists. When asked if broad-spectrum antibiotics have a clinically significant interaction with COCs, 82.7% of physicians and 88.5% of pharmacists answered, “yes”. Of the respondents, 84.6% stated that the drug interaction warrants the patient to be advised to use back-up contraception. A total of 90.1% stated that they currently instruct patients to use back-up contraception when prescribing or dispensing antibiotics to a patient who is on COC, with no statistically significant difference existing between the responses of the pharmacists and the physicians.Conclusion: Physicians and pharmacists believe that broad-spectrum antibiotics decrease the effectiveness of COCs. These practitioners warn their patients of this interaction and advise the use of back-up contraception. More education should be provided to practitioners regarding the data concerning COCs and broad spectrum antibiotics and lack of a proven interaction.

  18. Observation on 105 Cases of Duodenal Bulbar Ulcer Treated by Combined Therapy of Catgut Embedding and Chinese Drugs

    Institute of Scientific and Technical Information of China (English)

    范兆金

    2001-01-01

    @@Duodenal bulbar ulcer is a frequently encountered disease. Clinically, it manifests itself by regular epigastric pain accompanied by belching and acid regurgitation, corresponding to epigastralgia and stomach distending pain in traditional Chinese medicine (TCM). Based on the TCM type-differentiation, the author has treated 105 cases of duodenal bulbar ulcer by the combined therapy of catgut embedding at point Zusanli (ST 36) and Chinese drugs with satisfactory results. A summary is as follows. Clinical Data 1. Case selection: The cases selected all had the clinical symptoms and signs of duodenal bulbar ulcer, and had been diagnosed by GI examination at this or other hospitals with no obvious therapeutic effects obtained after relevant treatment, and still symptoms and signs and repeated attacks of pain.

  19. Drug quantification in turbid media by fluorescence imaging combined with light-absorption correction using white Monte Carlo simulations

    DEFF Research Database (Denmark)

    Xie, Haiyan; Liu, Haichun; Svenmarker, Pontus; Axelsson, Johan; Xu, Can T.; Gräfe, Susanna; Lundeman, Jesper Holm; Cheng, Haynes Pak Hay; Svanberg, Sune; Bendsoe, Niels; Andersen, Peter E.; Svanberg, Katarina; Andersson-Engels, Stefan

    2011-01-01

    light by turbid media, such as biological tissue, the detected fluorescence signal does not have a simple and unique dependence on the fluorophore concentration for different tissues, but depends in a complex way on other parameters as well. For this reason, little has been done on drug quantification...... in vivo by the fluorescence imaging technique. In this paper we present a novel approach to compensate for the light absorption in homogeneous turbid media both for the excitation and emission light, utilizing time-resolved fluorescence white Monte Carlo simulations combined with the Beer-Lambert law....... This method shows that the corrected fluorescence intensity is almost proportional to the absolute fluorophore concentration. The results on controllable tissue phantoms and murine tissues are presented and show good correlations between the evaluated fluorescence intensities after the light...

  20. Identifying New Drug Targets for Potent Phospholipase D Inhibitors: Combining Sequence Alignment, Molecular Docking, and Enzyme Activity/Binding Assays.

    Science.gov (United States)

    Djakpa, Helene; Kulkarni, Aditya; Barrows-Murphy, Scheneque; Miller, Greg; Zhou, Weihong; Cho, Hyejin; Török, Béla; Stieglitz, Kimberly

    2016-05-01

    Phospholipase D enzymes cleave phospholipid substrates generating choline and phosphatidic acid. Phospholipase D from Streptomyces chromofuscus is a non-HKD (histidine, lysine, and aspartic acid) phospholipase D as the enzyme is more similar to members of the diverse family of metallo-phosphodiesterase/phosphatase enzymes than phospholipase D enzymes with active site HKD repeats. A highly efficient library of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure was utilized to evaluate the inhibition of purified S. chromofuscus phospholipase D. The molecules exhibited inhibition of phospholipase D activity (IC50 ) in the nanomolar range with monomeric substrate diC4 PC and micromolar range with phospholipid micelles and vesicles. Binding studies with vesicle substrate and phospholipase D strongly indicate that these inhibitors directly block enzyme vesicle binding. Following these compelling results as a starting point, sequence searches and alignments with S. chromofuscus phospholipase D have identified potential new drug targets. Using AutoDock, inhibitors were docked into the enzymes selected from sequence searches and alignments (when 3D co-ordinates were available) and results analyzed to develop next-generation inhibitors for new targets. In vitro enzyme activity assays with several human phosphatases demonstrated that the predictive protocol was accurate. The strategy of combining sequence comparison, docking, and high-throughput screening assays has helped to identify new drug targets and provided some insight into how to make potential inhibitors more specific to desired targets. PMID:26691755

  1. Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

    Science.gov (United States)

    Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

    2015-04-01

    The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing). PMID:25273028

  2. ADMET Evaluation in Drug Discovery. 16. Predicting hERG Blockers by Combining Multiple Pharmacophores and Machine Learning Approaches.

    Science.gov (United States)

    Wang, Shuangquan; Sun, Huiyong; Liu, Hui; Li, Dan; Li, Youyong; Hou, Tingjun

    2016-08-01

    Blockade of human ether-à-go-go related gene (hERG) channel by compounds may lead to drug-induced QT prolongation, arrhythmia, and Torsades de Pointes (TdP), and therefore reliable prediction of hERG liability in the early stages of drug design is quite important to reduce the risk of cardiotoxicity-related attritions in the later development stages. In this study, pharmacophore modeling and machine learning approaches were combined to construct classification models to distinguish hERG active from inactive compounds based on a diverse data set. First, an optimal ensemble of pharmacophore hypotheses that had good capability to differentiate hERG active from inactive compounds was identified by the recursive partitioning (RP) approach. Then, the naive Bayesian classification (NBC) and support vector machine (SVM) approaches were employed to construct classification models by integrating multiple important pharmacophore hypotheses. The integrated classification models showed improved predictive capability over any single pharmacophore hypothesis, suggesting that the broad binding polyspecificity of hERG can only be well characterized by multiple pharmacophores. The best SVM model achieved the prediction accuracies of 84.7% for the training set and 82.1% for the external test set. Notably, the accuracies for the hERG blockers and nonblockers in the test set reached 83.6% and 78.2%, respectively. Analysis of significant pharmacophores helps to understand the multimechanisms of action of hERG blockers. We believe that the combination of pharmacophore modeling and SVM is a powerful strategy to develop reliable theoretical models for the prediction of potential hERG liability. PMID:27379394

  3. Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats

    Institute of Scientific and Technical Information of China (English)

    CHANG Qing; LIU Zhe; MA Wen-zhi; HEI Chang-chun; SHEN Xin-sheng; QIAN Xiao-jing; XU Zeng-lu

    2011-01-01

    Background Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen.Methods Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight,volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods.Results Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH.Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group.Conclusions The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal sperm.

  4. Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot.

    Science.gov (United States)

    Kim, Da Yeon; Kwon, Doo Yeon; Kwon, Jin Seon; Park, Ji Hoon; Park, Seung Hun; Oh, Hyun Ju; Kim, Jae Ho; Min, Byoung Hyun; Park, Kinam; Kim, Moon Suk

    2016-04-01

    Here, we describe combinational chemotherapy via intratumoral injection of doxorubicin (Dox) and 5-fluorouracil (Fu) to enhance the efficacy and reduce the toxicity of systemically administered Fu and Dox in cancer patients. As the key concept in this work, mixture formulations of Dox-loaded microcapsules (Dox-M) and Fu-loaded Pluronic(®) hydrogels (Fu-HP) or Fu-loaded diblock copolymer hydrogels (Fu-HC) have been employed as drug depots. The in vitro and in vivo drug depot was designed as a formulation of Dox-M dispersed inside an outer shell of Fu-HP or Fu-HC after injection. The Dox-M/Fu-HP and Dox-M/Fu-HC formulations are free flowing at room temperature, indicating injectability, and formed a structural gelatinous depot in vitro and in vivo at body temperature. The Fu-HP, Fu-HC, Dox-M/Fu-HP, Dox-M/Fu-HC, and Dox-M formulations were easily injected into tumor centers in mice using a needle. Dox-M/Fu-HC produced more significant inhibitory effects against tumor growth than that by Dox-M/Fu-HP, while Fu-HP, Fu-HC and Dox-M had the weakest inhibitory effects of the tested treatments. The in vivo study of Dox and Fu biodistribution showed that high Dox and Fu concentrations were maintained in the target tumor only, while distribution to normal tissues was not observed, indicating that Dox and Fu concentrations below their toxic plasma concentrations should not cause significant systemic toxicity. The Dox-M/Fu-HP and Dox-M/Fu-HC drug depots described in this work showed excellent performance as chemotherapeutic delivery systems. The results reported here indicate that intratumoral injection using combination chemotherapy with Dox-M/Fu-HP or Dox-M/Fu-HC could be of translational research by enhancing the synergistic inhibitory effects of Dox and Fu on tumor growth, while reducing their systemic toxicity in cancer patients. PMID:26874285

  5. Effect of treatment in fractionated schedules with the combination of x-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin

    International Nuclear Information System (INIS)

    RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis-diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatment in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra-additivity ratios, SR/sub I/ and SR/sub II/, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo

  6. A randomised trial to compare the safety, tolerability and efficacy of three drug combinations for intermittent preventive treatment in children.

    Directory of Open Access Journals (Sweden)

    Kalifa Bojang

    Full Text Available BACKGROUND: Results from trials of intermittent preventive treatment (IPT in infants and children have shown that IPT provides significant protection against clinical malaria. Sulfadoxine-pyrimethamine (SP given alone or in combination with other drugs has been used for most IPT programmes. However, SP resistance is increasing in many parts of Africa. Thus, we have investigated whether SP plus AQ, SP plus piperaquine (PQ and dihydroartemisinin (DHA plus PQ might be equally safe and effective when used for IPT in children in an area of seasonal transmission. METHODS: During the 2007 malaria transmission season, 1008 Gambian children were individually randomized to receive SP plus amodiaquine (AQ, SP plus piperaquine (PQ or dihydroartemisinin (DHA plus PQ at monthly intervals on three occasions during the peak malaria transmission season. To determine the risk of side effects following drug administration, participants in each treatment group were visited at home three days after the start of each round of drug administration and a side effects questionnaire completed. To help establish whether adverse events were drug related, the same questionnaire was administered to 286 age matched control children recruited from adjacent villages. Morbidity was monitored throughout the malaria transmission season and study children were seen at the end of the malaria transmission season. RESULTS: All three treatment regimens showed good safety profiles. No severe adverse event related to IPT was reported. The most frequent adverse events reported were coughing, diarrhoea, vomiting, abdominal pain and loss of appetite. Cough was present in 15.2%, 15.4% and 18.7% of study subjects who received SP plus AQ, DHA plus PQ or SP plus PQ respectively, compared to 19.2% in a control group. The incidence of malaria in the DHA plus PQ, SP plus AQ and SP plus PQ groups were 0.10 cases per child year (95% CI: 0.05, 0.22, 0.06 (95% CI: 0.022, 0.16 and 0.06 (95% CI: 0.02, 0

  7. A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops

    OpenAIRE

    Ward Lorrayne; Ipuge Yahya; Odhiambo Moses; Gross Isaac; Bishop David; Gordon Megumi; Sabot Kate; Sabot Oliver; Cohen Justin M; Mwita Alex; Goodman Catherine

    2010-01-01

    Abstract Background Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs), the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility – malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation ...

  8. Quantitative Analysis of the Anti-Proliferative Activity of Combinations of Selected Iron-Chelating Agents and Clinically Used Anti-Neoplastic Drugs

    OpenAIRE

    Eliska Potuckova; Hana Jansova; Miloslav Machacek; Anna Vavrova; Pavlina Haskova; Lucie Tichotova; Vera Richardson; Kalinowski, Danuta S.; Richardson, Des R.; Tomas Simunek

    2014-01-01

    Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, ...

  9. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

    OpenAIRE

    Hazlewood, Glen S; Barnabe, Cheryl; Tomlinson, George; Marshall, Deborah; Devoe, Dan; Bombardier, Claire

    2016-01-01

    Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. Design Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. Data sources Trials were identified from Medline, Em...

  10. A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole

    OpenAIRE

    Agnik Pal; Sukanta Sen; Suvajit Das; Arunava Biswas; Tripathi, Santanu K.

    2014-01-01

    A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but wit...

  11. Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

    Science.gov (United States)

    Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

    2016-05-01

    In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26991506

  12. Nanomedicine: nanoparticles, molecular biosensors, and targeted gene/drug delivery for combined single-cell diagnostics and therapeutics

    Science.gov (United States)

    Prow, Tarl W.; Salazar, Jose H.; Rose, William A.; Smith, Jacob N.; Reece, Lisa; Fontenot, Andrea A.; Wang, Nan A.; Lloyd, R. Stephen; Leary, James F.

    2004-07-01

    Next generation nanomedicine technologies are being developed to provide for continuous and linked molecular diagnostics and therapeutics. Research is being performed to develop "sentinel nanoparticles" which will seek out diseased (e.g. cancerous) cells, enter those living cells, and either perform repairs or induce those cells to die through apoptosis. These nanoparticles are envisioned as multifunctional "smart drug delivery systems". The nanosystems are being developed as multilayered nanoparticles (nanocrystals, nanocapsules) containing cell targeting molecules, intracellular re-targeting molecules, molecular biosensor molecules, and drugs/enzymes/gene therapy. These "nanomedicine systems" are being constructed to be autonomous, much like present-day vaccines, but will have sophisticated targeting, sensing, and feedback control systems-much more sophisticated than conventional antibody-based therapies. The fundamental concept of nanomedicine is to not to just kill all aberrant cells by surgery, radiation therapy, or chemotherapy. Rather it is to fix cells, when appropriate, one cell-at-a-time, to preserve and re-build organ systems. When cells should not be fixed, such as in cases where an improperly repaired cell might give rise to cancer cells, the nanomedical therapy would be to induce apoptosis in those cells to eliminate them without the damagin bystander effects of the inflammatory immune response system reacting to necrotic cells or those which have died from trauma or injury. The ultimate aim of nanomedicine is to combine diagnostics and therapeutics into "real-time medicine", using where possible in-vivo cytometry techniques for diagnostics and therapeutics. A number of individual components of these multi-component nanoparticles are already working in in-vitro and ex-vivo cell and tissue systems. Work has begun on construction of integrated nanomedical systems.

  13. Is the combination of cellulosic polymers and anionic surfactants a good strategy for ensuring physical stability of BCS Class II drug nanosuspensions?

    Science.gov (United States)

    Bilgili, Ecevit; Li, Meng; Afolabi, Afolawemi

    2016-01-01

    Ensuring the physical stability of drug nanosuspensions prepared via wet media milling has been a challenge for pharmaceutical scientists. The aim of this study is to assess the combined use of non-ionic cellulosic polymers and anionic surfactants in stabilizing multiple drug nanosuspensions. Particle size of five drugs, i.e. azodicarbonamide (AZD), fenofibrate (FNB), griseofulvin (GF), ibuprofen (IBU) and phenylbutazone (PB) was reduced separately in an aqueous solution of hydroxypropyl cellulose (HPC) with/without sodium dodecyl sulfate (SDS) via a stirred media mill. Laser diffraction, scanning electron microscopy, thermal analysis, rheometry and electrophoresis were used to evaluate the breakage kinetics, storage stability, electrostatic repulsion and stabilizer adsorption. Without SDS, drug particles exhibited aggregation to different extents; FNB and GF particles aggregated the most due to low zeta potential and insufficient steric stabilization. Although aggregation in all milled suspensions was reduced due to HPC-SDS combination, FNB and IBU showed notable growth during 7-day storage. It is concluded that the combination of non-ionic cellulosic polymers and anionic surfactants is generally viable for ensuring the physical stability of wet-milled drug nanosuspensions, provided that the surfactant concentration is optimized to mitigate the Ostwald ripening, whereas cellulosic polymers alone may provide stability for some drug suspensions. PMID:25774989

  14. Swelling/floating capability and drug release characterizations of gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose.

    Science.gov (United States)

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug's release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

  15. Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine.

    NARCIS (Netherlands)

    Abbate, E.; Vescovo, M.; Natiello, M.; Cufre, M.; Garcia, A.; Gonzalez Montaner, P.; Ambroggi, M.; Ritacco, V.; Soolingen, D. van

    2012-01-01

    OBJECTIVES: Current drug choices to treat extensively drug-resistant (XDR) tuberculosis (TB) are scarce; therefore, information on the safety, tolerability and efficacy of alternative regimens is of utmost importance. The aim of this study was to describe the management, drug adverse effects and out

  16. Prevalence of malaria parasitemia and purchase of artemisinin-based combination therapies (ACTs among drug shop clients in two regions in Tanzania with ACT subsidies.

    Directory of Open Access Journals (Sweden)

    Melissa A Briggs

    Full Text Available BACKGROUND: Throughout Africa, many people seek care for malaria in private-sector drug shops where diagnostic testing is often unavailable. Recently, subsidized artemisinin-based combination therapies (ACTs, a first-line medication for uncomplicated malaria, were made available in these drug shops in Tanzania. This study assessed the prevalence of malaria among and purchase of ACTs by drug shop clients in the setting of a national ACT subsidy program and sub-national drug shop accreditation program. METHOD AND FINDINGS: A cross-sectional survey of drug shop clients was performed in two regions in Tanzania, one with a government drug shop accreditation program and one without, from March-May, 2012. Drug shops were randomly sampled from non-urban districts. Shop attendants were interviewed about their education, training, and accreditation status. Clients were interviewed about their symptoms and medication purchases, then underwent a limited physical examination and laboratory testing for malaria. Malaria prevalence and predictors of ACT purchase were assessed using univariate analysis and multiple logistic regression. Amongst 777 clients from 73 drug shops, the prevalence of laboratory-confirmed malaria was 12% (95% CI: 6-18%. Less than a third of clients with malaria had purchased ACTs, and less than a quarter of clients who purchased ACTs tested positive for malaria. Clients were more likely to have purchased ACTs if the participant was 5 years, experience (aOR: 2.8; 95% CI: 1.2-6.3. Having malaria was only a predictor of ACT purchase in the region with a drug shop accreditation program (aOR: 3.4; 95% CI: 1.5-7.4. CONCLUSION: Malaria is common amongst persons presenting to drug shops with a complaint of fever. The low proportion of persons with malaria purchasing ACTs, and the high proportion of ACTs going to persons without malaria demonstrates a need to better target who receives ACTs in these drug shops.

  17. Integrin-targeting thermally cross-linked superparamagnetic iron oxide nanoparticles for combined cancer imaging and drug delivery

    Science.gov (United States)

    Yu, Mi Kyung; Park, Jinho; Jeong, Yong Yeon; Moon, Woo Kyung; Jon, Sangyong

    2010-10-01

    We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine-glycine-aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGD_TCL-SPION) had a mean hydrodynamic size of 34 ± 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGD_TCL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin αvβ3 +) when analyzed by T2-weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGD_TCL-SPION via ionic interaction, the resulting Dox-loaded cRGD_TCL-SPION (Dox@cRGD_TCL-SPION) showed much higher cytotoxicity in U87MG cells than Dox@TCL-SPION lacking cRGD (IC50 value of 0.02 µM versus 0.12 µM). These results suggest that Dox@cRGD_TCL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent.

  18. Integrin-targeting thermally cross-linked superparamagnetic iron oxide nanoparticles for combined cancer imaging and drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong [School of Life Sciences, Gwangju Institute of Science and Technology, 261 Chemdangwagi-ro, Gwangju 500-712 (Korea, Republic of); Jeong, Yong Yeon [Department of Diagnostic Radiology, Jeonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun-eup, Jeonnam 519-809 (Korea, Republic of); Moon, Woo Kyung, E-mail: syjon@gist.ac.kr [Diagnostic Radiology, Seoul National University Hospital and the Institute of Radiation Medicine, Medical Research Center Seoul National University, Seoul 110-744 (Korea, Republic of)

    2010-10-15

    We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine-glycine-aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGD{sub T}CL-SPION) had a mean hydrodynamic size of 34 {+-} 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGD{sub T}CL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin {alpha}{sub v{beta}3} +) when analyzed by T{sub 2}-weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGD{sub T}CL-SPION via ionic interaction, the resulting Dox-loaded cRGD{sub T}CL-SPION (Dox-cRGD{sub T}CL-SPION) showed much higher cytotoxicity in U87MG cells than Dox-TCL-SPION lacking cRGD (IC{sub 50} value of 0.02 {mu}M versus 0.12 {mu}M). These results suggest that Dox-cRGD{sub T}CL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent.

  19. Integrin-targeting thermally cross-linked superparamagnetic iron oxide nanoparticles for combined cancer imaging and drug delivery

    International Nuclear Information System (INIS)

    We report multifunctional nanoparticles that are capable of cancer targeting and simultaneous cancer imaging and therapy. The nanoparticles are composed of cyclic arginine-glycine-aspartic acid (cRGD) peptide ligand bioconjugated thermally cross-linked superparamagnetic iron oxide nanoparticles (TCL-SPION) that enable loading of the anticancer drug doxorubicin (Dox). The cyclic RGD-conjugated TCL-SPION (cRGDTCL-SPION) had a mean hydrodynamic size of 34 ± 8 nm with approximately 0.39 wt% of cyclic RGD attached to the surface of the nanoparticles. The cRGDTCL-SPION exhibited preferential binding towards target cancer cells (U87MG, integrin αvβ3 +) when analyzed by T2-weighted magnetic resonance (MR) imaging. When Dox was loaded onto the polymeric coating layers of cRGDTCL-SPION via ionic interaction, the resulting Dox-loaded cRGDTCL-SPION (Dox-cRGDTCL-SPION) showed much higher cytotoxicity in U87MG cells than Dox-TCL-SPION lacking cRGD (IC50 value of 0.02 μM versus 0.12 μM). These results suggest that Dox-cRGDTCL-SPION has potential for use as an integrin-targeted, combined imaging and therapeutic agent.

  20. Effects of Blood-Activating and Stasis-Removing Drugs Combined with VEGF Gene Transfer on Angiogenesis in Ischemic Necrosis of the Femoral Head

    Institute of Scientific and Technical Information of China (English)

    LI Jun-hui; WU Ya-ling; YE Jian-hong; NING Ya-gong; YU Hai-ying; PENG Zhong-jie; LUAN Xiao-wen

    2009-01-01

    Objective:To observe the promoting effects of blood-activating and stasis-removing Chinese drugs combined with vascular endothelial growth factor (VEGF) gene transfer on angiogenesis in ischemic necrosis of the femoral head.Methods:Forty Japanese giant-ear rabbits were randomly divided into a control group, a model group, a Chinese drug group, a gene group, and a combined group.After 8 weeks of treatment, the rate of VEGF positive cell expression in the synovium of the femoral head was measured using the immunohistochemical method, and the number of blood vessels in the femoral head was measured by digital subtraction angiography.Results:The rate of VEGF positive cell expression in the model group was significantly lower than that in the Chinese drug group (P<0.05) and very significantly lower than those in other groups (P<0.01);but in the combined group it was significantly higher than in the Chinese drug group (P<0.05).The differences in the number of blood vessels in area A between the model group and other groups were not statistically significant.However, in area B, the number of blood vessels significantly increased in the control group, the gene group and the combined group as compared with the model group (P<0.05), and in the combined group the number of blood vessels was significantly more than in the gene group (P<0.05);but in the Chinese drug group it was not significantly different than the model group P>0.05).Conelusion:Either the blood-activating and stasis-removing Chinese drugs or VEGF gene transfer can promote the angiogenesis and building of collateral circulation for femoral head ischemic necrosis, and the combined therapy with Chinese drugs or VEGF gene transfer may show a better therapeutic effect.The present study provides an experimental basis for clinical application of the combined therapy with the blood-activating and stasis-removing Chinese drugs and VEGF gene transfer.

  1. Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

    OpenAIRE

    Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

    2015-01-01

    The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various...

  2. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    OpenAIRE

    Pauline Byakika-Kibwika; Mohammed Lamorde; Harriet Mayanja-Kizza; Saye Khoo; Concepta Merry; Jean-Pierre Van geertruyden

    2011-01-01

    Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART) poses significant challenges. Artemether-lumefantrine (AL) is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450) enzymes which metabolize the protease inhibitors (PIs) and nonnucle...

  3. Intraocular Pressure-Lowering Effects of Commonly Used Fixed-Combination Drugs with Timolol: A Systematic Review and Meta-Analysis

    OpenAIRE

    Cheng, Jin-Wei; Cheng, Shi-Wei; Gao, Lian-Di; Lu, Guo-Cai; Wei, Rui-Li

    2012-01-01

    Background The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP), and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol. Methods Pertinent publications were identified through systematic searches. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma...

  4. The irrational fixed dose combinations in the Indian drug market: an evaluation of prescribing pattern using WHO guidelines

    Directory of Open Access Journals (Sweden)

    Somesh P. Rayasam

    2013-08-01

    Full Text Available Background: Evaluation of the pattern of fixed dose combinations (FDCs prescribing amongst the practitioners in a tertiary care hospital in Central India. Methods: Nine hundred and ninety four prescriptions, containing 639 FDCs were scrutinized in the tertiary care hospital. After excluding the total and the interdepartmental repetitions, the numbers of FDCs were 278, which were considered for final analysis. Inclusion criteria were FDCs from the major out-patient department (OPD of the tertiary care hospital from January 2011 to December 2011. FDCs from the wards, casualty, infectious disease unit, intensive cardiac care unit (ICCU, tuberculosis and chest and HIV unit were excluded from the study. FDCs were analysed for the different pattern of prescribing and rationalism. Results were expressed as percentages. Results: Out of 639 FDCs, the most commonly prescribed FDCs were B complex (12.20%, pantoprazole plus domperidone (9.55% and amoxicillin plus clavulanic acid (7.35%. Seventy percent of the FDCs were prescribed to the age group of 21-60 years. The FDCs were maximum from the department of medicine (25.59%, followed by surgery (15.47% and ENT 13.69%. Out of 278 FDCs, only 5.4% were rational, and rest of the FDCs were irrational. Ninety five percent of all FDCs were brand names. The physicians were unaware of the active pharmacological ingredients (APIs of 20.86% FDCs. Ninety two percent FDCs were available as over the counter (OTCs. Forty eight percent FDCs were costing from Rs. 0-50. There were 2.87% FDCs whose price was above Rs. 500. Conclusions: Irrational FDCs are prescribed by all the departments. Physicians were ignorant about the essential drugs and FDCs. Patients didn’t have access to rational medicines. Therefore, physicians and regulators should be alerted in time. Regulatory actions or government laws should be made mandatory. Availability and access to 348 essential medicines for basic health care should be the priority of the

  5. Combined phylogeny and neighborhood analysis of the evolution of the ABC transporters conferring multiple drug resistance in hemiascomycete yeasts

    Directory of Open Access Journals (Sweden)

    Goffeau André

    2009-10-01

    Full Text Available Abstract Background Pleiotropic Drug Resistant transporters (PDR are members of the ATP-Binding Cassette (ABC subfamily which export antifungals and other xenobiotics in fungi and plants. This subfamily of transmembrane transporters has nine known members in Saccharomyces cerevisiae. We have analyzed the complex evolution of the pleiotropic drug resistance proteins (Pdrp subfamily where gene duplications and deletions occur independently in individual genomes. This study was carried out on 62 Pdrp from nine hemiascomycetous species, seven of which span 6 of the 14 clades of the Saccharomyces complex while the two others species, Debaryomyces hansenii and Yarrowia lipolytica, are further apart from an evolutive point of view. Results Combined phylogenetic and neighborhood analyses enabled us to identify five Pdrp clusters in the Saccharomyces complex. Three of them comprise orthologs of the Pdrp sensu stricto, Pdr5p, Pdr10p, Pdr12p, Pdr15p, Snq2p and YNR070wp. The evolutive pathway of the orthologs of Snq2 and YNR070w is particularly complex due to a tandem gene array in Eremothecium gossypii, Kluyveromyces lactis and Saccharomyces (Lachancea kluyveri. This pathway and different cases of duplications and deletions were clarified by using a neighborhood analysis based on synteny. For the two distant species, Yarrowia lipolytica and Debaryomyces hansenii, no neighborhood evidence is available for these clusters and many homologs of Pdr5 and Pdr15 are phylogenetically assigned to species-based clusters. Two other clusters comprise the orthologs of the sensu lato Pdrp, Aus1p/Pdr11p and YOL075cp respectively. The evolutionary pathway of these clusters is simpler. Nevertheless, orthologs of these genes are missing in some species. Conclusion Numerous duplications were traced among the Hemiascomycetous Pdrp studied. The role of the Whole Genome Duplication (WGD is sorted out and our analyses confirm the common ancestrality of Pdr5p and Pdr15p. A tandem

  6. The application of high-resolution mass spectrometry-based data-mining tools in tandem to metabolite profiling of a triple drug combination in humans.

    Science.gov (United States)

    Xing, Jie; Zang, Meitong; Zhang, Haiying; Zhu, Mingshe

    2015-10-15

    Patients are usually exposed to multiple drugs, and metabolite profiling of each drug in complex biological matrices is a big challenge. This study presented a new application of an improved high resolution mass spectrometry (HRMS)-based data-mining tools in tandem to fast and comprehensive metabolite identification of combination drugs in human. The model drug combination was metronidazole-pantoprazole-clarithromycin (MET-PAN-CLAR), which is widely used in clinic to treat ulcers caused by Helicobacter pylori. First, mass defect filter (MDF), as a targeted data processing tool, was able to recover all relevant metabolites of MET-PAN-CLAR in human plasma and urine from the full-scan MS dataset when appropriate MDF templates for each drug were defined. Second, the accurate mass-based background subtraction (BS), as an untargeted data-mining tool, worked effectively except for several trace metabolites, which were buried in the remaining background signals. Third, an integrated strategy, i.e., untargeted BS followed by improved MDF, was effective for metabolite identification of MET-PAN-CLAR. Most metabolites except for trace ones were found in the first step of BS-processed datasets, and the results led to the setup of appropriate metabolite MDF template for the subsequent MDF data processing. Trace metabolites were further recovered by MDF, which used both common MDF templates and the novel metabolite-based MDF templates. As a result, a total of 44 metabolites or related components were found for MET-PAN-CLAR in human plasma and urine using the integrated strategy. New metabolic pathways such as N-glucuronidation of PAN and dehydrogenation of CLAR were found. This study demonstrated that the combination of accurate mass-based multiple data-mining techniques in tandem, i.e., untargeted background subtraction followed by targeted mass defect filtering, can be a valuable tool for rapid metabolite profiling of combination drugs in vivo. PMID:26515003

  7. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    International Nuclear Information System (INIS)

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  8. Chemical interactions study of antiretroviral drugs efavirenz and lamivudine concerning the development of stable fixed-dose combination formulations for AIDS treatment

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Elionai C. de L.; Mussel, Wagner N.; Resende, Jarbas M.; Yoshida, Maria I., E-mail: mirene@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Fialho, Silvia L.; Barbosa, Jamile; Fialho, Silvia L. [Fundacao Ezequiel Dias, Belo Horizonte, MG (Brazil)

    2013-04-15

    Lamivudine and efavirenz are among the most worldwide used drugs for acquired immune deficiency syndrome (AIDS) treatment. Solid state nuclear magnetic resonance (ssNMR), Fourier-transformed infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermo-optical analysis (TOA) were used to study possible interactions between these drugs, aiming the development of a fixed-dose drug combination. DSC and TOA have evidenced significant shifts on the melting points of both drugs in the mixture, which may be due to interaction between them. Although DSC and TOA results indicated incompatibility between the drugs, FTIR spectra were mostly unmodified due to overlapping peaks. The ssNMR analyses showed significant changes in chemical shifts values of the mixture when compared with spectra of pure drugs, especially in the signals relating to the deficient electron carbon atoms of both drugs. These results confirm the interactions suggested by DSC and TOA, which is probably due to acid-base interactions between electronegative and deficient electron atoms of both lamivudine and efavirenz. (author)

  9. Evaluation of Atazanavir and Darunavir Interactions with Lipids for Developing pH-responsive Anti-HIV Drug Combination Nanoparticles

    OpenAIRE

    Duan, Jinghua; Freeling, Jennifer P.; Koehn, Josefin; Shu, Cuiling; Ho, Rodney J. Y.

    2014-01-01

    We evaluated two HIV protease inhibitors, atazanavir and darunavir, for pH-dependent solubility, lipid binding, and drug release from lipid nanoparticles. Both atazanavir and darunavir incorporated into lipid nanoparticles composed of pegylated and non-pegylated phospholipids with nearly 100% efficiency, but only atazanavir lipid nanoparticles formed stable lipid-drug particles and exhibited pH-dependent drug release. Darunavir lipid nanoparticles were unstable and formed mixed micelles at lo...

  10. A two-phase model for drug release from microparticles with combined effects of solubilisation and recrystallisation.

    Science.gov (United States)

    Chakravarty, Koyel; Dalal, D C

    2016-02-01

    The present study aims to provide a comprehensive mathematical model for drug release from microparticles to the adjacent tissues. In the elucidation of drug release mechanisms, the role of mathematical modelling has been depicted thereby facilitating the development of new therapeutic drug by a systematic approach, rather than expensive experimental trial-and-error methods. In order to study the whole process, a two-phase mathematical model describing the dynamics of drug transport in two coupled media is presented. Drug release is described taking into consideration both solubilisation dynamics of drug crystallites and diffusion of the solubilised drug through the microparticle. In the coupled media, reversible dissociation/recystallisation processes are taking place. The model has led to a system of partial differential equations that are solved analytically. The model points out the important roles played by the diffusion, mass-transfer and reaction parameters, which are the main architects behind drug kinetics across two layers. The dependence of drug masses on the main parameters is also analysed. PMID:26631511

  11. INTUBATIONS CONDITIONS AND HOMODYNAMIC RESPONSES UNDER ANESTHESIA INDUCTION WITH THREE COMBINATION DRUGS: ALFENTANIL- MIDAZOLAM, ALFENTANIL- THIOPENTAL AND ALFENTANIL- KETAMINE

    Directory of Open Access Journals (Sweden)

    H SOLTANI NEZHAD

    2000-03-01

    Full Text Available Background. Administration of alfentanil followed by propofol intravenously (IV without neuromuscular blockage for induction of anesthesia provides adaquate conditions for tracheal intubation. Other hypnotic drugs have not been thoroughly investigated in this regard. The aim of the present study was comparison of intubation conditions and hemodynamic responses of anesthesia induction with alfentanil/midazolam, alfentanil/Na thiopental and alfentanil/ ketamine. Methods. In a clinical trial study one hundred and twenty children were randomly allocated to four groups. Medication in these groups were alfentanil 40 µg/kg+ midazolam 200 µg/kg,alfentanil 40 µg/kg+Na thiopental 6 µg/kg, alfentanil 40 µg/kg+ketamin 2 mg/kg & Na thipental 6 mg/kg+suxamethonium 2 mg/kg (as control group. In all patients the ease of ventilation via face mask, jaw mobility, degree of exposure and position of vocal cords, patient's response to tracheal intubation, duration of time was needed for intubation and hemodynamic changes after intubation were assessed and recorded. Findings. There are significant differences between first three groups (interventional groups for jaw mebility, ventilation, vocal cord visuality, vocal cord position, patient movement during laryngoscopy and mean laryngoscopy time, (P < 0.05. There is significant difference between all groups of nesdonal+alfentanil except for patient movement. There is significant difference between mean SBP and PR before and after intubation in first and third group. Conclusion. Results represent that the group of Alfentanil plus Nesdonal had a better quality of ventilation rather than two other groups. It is recommended that administration of alfentanil plus thiopental combination is preferred in cases that using muscle relaxant is contraindicated.

  12. Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering.

    Science.gov (United States)

    Yan, Jingxuan; Miao, Yuting; Tan, Huaping; Zhou, Tianle; Ling, Zhonghua; Chen, Yong; Xing, Xiaodong; Hu, Xiaohong

    2016-06-01

    Injectable and biodegradable alginate-based composite gel scaffolds doubly integrated with hydroxyapatite (HAp) and gelatin microspheres (GMs) were cross-linked via in situ release of calcium cations. As triggers of calcium cations, CaCO3 and glucono-d-lactone (GDL) were fixed as a mass ratio of 1:1 to control pH value ranging from 6.8 to 7.2 during gelation. Synchronously, tetracycline hydrochloride (TH) was encapsulated into GMs to enhance bioactivity of composite gel scaffolds. The effects of HAp and GMs on characteristics of gel scaffolds, including pH value, gelation time, mechanical properties, swelling ratio, degradation behavior and drug release, were investigated. The results showed that HAp and GMs successfully improved mechanical properties of gel scaffolds at strain from 0.1 to 0.5, which stabilized the gel network and decreased weight loss, as well as swelling ratio and gelation time. TH could be released from this composite gel scaffold into the local microenvironment in a controlled fashion by the organic/inorganic hybrid of hydrogel network. Our results demonstrate that the HAp and GMs doubly integrated alginate-based gel scaffolds, especially the one with 6% (w/v) HAp and 5% (w/v) GMs, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for bone tissue engineering. The potential application of this gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. In combination with TH, the gel scaffold exhibited beneficial effects on osteoblast activity, which suggested a promising future for local treatment of pathologies involving bone loss. PMID:27040220

  13. Artemisinin combination therapies price disparity between government and private health sectors and its implication on antimalarial drug consumption pattern in Morogoro Urban District, Tanzania

    Directory of Open Access Journals (Sweden)

    Malisa Allen

    2012-03-01

    Full Text Available Abstract Background Universal access to effective treatments is a goal of the Roll Back Malaria Partnership. However, despite official commitments and substantial increases in financing, this objective remains elusive, as development assistance continue to be routed largely through government channels, leaving the much needed highly effective treatments inaccessible or unaffordable to those seeking services in the private sector. Methods To quantify the effect of price disparity between the government and private health systems, this study have audited 92 government and private Drug Selling Units (DSUs in Morogoro urban district in Tanzania to determine the levels, trend and consumption pattern of antimalarial drugs in the two health systems. A combination of observation, interviews and questionnaire administered to the service providers of the randomly selected DSUs were used to collect data. Results ALU was the most selling antimalarial drug in the government health system at a subsidized price of 300 TShs (0.18 US$. By contrast, ALU that was available in the private sector (coartem was being sold at a price of about 10,000 TShs (5.9 US$, the price that was by far unaffordable, prompting people to resort to cheap but failed drugs. As a result, metakelfin (the phased out drug was the most selling drug in the private health system at a price ranging from 500 to 2,000 TShs (0.29–1.18 US$. Conclusions In order for the prompt diagnosis and treatment with effective drugs intervention to have big impact on malaria in mostly low socioeconomic malaria-endemic areas of Africa, inequities in affordability and access to effective treatment must be eliminated. For this to be ensued, subsidized drugs should be made available in both government and private health sectors to promote a universal access to effective safe and affordable life saving antimalarial drugs.

  14. Evaluation of Drug-Drug Interactions between Direct-Acting Anti-Hepatitis C Virus Combination Regimens and the HIV-1 Antiretroviral Agents Raltegravir, Tenofovir, Emtricitabine, Efavirenz, and Rilpivirine.

    Science.gov (United States)

    Khatri, Amit; Dutta, Sandeep; Dunbar, Martin; Podsadecki, Thomas; Trinh, Roger; Awni, Walid; Menon, Rajeev

    2016-05-01

    The three direct-acting antiviral agent (3D) regimen is a novel combination of direct-acting antiviral agents (DAAs) that has proven effective for the treatment of hepatitis C virus (HCV) infection. Given the potential for coadministration in patients with human immunodeficiency virus infection, possible drug interactions with antiretroviral drugs must be carefully considered. Four phase 1, multiple-dose pharmacokinetic studies were conducted in healthy volunteers (n = 66). The 3D regimen of 150/100 mg daily paritaprevir/ritonavir, 25 mg daily ombitasvir, and 400 mg twice-daily dasabuvir was administered alone or in combination with 200 mg daily of emtricitabine and 300 mg daily of tenofovir disoproxil fumarate (tenofovir DF), 25 mg daily of rilpivirine, or 400 mg of raltegravir twice daily. A 2-DAA regimen of 150/100 mg daily paritaprevir/ritonavir and 400 mg of dasabuvir twice daily was also studied in combination with efavirenz/emtricitabine/tenofovir DF at 600/200/300 mg daily, respectively (Atripla; Bristol-Myers Squibb). Pharmacokinetic parameters were determined from plasma drug concentrations. No clinically significant drug interactions were observed (≤32% change in exposure) between the 3D regimen and that of emtricitabine plus tenofovir DF. Raltegravir exposure was increased up to 134% when the drug was coadministered with the 3D regimen. Although coadministration with rilpivirine was well tolerated in healthy volunteers, observed elevations in rilpivirine exposures may increase the potential for adverse drug reactions. Concomitant use of the 2-DAA regimen and efavirenz/emtricitabine/tenofovir DF was discontinued owing to poor tolerability and adverse events. No dose adjustment is required during coadministration of raltegravir, tenofovir DF, or emtricitabine with the 3D regimen. Rilpivirine is not recommended and efavirenz is contraindicated for coadministration with the 3D regimen. PMID:26953200

  15. Suppression of postoperative pain by the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine.

    Science.gov (United States)

    Dionne, R A; Wirdzek, P R; Fox, P C; Dubner, R

    1984-04-01

    The analgesic efficacy of the combination of a nonsteroidal anti-inflammatory drug, flurbiprofen, and a long-acting local anesthetic, etidocaine, was evaluated for the suppression of acute postoperative pain. Subjects having two impacted third molars removed at two appointments received either the experimental combination or standard treatment in a randomized, crossover design. The experimental treatment consisted of 100 mg flurbiprofen 30 minutes before surgery, 1.5% etidocaine with 1:200,000 epinephrine five minutes before surgery, and 100 mg flurbiprofen three hours after surgery. Standard treatment consisted of 10 mg oxycodone plus 650 mg acetaminophen 30 minutes before surgery, 2% lidocaine with 1:100,000 epinephrine five minutes before surgery, and a second dose of the oxycodone-acetaminophen combination three hours after surgery. Pain intensity was rated hourly from one to seven hours after surgery, using a variety of ordinal and analog scales. The flurbiprofen-etidocaine combination resulted in significantly less postoperative pain than the oxycodone plus acetaminophen-lidocaine combination on all four analgesic scales used and was preferred by the majority of the patients. This study shows that pretreatment with a nonsteroidal anti-inflammatory drug, flurbiprofen, in combination with a long-acting local analgesic, etidocaine, suppresses pain to a greater extent than a potent opiate mild/analgesic combination and lidocaine without an increase in side-effect liability. PMID:6586802

  16. Quantitative analysis of the anti-proliferative activity of combinations of selected iron-chelating agents and clinically used anti-neoplastic drugs.

    Directory of Open Access Journals (Sweden)

    Eliska Potuckova

    Full Text Available Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, we explored the combined anti-proliferative potential of four iron chelators, namely: desferrioxamine (DFO, salicylaldehyde isonicotinoyl hydrazone (SIH, (E-N'-[1-(2-hydroxy-5-nitrophenylethyliden] isonicotinoyl hydrazone (NHAPI, and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT, plus six selected anti-neoplastic drugs. These six agents are used for breast cancer treatment and include: paclitaxel, 5-fluorouracil, doxorubicin, methotrexate, tamoxifen and 4-hydroperoxycyclophosphamide (an active metabolite of cyclophosphamide. Our quantitative chelator-drug analyses were designed according to the Chou-Talalay method for drug combination assessment. All combinations of these agents yielded concentration-dependent, anti-proliferative effects. The hydrophilic siderophore, DFO, imposed antagonism when used in combination with all six anti-tumor agents and this antagonistic effect increased with increasing dose. Conversely, synergistic interactions were observed with combinations of the lipophilic chelators, NHAPI or Dp44mT, with doxorubicin and also the combinations of SIH, NHAPI or Dp44mT with tamoxifen. The combination of Dp44mT with anti-neoplastic agents was further enhanced following formation of its redox-active iron and especially copper complexes. The most potent combinations of Dp44mT and NHAPI with tamoxifen were confirmed as synergistic using another estrogen receptor-expressing breast cancer cell line, T47D, but not estrogen receptor

  17. Quantitative analysis of the anti-proliferative activity of combinations of selected iron-chelating agents and clinically used anti-neoplastic drugs.

    Science.gov (United States)

    Potuckova, Eliska; Jansova, Hana; Machacek, Miloslav; Vavrova, Anna; Haskova, Pavlina; Tichotova, Lucie; Richardson, Vera; Kalinowski, Danuta S; Richardson, Des R; Simunek, Tomas

    2014-01-01

    Recent studies have demonstrated that several chelators possess marked potential as potent anti-neoplastic drugs and as agents that can ameliorate some of the adverse effects associated with standard chemotherapy. Anti-cancer treatment employs combinations of several drugs that have different mechanisms of action. However, data regarding the potential interactions between iron chelators and established chemotherapeutics are lacking. Using estrogen receptor-positive MCF-7 breast cancer cells, we explored the combined anti-proliferative potential of four iron chelators, namely: desferrioxamine (DFO), salicylaldehyde isonicotinoyl hydrazone (SIH), (E)-N'-[1-(2-hydroxy-5-nitrophenyl)ethyliden] isonicotinoyl hydrazone (NHAPI), and di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), plus six selected anti-neoplastic drugs. These six agents are used for breast cancer treatment and include: paclitaxel, 5-fluorouracil, doxorubicin, methotrexate, tamoxifen and 4-hydroperoxycyclophosphamide (an active metabolite of cyclophosphamide). Our quantitative chelator-drug analyses were designed according to the Chou-Talalay method for drug combination assessment. All combinations of these agents yielded concentration-dependent, anti-proliferative effects. The hydrophilic siderophore, DFO, imposed antagonism when used in combination with all six anti-tumor agents and this antagonistic effect increased with increasing dose. Conversely, synergistic interactions were observed with combinations of the lipophilic chelators, NHAPI or Dp44mT, with doxorubicin and also the combinations of SIH, NHAPI or Dp44mT with tamoxifen. The combination of Dp44mT with anti-neoplastic agents was further enhanced following formation of its redox-active iron and especially copper complexes. The most potent combinations of Dp44mT and NHAPI with tamoxifen were confirmed as synergistic using another estrogen receptor-expressing breast cancer cell line, T47D, but not estrogen receptor-negative MDA

  18. Incorporating Natural Products, Pharmaceutical Drugs, Self-Care and Digital/Mobile Health Technologies into Molecular-Behavioral Combination Therapies for Chronic Diseases.

    Science.gov (United States)

    Bulaj, Grzegorz; Ahern, Margaret M; Kuhn, Alexis; Judkins, Zachary S; Bowen, Randy C; Chen, Yizhe

    2016-01-01

    Merging pharmaceutical and digital (mobile health, mHealth) ingredients to create new therapies for chronic diseases offers unique opportunities for natural products such as omega-3 polyunsaturated fatty acids (n-3 PUFA), curcumin, resveratrol, theanine, or α-lipoic acid. These compounds, when combined with pharmaceutical drugs, show improved efficacy and safety in preclinical and clinical studies of epilepsy, neuropathic pain, osteoarthritis, depression, schizophrenia, diabetes and cancer. Their additional clinical benefits include reducing levels of TNFα and other inflammatory cytokines. We describe how pleiotropic natural products can be developed as bioactive incentives within the network pharmacology together with pharmaceutical drugs and self-care interventions. Since approximately 50% of chronically-ill patients do not take pharmaceutical drugs as prescribed, psychobehavioral incentives may appeal to patients at risk for medication non-adherence. For epilepsy, the incentive-based network therapy comprises anticonvulsant drugs, antiseizure natural products (n-3 PUFA, curcumin or/and resveratrol) coupled with disease-specific behavioral interventions delivered by mobile medical apps. The add-on combination of antiseizure natural products and mHealth supports patient empowerment and intrinsic motivation by having a choice in self-care behaviors. The incentivized therapies offer opportunities: (1) to improve clinical efficacy and safety of existing drugs, (2) to catalyze patient-centered, disease self-management and behavior-changing habits, also improving health-related quality-of-life after reaching remission, and (3) merging copyrighted mHealth software with natural products, thus establishing an intellectual property protection of medical treatments comprising the natural products existing in public domain and currently promoted as dietary supplements. Taken together, clinical research on synergies between existing drugs and pleiotropic natural products

  19. β-Lapachone and Paclitaxel Combination Micelles with Improved Drug Encapsulation and Therapeutic Synergy as Novel Nanotherapeutics for NQO1-Targeted Cancer Therapy.

    Science.gov (United States)

    Zhang, Ling; Chen, Zhen; Yang, Kuan; Liu, Chun; Gao, Jinming; Qian, Feng

    2015-11-01

    β-Lapachone (LPC) is a novel cytotoxic agent that is bioactivated by NADP(H): quinone oxidoreductase 1 (NQO1), an enzyme elevated in a variety of tumors, such as non-small cell lung cancer (NSCLC), pancreatic cancer, liver cancer, and breast cancer. Despite its unique mechanism of action, its clinical evaluation has been largely hindered by low water solubility, short blood half-life, and narrow therapeutic window. Although encapsulation into poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) micelles could modestly improve its solubility and prolong its half-life, the extremely fast intrinsic crystallization tendency of LPC prevents drug loading higher than ∼2 wt %. The physical stability of the LPC-loaded micelles is also far from satisfactory for further development. In this study, we demonstrate that paclitaxel (PTX), a front-line drug for many cancers, can provide two functions when coencapsulated together with LPC in the PEG-PLA micelles; first, as a strong crystallization inhibitor for LPC, thus to significantly increase the LPC encapsulation efficiency in the micelle from 11.7 ± 2.4% to 100.7 ± 2.2%. The total drug loading efficiency of both PTX and LPC in the combination polymeric micelle reached 100.3 ± 3.0%, and the drug loading density reached 33.2 ± 1.0%. Second, the combination of LPC/PTX demonstrates strong synergistic cytotoxicity effect against the NQO1 overexpressing cancer cells, including A549 NSCLC cells, and several pancreatic cancer cells (combination index effect at different cell checkpoints. The PEG-PLA micelles coloaded with LPC and PTX offer a novel nanotherapeutic, with high drug loading, sufficient physical stability, and biological synergy to increase drug delivery efficiency and optimize the therapeutic window for NOQ1-targeted therapy of cancer. PMID:26415823

  20. Investigation of Elimination Rate, Persistent Subpopulation Removal, and Relapse Rates of Mycobacterium tuberculosis by Using Combinations of First-Line Drugs in a Modified Cornell Mouse Model

    Science.gov (United States)

    Pertinez, Henry; Ortega-Muro, Fatima; Alameda-Martin, Laura; Liu, Yingjun; Schipani, Alessandro; Davies, Geraint; Coates, Anthony

    2016-01-01

    Currently, the most effective tuberculosis control method involves case finding and 6 months of chemotherapy. There is a need to improve our understanding about drug interactions, combination activities, and the ability to remove persistent bacteria using the current regimens, particularly in relation to relapse. We aimed to investigate the therapeutic effects of three main components, rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA), in current drug regimens using a modified version of the Cornell mouse model. We evaluated the posttreatment levels of persistent Mycobacterium tuberculosis in the organs of mice using culture filtrate derived from M. tuberculosis strain H37Rv. When RMP was combined with INH, PZA, or INH-PZA, significant additive activities were observed compared to each of the single-drug treatments. However, the combination of INH and PZA showed a less significant additive effect than either of the drugs used on their own. Apparent culture negativity of mouse organs was achieved at 14 weeks of treatment with RMP-INH, RMP-PZA, and RMP-INH-PZA, but not with INH-PZA, when conventional tests, namely, culture on solid agar and in liquid broth, indicated that the organs were negative for bacteria. The relapse rates for RMP-containing regimens were not significantly different from a 100% relapse rate at the numbers of mice examined in this study. In parallel, we examined the organs for the presence of culture filtrate-dependent persistent bacilli after 14 weeks of treatment. Culture filtrate treatment of the organs revealed persistent M. tuberculosis. Modeling of mycobacterial elimination rates and evaluation of culture filtrate-dependent organisms showed promise as surrogate methods for efficient factorial evaluation of drug combinations in tuberculosis in mouse models and should be further evaluated against relapse. The presence of culture filtrate-dependent persistent M. tuberculosis is the likely cause of disease relapse in this modified Cornell

  1. Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach.

    Science.gov (United States)

    Xiang, Jinbao; Zhang, Zhuoqi; Mu, Yan; Xu, Xianxiu; Guo, Sigen; Liu, Yongjin; Russo, Daniel P; Zhu, Hao; Yan, Bing; Bai, Xu

    2016-05-01

    An efficient discovery strategy by combining diversity-oriented synthesis and converging cellular screening is described. By a three-round screening process, we identified novel tricyclic pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR (EC50 100 μM against normal human fibroblasts). The most active hits also exhibited drug-like properties suitable for further preclinical research. This redeployment of antidepressing compounds for anticancer applications provides promising future prospects for treating drug-resistant tumors with fewer side effects. PMID:27082930

  2. CLINICAL OBSERVATION ON THE THERAPEUTIC EFFECT OF COMBINED THERAPIES OF ACUPUNCTURE, POINT-INJECTION AND ADMINISTRATION OF CHINESE DRUGS FOR TREATMENT OF 443 CASES OF MENTAL RETARDATION CHILDREN

    Institute of Scientific and Technical Information of China (English)

    袁青; 靳瑞; 张洪来; 邓倩平

    2000-01-01

    Mental retardation (MR) children are referred to those who have a lower intelligence incomparison with that of the normal children with similar ages in the developmenal stage and someconcurrent defects in adaptive behavior simultaneously. In the past more than 10 years, we adopted “Jinsanzhen ( Jin'' s Three Needles )”principally to treat many MR children and achieved satisfied results[1,2]. In Order to rais ethe therapeutic effect further, we adopted combined therapies of “Jin-three Needles” and pointinjection of drugs and oral administration of Chinese patent drugs to treat it and obtained a striking therapeutic effect. Here is the report.

  3. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

    Directory of Open Access Journals (Sweden)

    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  4. The effect of exercise combined with Chinese drugs on hypertension%运动疗法配合中药治疗高血压病

    Institute of Scientific and Technical Information of China (English)

    冯志宏

    2001-01-01

    @@Background:Drug therapy of hypertension is common in clinic.But hypertension will reocur when drug treatment is arrested.Hypertension belongs to headache and dizziness in chinese medicine.The liver-gas,stagnated fire,fire-transmission,deficiency of the kidney-yin,hyperactivity of the liver-yang may contributed to its development. Objective:To treat hypertension with exercise combined with drugs. Design:173 patients with hypertension were randomly divided into two groups,treatment group and control group.Patients in treatment group recepted exercise therapy,for patients with severe hypertension,Xaiozhiyin was administered.Patients in control group recepted oral Xiaozhiyin.Unit:Hangzhou Tianmushan Pharmacy Company,Hangzhou

  5. Accelerated killing of cancer cells using a multifunctional single-walled carbon nanotube-based system for targeted drug delivery in combination with photothermal therapy

    Directory of Open Access Journals (Sweden)

    Jeyamohan P

    2013-07-01

    Full Text Available Prashanti Jeyamohan, Takashi Hasumura, Yutaka Nagaoka, Yasuhiko Yoshida, Toru Maekawa, D Sakthi Kumar Bio-Nano Electronics Research Centre, Graduate School of Interdisciplinary New Science, Toyo University, Kawagoe, Japan Abstract: The photothermal effect of single-walled carbon nanotubes (SWCNTs in combination with the anticancer drug doxorubicin (DOX for targeting and accelerated destruction of breast cancer cells is demonstrated in this paper. A targeted drug-delivery system was developed for selective killing of breast cancer cells with polyethylene glycol biofunctionalized and DOX-loaded SWCNTs conjugated with folic acid. In our work, in vitro drug-release studies showed that the drug (DOX binds at physiological pH (pH 7.4 and is released only at a lower pH, ie, lysosomal pH (pH 4.0, which is the characteristic pH of the tumor environment. A sustained release of DOX from the SWCNTs was observed for a period of 3 days. SWCNTs have strong optical absorbance in the near-infrared (NIR region. In this special spectral window, biological systems are highly transparent. Our study reports that under laser irradiation at 800 nm, SWCNTs exhibited strong light–heat transfer characteristics. These optical properties of SWCNTs open the way for selective photothermal ablation in cancer therapy. It was also observed that internalization and uptake of folate-conjugated NTs into cancer cells was achieved by a receptor-mediated endocytosis mechanism. Results of the in vitro experiments show that laser was effective in destroying the cancer cells, while sparing the normal cells. When the above laser effect was combined with DOX-conjugated SWCNTs, we found enhanced and accelerated killing of breast cancer cells. Thus, this nanodrug-delivery system, consisting of laser, drug, and SWCNTs, looks to be a promising selective modality with high treatment efficacy and low side effects for cancer therapy. Keywords: cancer, nanotherapy, SWCNTs, targeted drug delivery

  6. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura;

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...... with detection of TDR, with virological (viral load<500 copies/mL) and CD4 count response (>or=50% increase) to combination antiretroviral therapy at months 6-12. RESULTS: The overall prevalence of TDR was 11.4%, which was stable over 1996-2004. There were no significant differences in virological...... suppression (those resistant to at least one drug prescribed versus susceptible), adjusted odds ratio: 0.68 (95% confidence interval: 0.27 to 1.71; P=0.408) or CD4 count response, adjusted odds ratio: 1.65 (95% confidence interval: 0.73 to 3.73; P=0.231). CONCLUSIONS: Prevalence of TDR in antiretroviral...

  7. Treatment of Severe Aplastic Anemia by Immunosuppressor Anti-lymphocyte Globulin/Anti-thymus Globulin as the Chief Medicine in Combination with Chinese Drugs

    Institute of Scientific and Technical Information of China (English)

    郑兵荣; 沈建平; 庄海峰; 林圣云; 沈一平; 周郁鸿

    2009-01-01

    Objective:To study the therapeutic effect of combined therapy with Chinese drugs and immunosuppressors, mainly anti-lymphocyte globulin/anti-thymus globulin(ALG/ATG),for the treatment of severe aplastic anemia(SAA),the efficacy associated factors and adverse effects as well.Methods:A retrospective analysis was conducted on 65 patients with SAA treated by combined therapy which was supplemented with cyclosporin A,androgen,hematopoietic growth factor,etc.Results:Of the 57 patients followed-up,26 (45.6%) we...

  8. The efficacy and tolerability of the slow-acting combined agent glucosamine and chondroitin sulfate in gonarthrosis patients tacking no nonsteroidal anti-inflammatory drugs

    OpenAIRE

    A P Rebrov; Romanova, I.A.; I. Z. Gaydukova

    2015-01-01

    Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs).Patients and methods. The investigation enrolled 84 patients (78 women and 6 men) aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg) with or without...

  9. Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timori and of intestinal helminths on Alor Island, Indonesia

    OpenAIRE

    Oqueka, Tim; Supali, Taniawati; Ismid, Is Suhariah; Purnomo,; Rückert, Paul; Bradley, Mark; Fischer, Peter

    2005-01-01

    Background Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking. Methods The effect of one selective treatment and two rounds of MDA using DEC and alb on th...

  10. Oral Administration and External Application of Chinese Drugs Combined with Micro-invasive Operation for the Treatment of Varicose Ulcers in the Lower Extremities

    Institute of Scientific and Technical Information of China (English)

    王小平; 张宇; 粟文娟; 王珊珊; 王英

    2009-01-01

    Objective:To evaluate the clinical therapeutic effects of oral administration and external application of Chinese drugs combined with micro-invasive surgery for the treatment of varicose ulcers in the lower extremities(ecthyma).Methods:A total of 152 patients(163 limbs) suffering from varicose ulcers on the lower limbs were assigned to two groups according to the patients' willingness.The 102 cases(109 limbs) in the treatment group underwent the method of endovenous microwave closure of communicating vei...

  11. Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a baseline study in an era of assumed artemisinin combination therapy (ACT)

    OpenAIRE

    Ringsted Frank M; Massawe Isolide S; Lemnge Martha M; Bygbjerg Ib C

    2011-01-01

    Abstract Background Artemether-lumefantrine (ALu) replaced sulphadoxine-pymimethamine (SP) as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT) is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may u...

  12. Doxorubicin loaded dual pH- and thermo-responsive magnetic nanocarrier for combined magnetic hyperthermia and targeted controlled drug delivery applications

    Science.gov (United States)

    Hervault, Aziliz; Dunn, Alexander E.; Lim, May; Boyer, Cyrille; Mott, Derrick; Maenosono, Shinya; Thanh, Nguyen T. K.

    2016-06-01

    Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced features for the targeted delivery of DOX molecules via the combination of magnetic targeting, and dual pH- and thermo-responsive behaviour which offers spatial and temporal control over the release of DOX. The iron oxide cores exhibit a superparamagnetic behaviour with a saturation magnetization around 70 emu g-1. The MNCs contained 8.1 wt% of polymer and exhibit good heating properties in an alternating magnetic field. The drug release experiments confirmed that only a small amount of DOX was released at room temperature and physiological pH, while the highest drug release of 85.2% was obtained after 48 h at acidic tumour pH under hyperthermia conditions (50 °C). The drug release kinetic followed Korsmeyer-Peppas model and displayed Fickian diffusion mechanism. From the results obtained it can be concluded that this smart magnetic nanocarrier is promising for applications in multi-modal cancer therapy, to target and efficiently deliver heat and drug specifically to the tumour.Magnetic nanocarriers have attracted increasing attention for multimodal cancer therapy due to the possibility to deliver heat and drugs locally. The present study reports the development of magnetic nanocomposites (MNCs) made of an iron oxide core and a pH- and thermo-responsive polymer shell, that can be used as both hyperthermic agent and drug carrier. The conjugation of anticancer drug doxorubicin (DOX) to the pH- and thermo-responsive MNCs via acid-cleavable imine linker provides advanced

  13. A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn2+ Arsenal for Combined Treatment of Gene Regulation and Drug Delivery

    Science.gov (United States)

    He, Zhi-Mei; Zhang, Peng-Hui; Li, Xin; Zhang, Jian-Rong; Zhu, Jun-Jie

    2016-01-01

    As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn2+-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regulation and drug delivery in a controlled manner. By means of aptamer-guided targeting and receptor-mediated endocytosis, the probes were specifically internalized into the HeLa cells and trapped in the acidic endo-/lysosomes, where the ZnO QDs as the built-in Zn2+ arsenal were promptly dissolved to offer Zn2+, leading to the activation of DNAzyme to cleave the substrate strands, and subsequent drug release. Meanwhile, as designed, one part of the cleaved substrate, hybridized with the overexpressed miR-21 in the target cells, thereby declining its intracellular level. Taken together, the down-regulation of miR-21 has a synergistic effect with Dox to efficiently eradicate the cancer cells. Thus, the favorable biocompatibility, cancer cell specificity and combined treatment make the probe promising for therapy of multidrug-resistant cancer and in vivo application. PMID:26956167

  14. Production of polymeric micelles by microfluidic technology for combined drug delivery: application to osteogenic differentiation of human periodontal ligament mesenchymal stem cells (hPDLSCs).

    Science.gov (United States)

    Capretto, L; Mazzitelli, S; Colombo, G; Piva, R; Penolazzi, L; Vecchiatini, R; Zhang, X; Nastruzzi, C

    2013-01-20

    The current paper reports the production of polymeric micelles (PMs), based on pluronic block-copolymers, as drug carriers, precisely controlling the cellular delivery of drugs with various physico-chemical characteristics. PMs were produced with a microfluidic platform to exploit further control on the size characteristic of the PMs. PMs were designed for the co-delivery of dexamethasone (Dex) and ascorbyl-palmitate (AP) to in vitro cultured human periodontal ligament mesenchymal stem cells (hPDLSCs) for the combined induction of osteogenic differentiation. Mixtures of block-copolymers and drugs in organic, water miscible solvent, were conveniently converted in PMs within microfluidic channel leveraging the fast mixing at the microscale. Our results demonstrated that the drugs can be efficiently co-encapsulated in PMs and that different production parameters can be adjusted in order to modulate the PM characteristics. The comparative analysis of PM produced by microfluidic and conventional procedures confirmed that the use of microfluidics platforms allowed the production of PMs in a robust manner with improved controllability, reproducibility, smaller size and polydispersity. Finally, the analysis of the effect of PMs, containing Dex and AP, on the osteogenic differentiation of hPDLSCs is reported. The data demonstrated the effectiveness and safety of PM treatment on hPDLSC. In conclusion, this report indicates that microfluidic approach represents an innovative and useful method for PM controlled preparation, warrant further evaluation as general methodology for the production of colloidal systems for the simultaneous drug delivery. PMID:22884778

  15. Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway.

    Science.gov (United States)

    Mustafa, Gulam; Alrohaimi, Abdulmohsen H; Bhatnagar, Aseem; Baboota, Sanjula; Ali, Javed; Ahuja, Alka

    2016-01-01

    The effectiveness of intranasal drug delivery for brain targeting has emerged as a hope of remedy for various CNS disorders. The nose to brain absorption of therapeutic molecules claims two effective pathways, which include trans-neuronal for immediate action and para-neuronal for delayed action. To evaluate the contribution of both the pathways in absorption of therapeutic molecules and nanocarriers, lidocaine, a nerve-blocking agent, was used to impair the action potential of olfactory nerve. An anti-Parkinson drug ropinirole was covalently complexes with (99m)Tc in presence of SnCl2 using in-house developed reduction technology. The radiolabeled formulations were administered intranasally in lidocaine challenged rabbit and rat. The qualitative and quantitative outcomes of neural and non-neural pathways were estimated using gamma scintigraphy and UHPLC-MS/MS, respectively. The results showed a significant (p ≤ 0.005) increase in radioactivity counts and drug concentration in the brain of rabbit and rat compared to the animal groups challenged with lidocaine. This concludes the significant contribution (p ≤ 0.005) of trans-neuronal and para-neuronal pathway in nose to brain drug delivery. Therefore, results proved that it is an art of a formulator scientist to make the drug carriers to exploit the choice of absorption pathway for their instant and extent of action. PMID:24959938

  16. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono District, Uganda.

    Science.gov (United States)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

    2013-03-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how much customers would be willing to pay for an RDT if offered in these settings. We conducted a contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP) for an RDT and a course of artemisinin-based combination therapy (ACT) with and without RDT confirmation. Factors associated with WTP were investigated using linear regression. The geometric mean WTP for an RDT was US$0.53, US$1.82 for a course of ACT and US$2.05 for a course of ACT after a positive RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings further suggest that the WTP for an RDT and a course of ACT among drug shop customers is considerably lower than prevailing and estimated end-user prices for these commodities. Increasing the uptake of ACTs in drug shops and restricting the sale of ACTs to parasitologically confirmed malaria will therefore require additional measures. PMID:22589226

  17. Ion-exchange solid-phase extraction combined with liquid chromatography-tandem mass spectrometry for the determination of veterinary drugs in organic fertilizers.

    Science.gov (United States)

    Zhao, Zhiyong; Zhang, Yanmei; Xuan, Yanfang; Song, Wei; Si, Wenshuai; Zhao, Zhihui; Rao, Qinxiong

    2016-06-01

    The analysis of veterinary drugs in organic fertilizers is crucial for an assessment of potential risks to soil microbial communities and human health. We develop a robust and sensitive method to quantitatively determine 19 veterinary drugs (amantadine, sulfonamides and fluoroquinolones) in organic fertilizers. The method involved a simple solid-liquid extraction step using the combination of acetonitrile and McIlvaine buffer as extraction solvent, followed by cleanup with a solid-phase extraction cartridge containing polymeric mixed-mode anion-exchange sorbents. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to separate and detect target analytes. We particularly focused on the optimization of sample clean-up step: different diluents and dilution factors were tested. The developed method was validated in terms of linearity, recovery, precision, sensitivity and specificity. The recoveries of all the drugs ranged from 70.9% to 112.7% at three concentration levels, with the intra-day and inter-day relative standard deviation lower than 15.7%. The limits of quantification were between 1.0 and 10.0μg/kg for all the drugs. Matrix effect was minimized by matrix-matched calibration curves. The analytical method was successfully applied for the survey of veterinary drugs contamination in 20 compost samples. The results indicated that fluoroquinolones had higher incidence rate and mean concentration levels ranging from 31.9 to 308.7μg/kg compared with other drugs. We expect the method will provide the basis for risk assessment of veterinary drugs in organic fertilizers. PMID:27131104

  18. A combined experimental and computational study of novel nanocage-based metal-organic frameworks for drug delivery.

    Science.gov (United States)

    Liu, Jian-Qiang; Li, Xue-Feng; Gu, Chu-Ying; da Silva, Júlio C S; Barros, Amanda L; Alves-Jr, Severino; Li, Bao-Hong; Ren, Fei; Batten, Stuart R; Soares, Thereza A

    2015-11-28

    Three new metal organic frameworks (MOFs) with chemical formulae [(CH3)2NH2] [Sm3(L1)2(HCOO)2(DMF)2(H2O)]·2DMF·18H2O (1), [Cu2(L2)(H2O)2]·2.22DMA (2) and [Zn2(L1)(DMA)]·1.75DMA were synthesized and structurally characterized. 1 and 2 show a classical NbO-like topology and have two types of interconnected cages. 3 exhibits an uncommon zzz topology and has two types of interconnected cages. These MOFs can adsorb large amounts of the drug 5-fluorouracil (5-FU) and release it in a progressive way. 5-FU was incorporated into desolvated 1, 2 and 3 with loadings of 0.40, 0.42, and 0.45 g g(-1), respectively. The drug release rates were 72%, 96% and 79% of the drug after 96 hours in 1, 120 hours in 2 and 96 hours in 3, respectively. Grand Canonical Monte Carlo (GCMC) simulations were performed to investigate the molecular interactions during 5-FU adsorption to the three novel materials. The GCMC simulations reproduced the experimental trend with respect to the drug loading capacity of each material. They also provided a structural description of drug packing within the frameworks, helping to explain the load capacity and controlled release characteristics of the materials. 5-FU binding preferences to 1, 2 and 3 reflect the diversity in pore types, chemistry and sizes. The calculated drug load is more related to the molecular properties of accessible volume Vacc than to the pore size. PMID:26501793

  19. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees

    OpenAIRE

    Guseman, Alex J.; Kaliah Miller; Grace Kunkle; Dively, Galen P.; Jeffrey S Pettis; Evans, Jay D.; Dennis vanEngelsdorp; Hawthorne, David J.

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporte...

  20. Combination strategy of multi-layered surface camouflage using hyperbranched polyethylene glycol and immunosuppressive drugs for the prevention of immune reactions against transplanted porcine islets.

    Science.gov (United States)

    Haque, Muhammad R; Jeong, Jee-Heon; Byun, Youngro

    2016-04-01

    This study suggests a novel method of stabilizing fragile porcine islets to prevent the dissociation after isolation and reducing immune cell invasion in a combination therapy of 'surface camouflaging' and immunosuppressive drugs (FK506, Rapamycin, MR-1, anti-CD19 mAb, and Clodrosome(®)) to effectively alleviate overall immune reactions against xenotransplanted porcine islets. The surface camouflage of pancreatic islets using biocompatible materials improved stabilization of pancreatic islet and prevented the infiltration of immune cells. Firstly, the surface of porcine islets was camouflaged by SH-6-arm-PEG-lipid and gelatin-catechol (artificial extracellular matrix) in order to stabilize the fragile isolated islets. Secondly, three different PEG layers (6-arm-PEG-SH, 6-arm-PEG-catechol, and linear PEG-SH) were chemically conjugated onto the surface of the stabilized porcine islets. Both artificial extracellular matrix (artificial ECM) and PEGylation effectively covered the surface of porcine islets without increasing the size of the whole islet. In addition, the viability and functionality of the islets were not affected by this multi-layer surface modification. The multi-layer modification significantly reduced the attachment of human serum albumin, fibronectin, and immunoglobulin G in comparison to the control collagen surface. The combination effect of multi-layer PEGylation and cocktailed immunosuppressive drugs on the survival time of the transplanted islets was assessed in a xenogeneic porcine-to-mouse model. The median survival time (MST) of 'artificial ECM + PEGylation' group was 4-fold increased compared to that of control group. In addition, the MST of 'artificial ECM + PEGylation + drug' group was 2.16-fold increased, compared to the 'control + drug' group. In conclusion, we proposed a novel porcine islet transplantation protocol using surface multi-layer modification and cocktailed immunosuppressive drugs, for stabilization and

  1. Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a baseline study in an era of assumed artemisinin combination therapy (ACT

    Directory of Open Access Journals (Sweden)

    Ringsted Frank M

    2011-08-01

    Full Text Available Abstract Background Artemether-lumefantrine (ALu replaced sulphadoxine-pymimethamine (SP as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results All surveyed drug shops illicitly sold SP and quinine (QN, and legally amodiaquine (AQ. Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%, QN (11% and ACT (2%. Conclusions In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp

  2. Cell-penetrating peptide and antibiotic combination therapy: a potential alternative to combat drug resistance in methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Randhawa, Harmandeep Kaur; Gautam, Ankur; Sharma, Minakshi; Bhatia, Rakesh; Varshney, Grish C; Raghava, Gajendra Pal Singh; Nandanwar, Hemraj

    2016-05-01

    The diverse pattern of resistance by methicillin-resistant Staphylococcus aureus (MRSA) is the major obstacle in the treatment of its infections. The key reason of resistance is the poor membrane permeability of drug molecules. Over the last decade, cell-penetrating peptides (CPPs) have emerged as efficient drug delivery vehicles and have been exploited to improve the intracellular delivery of numerous therapeutic molecules in preclinical studies. Therefore, to overcome the drug resistance, we have investigated for the first time the effects of two CPPs (P3 and P8) in combination with four antibiotics (viz. oxacillin, erythromycin, norfloxacin, and vancomycin) against MRSA strains. We found that both CPPs internalized into the MRSA efficiently at very low concentration (oxacillin, norfloxacin, and vancomycin to susceptible levels (generally <1 μg/mL) for almost all five clinical isolates. Further, the bacterial cell death was confirmed by scanning electron microscopy as well as propidium iodide uptake assay. Simultaneously, time-kill kinetics revealed the increased uptake of antibiotics. In summary, CPPs assist to restore the effectiveness of antibiotics at much lower concentration, eliminate the antibiotic toxicity, and represent the CPP-antibiotic combination therapy as a potential novel weapon to combat MRSA infections. PMID:26837216

  3. Regional Lymphotropic Therapy in Combination with Low Level Laser Therapy for Treating Multi-Drug-Resistant Tuberculosis

    Directory of Open Access Journals (Sweden)

    Oksana Dogorova

    2016-03-01

    Full Text Available With the growing incidence of Multi-Drug-Resistant Tuberculosis (MDR-TB in newly identified patients, novel multimodality treatment methods are needed, aimed at reducing the time to sputum conversion and cavity healing, which would be applicable in MDR cases. Our experimental treatment consisted of the following: 1 chemotherapy based on the drug sensitivity profile, 2 local laser irradiation therapy for 25 days, and lymphotropic administration of isoniazid (to subcutaneous tissue in alternating locations: underarm area; fifth intercostal space along the sterna border; subclavian area where the first rib meets the sternum in a daily dose of 10mg/kg 5 times a week. This treatment was significantly more effective in newly detected destructive MDR-TB versus the standard Category IV regimen for MDR-TB in terms of reduced time for sputum culture conversion and cavity healing, estimated to be 6 months after initiation of treatment.

  4. Recent development of single preparations and fixed-dose combination tablets for the treatment of non-insulin-dependent diabetes mellitus : A comprehensive summary for antidiabetic drugs.

    Science.gov (United States)

    Li, Jianwen; Lian, He

    2016-06-01

    As a complex endocrine and metabolic disorder, type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM) has become a major threat to human health. Because of the heterogeneous and progressive disorders induced by insulin resistance and pancreatic b-cell dysfunction, the treatment of NIDDM is still challenging. Although antidiabetic drugs with different pharmacological mechanisms of action have been used clinically, different degrees of undesirable glucose control and the incidences of a variety of side effects, including hypoglycemia, cardiovascular complications and weight gain require the better treatment options. This article has overviewed the current literature about commercially available antidiabetic drugs with different pharmacological mechanisms of action in the treatment of NIDDM, and summarized the published data regarding the efficacy, tolerability, and safety of currently available single preparations and fixed-dose combinations, aiming to provide important information for the development and application of antidiabetic drugs in the future. The literature search from 1989 to 2015 was conducted by PubMed, ScienceDirect, Springer, American Diabetes Association, and U.S. FDA Drugs databases. PMID:27230777

  5. Biochemical, computer, and spectroscopic techniques applied to the study of prions and of combinations of antineoplastic drugs

    OpenAIRE

    Perra, Daniela

    2015-01-01

    This thesis collects the work I have done during the three-year PhD Course. The results obtained are divided according to the research topics addressed: · Drug discovery of anticancer agents and development of synergistic associations (Part I); · Studies on the prion structure and the pathogenesis of prion diseases (Part II). Studies referring to the Part I have been carried out at the University of Cagliari and were focalized on the evaluation and experimental validation of th...

  6. Combining targeted drugs to overcome and prevent resistance of solid cancers with some stem-like cell features

    OpenAIRE

    Jokinen, Elina; Laurila, Niina; Koivunen, Peppi; Koivunen, Jussi P

    2014-01-01

    Treatment resistance significantly inhibits the efficiency of targeted cancer therapies in drug-sensitive genotypes. In the current work, we studied mechanisms for rapidly occurring, adaptive resistance in targeted therapy-sensitive lung, breast, and melanoma cancer cell lines. The results show that in ALK translocated lung cancer lines H3122 and H2228, cells with cancer stem-like cell features characterized by high expression of cancer stem cell markers and/or in vivo tumorigenesis can media...

  7. Hydrogel-forming microneedles prepared from "super swelling" polymers combined with lyophilised wafers for transdermal drug delivery.

    Directory of Open Access Journals (Sweden)

    Ryan F Donnelly

    Full Text Available We describe, for the first time, hydrogel-forming microneedle arrays prepared from "super swelling" polymeric compositions. We produced a microneedle formulation with enhanced swelling capabilities from aqueous blends containing 20% w/w Gantrez S-97, 7.5% w/w PEG 10,000 and 3% w/w Na2CO3 and utilised a drug reservoir of a lyophilised wafer-like design. These microneedle-lyophilised wafer compositions were robust and effectively penetrated skin, swelling extensively, but being removed intact. In in vitro delivery experiments across excised neonatal porcine skin, approximately 44 mg of the model high dose small molecule drug ibuprofen sodium was delivered in 24 h, equating to 37% of the loading in the lyophilised reservoir. The super swelling microneedles delivered approximately 1.24 mg of the model protein ovalbumin over 24 h, equivalent to a delivery efficiency of approximately 49%. The integrated microneedle-lyophilised wafer delivery system produced a progressive increase in plasma concentrations of ibuprofen sodium in rats over 6 h, with a maximal concentration of approximately 179 µg/ml achieved in this time. The plasma concentration had fallen to 71±6.7 µg/ml by 24 h. Ovalbumin levels peaked in rat plasma after only 1 hour at 42.36±17.01 ng/ml. Ovalbumin plasma levels then remained almost constant up to 6 h, dropping somewhat at 24 h, when 23.61±4.84 ng/ml was detected. This work represents a significant advancement on conventional microneedle systems, which are presently only suitable for bolus delivery of very potent drugs and vaccines. Once fully developed, such technology may greatly expand the range of drugs that can be delivered transdermally, to the benefit of patients and industry. Accordingly, we are currently progressing towards clinical evaluations with a range of candidate molecules.

  8. The Effect of Mutations on Drug Sensitivity and Kinase Activity of Fibroblast Growth Factor Receptors: A Combined Experimental and Theoretical Study

    Directory of Open Access Journals (Sweden)

    Tom D. Bunney

    2015-03-01

    Full Text Available Fibroblast growth factor receptors (FGFRs are recognized therapeutic targets in cancer. We here describe insights underpinning the impact of mutations on FGFR1 and FGFR3 kinase activity and drug efficacy, using a combination of computational calculations and experimental approaches including cellular studies, X-ray crystallography and biophysical and biochemical measurements. Our findings reveal that some of the tested compounds, in particular TKI258, could provide therapeutic opportunity not only for patients with primary alterations in FGFR but also for acquired resistance due to the gatekeeper mutation. The accuracy of the computational methodologies applied here shows a potential for their wider application in studies of drug binding and in assessments of functional and mechanistic impacts of mutations, thus assisting efforts in precision medicine.

  9. The impacts of pharmaceutical drugs under ocean acidification: New data on single and combined long-term effects of carbamazepine on Scrobicularia plana.

    Science.gov (United States)

    Freitas, Rosa; Almeida, Ângela; Calisto, Vânia; Velez, Cátia; Moreira, Anthony; Schneider, Rudolf J; Esteves, Valdemar I; Wrona, Frederick J; Figueira, Etelvina; Soares, Amadeu M V M

    2016-01-15

    Ocean acidification and increasing discharges of pharmaceutical contaminants into aquatic systems are among key and/or emerging drivers of environmental change affecting marine ecosystems. A growing body of evidence demonstrates that ocean acidification can have direct and indirect impacts on marine organisms although combined effects with other stressors, namely with pharmaceuticals, have received very little attention to date. The present study aimed to evaluate the impacts of the pharmaceutical drug Carbamazepine and pH 7.1, acting alone and in combination, on the clam Scrobicularia plana. For this, a long-term exposure (28 days)was conducted and a set of oxidative stress markers was investigated. The results obtained showed that S. plana was able to develop mechanisms to prevent oxidative damage when under low pH for a long period, presenting higher survival when exposed to this stressor compared to CBZ or the combination of CBZ with pH 7.1. Furthermore, the toxicity of CBZ on S. plana was synergistically increased under ocean acidification conditions (CBZ + pH 7.1): specimens survival was reduced and oxidative stress was enhanced when compared to single exposures. These findings add to the growing body of evidence that ocean acidification will act to increase the toxicity of CBZ to marine organisms,which has clear implications for coastal benthic ecosystems suffering chronic pollution from pharmaceutical drugs. PMID:26473700

  10. Development and validation of a reversed-phase ultra-performance liquid chromatographic method for the simultaneous determination of six drugs used for combined hypertension therapy.

    Science.gov (United States)

    Kaila, Harshad O; Ambasana, Mrunal A; Shah, Anamik K

    2013-01-01

    A simple, rapid, and reliable ultra-performance LC assay method has been developed for the simultaneous estimation of orally administered hypertension drugs (atenolol, hydrochlorothiazide, amlodipine besylate, indapamide, nifedipine, and lercanidipine hydrochloride), any of which may be administered with atenolol in combined hypertension therapy. Chromatography was carried out at 25 degrees C on a 2.1 x 50 mm id, 1.7 microm particle size Acquity BEH C18 column with the isocratic mobile phase 0.01 M, 4.0 pH aqueous phosphate buffer-acetonitrile (50 + 50, v/v) at a flow rate of 0.35 mL/min. All drugs were separated in less than 4 min with good resolution and minimal tailing, without interference by excipients. The method was validated according to International Conference on Harmonization guidelines, and the acceptance criteria for accuracy, precision, linearity, specificity, and system suitability were met in all cases. The column effluent was monitored at 230 nm. The detector response was linear in the range of 1-20 microg/mL of these drugs. LOD obtained was 0.04 microg/mL for atenolol, 0.02 microg/mL for hydrochlorothiazide, 0.03 microg/mL for amlodipine besylate, 0.03 microg/mL for indapamide, 0.02 microg.mL for nifedipine, and 0.01 microg/mL for lercanidipine hydrochloride. The suggested method has the advantage that all the drugs can be quantified alone or in combination with atenolol using a single mobile phase. PMID:23767353

  11. COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    T. D. Kaplanov

    2015-12-01

    Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

  12. COMPARATIVE ASSESSMENT OF EFFECT OF COMBINED DRUGS OF ACE INHIBITOR AND DIURETIC (“NOLIPREL FORTE” AND “CAPOZIDE” ON CARDIOVASCULAR REMODELING IN HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    T. D. Kaplanov

    2005-01-01

    Full Text Available Aim. To assess antihypertensive efficacy and effect on cardio-vascular remodeling of combined drugs of ACE inhibitor and diuretic, “Noliprel forte” (NF and “Capozide” (CA, in hypertensive high risk patients.Material and methods. 50 hypertensive (II grade patients (25 men and 25 women, 19-65 years old with high cardio-vascular risk took part in comparative opened randomized study. No one of patients received antihypertensive therapy before study. All patients were randomized for therapy with one of combined drug of ACE inhibitors and diuretic. 25 patients took NF (perindopril 4 mg and indapamide 1,25 mg, and 25 patients -CA (captopril 50 mg and hydrochlorothiazide 25 mg. Duration of observation period was 6 months. Before study, after 3 and 6 months of therapy ambulatory blood pressure monitoring (ABPM, echocardiography, cardiac and vessel Dopplerography, ultrasound scanning of general carotid arteries with detection of intima-media thickness (IMT, pulse wave speed (PWS were held in all patients. Blood bio-chemical analysis was done also.Results. After 3 months 2 patients in NF group and 4 ones in CA group were required to reinforce of ther-apy with additional administration of perindoprile 4 mg and captopril 50 mg respectively. As a result of 6-month of therapy in NF group systolic dlood pressure (BP decreased in 14,0% (р<0,001 and diastolic BP – на 12,9% (р<0,001. CA reduced systolic BP by 17,9% (р<0,0001 and diastolic BP – by 17,5% (р<0,001. 76% and 70% of patients in NF and CA groups, respectively, reached target BP level. Positive dynamic of daily profile of BP was observed according to ABPM data. Cerebral blood flow did not worsen despite of BP decrease. Both drugs decreased in thickness of inter-ventricular septum and left ventricular mass. Besides, NF decreased in thickness of left ventricular posterior wall. Both drugs reduced in IMT and decreased in PWS. NF therapy did not change of blood biochemical parameters. CA

  13. Immunotherapy and radiation therapy: considerations for successfully combining radiation into the paradigm of immuno-oncology drug development.

    Science.gov (United States)

    Sharon, Elad; Polley, Mei-Yin; Bernstein, Michael B; Ahmed, Mansoor

    2014-08-01

    As the immunotherapy of cancer comes of age, adding immunotherapeutic agents to radiation therapy has the potential to improve the outcomes for patients with a wide variety of malignancies. Despite the enormous potential of such combination therapy, laboratory data has been lacking and there is little guidance for pursuing novel treatment strategies. Animal models have significant limitation in combining radiation therapy with immunotherapy and some of the limitations of preclinical models are discussed in this article. In addition to the preclinical challenges, radiation therapy and immunotherapy combinations may have overlapping toxicities, and for both types of therapy, early and late manifestations of toxicity are possible. Given these risks, special attention should be given to the design of the specific Phase I clinical trial that is chosen. In this article, we describe several Phase I design possibilities that may be employed, including the 3 + 3 design (also known as the cohort of 3 design), the continual reassessment method (CRM), and the time-to-event continual reassessment method (TITE-CRM). Efficacy end points for further development of combination therapy must be based on multiple factors, including disease type, stage of disease, the setting of therapy and the goal of therapy. While the designs for future clinical trials will vary, it is clear that these two successful modalities of therapy can and should be combined for the benefit of cancer patients. PMID:25003314

  14. Effectiveness of two rounds of mass drug administration using DEC combined with albendazole on the prevalence of Brugia malayi

    OpenAIRE

    Santoso Santoso; Aprioza Yenni; Reni Oktarina; Tri Wurisastuti

    2015-01-01

    Background: Filariasis mass drug administration carried out for 5 consecutive years aims to reduce the prevalence rate of < 1%. Evaluation of treatment needs to be done, one of them with a finger blood survey. This study aims to assess the effectiveness of mass treatment and factors that influence. Methods:The study design was cross-sectional study. Blood sampling performed at night in four selected villages with a number of samples for blood tests as many as 1,209 people. Results:The numb...

  15. Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of medium-chain fatty acids with di- or tri-esters

    OpenAIRE

    Darshil P Patel; Ping Li; Abu T. M. Serajuddin

    2012-01-01

    To develop strategies for selecting appropriate lipids from mono-, di- and tri-esters of medium-chain fatty acids for the development of lipid-based drug delivery systems, ternary phase diagrams of propylene glycol(PG) monocaprylate (Capryol® 90; HLB~7), PG dicaprylocaprate (Labrafac™PG; HLB~2) and glycerol tricaprylocaprate (Labrafac™Lipophile WL1349; HLB~2) were determined in combination with a commonsurfactant, PEG-35 castor oil (Cremophor®EL, HLB~13), and water. Particle size and v...

  16. Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

    OpenAIRE

    Burgos, Jose L.; Patterson, Thomas L.; Joshua S Graff-Zivin; James G Kahn; Rangel, M. Gudelia; Lozada, M. Remedios; Staines, Hugo; Steffanie A Strathdee

    2016-01-01

    Background We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS) to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs) in Tijuana (TJ) and Ciudad-Juarez (CJ) Mexico. Data for this analysis was obtained from a factorial RCT in 2008–2010 coinciding with expansion of needle exchange programs (NEP) in TJ, but not in CJ. Methods A Markov model was develop...

  17. Newest-generation drug-eluting and bare-metal stents combined with prasugrel-based antiplatelet therapy in large coronary arteries

    DEFF Research Database (Denmark)

    Jeger, Raban; Pfisterer, Matthias; Alber, Hannes; Eberli, Franz; Galatius, Søren; Naber, Christoph; Pedrazzini, Giovanni; Rickli, Hans; Jensen, Jan Skov; Vuilliomenet, André; Gilgen, Nicole; Kaiser, Christoph

    2012-01-01

    In the BAsel Stent Kosten Effektivitäts Trial PROspective Validation Examination (BASKET-PROVE), drug-eluting stents (DESs) had similar 2-year rates of death and myocardial infarction but lower rates of target vessel revascularization and major adverse cardiac events compared with bare-metal sten...... (BMSs). However, comparative clinical effects of newest-generation DES with biodegradable polymers vs second-generation DES or newest-generation BMS with biocompatible coatings, all combined with a prasugrel-based antiplatelet therapy, on 2-year outcomes are not known....

  18. CONCEPT OF DRUG INTERACTION

    OpenAIRE

    Singh Nidhi

    2012-01-01

    Drug interaction is an increasingly important cause of adverse reactions (ADR), and is the modification of the effect of one drug (object) by the prior or concomitant administration of another drug (precipitant drug). Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin) are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or act...

  19. Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees.

    Science.gov (United States)

    Guseman, Alex J; Miller, Kaliah; Kunkle, Grace; Dively, Galen P; Pettis, Jeffrey S; Evans, Jay D; vanEngelsdorp, Dennis; Hawthorne, David J

    2016-01-01

    Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID:26840460

  20. Dispersion of hydrophobic magnetic nanoparticles using ultarsonic-assisted in combination with coacervative microextraction for the simultaneous preconcentration and determination of tricyclic antidepressant drugs in biological fluids.

    Science.gov (United States)

    Jannesar, Ramin; Zare, Fahimeh; Ghaedi, Mehrorang; Daneshfar, Ali

    2016-09-01

    A two-step sample preparation technique based on dispersive micro solid-phase extraction combined with coacervative microextraction is presented for preconcentration and determination of tricyclic antidepressant drugs in biological samples. An important feature of the method is the application of hydrophobic magnetic nanoparticles, which in combination with coacervative microextraction method enables development of rapid and efficient extraction procedure in order to achievement of a high extraction efficiency. Simultaneous optimization by experimental design lead to improvement of method with low cost which supply useful information about interaction among variables. Under the optimized conditions, a linear range of 5-1000ngmL(-1) with detection limits from 0.51 to 1.4ngmL(-1) were obtained for target analytes. The method was successfully used for the determination of analytes in biological fluids (plasma and urine) with relative recoveries in the range of 89-105% (RSDs<3.5%). PMID:27150784

  1. Development of an HPLC-UV Method for the Analysis of Drugs Used for Combined Hypertension Therapy in Pharmaceutical Preparations and Human Plasma

    Directory of Open Access Journals (Sweden)

    Serife Evrim Kepekci Tekkeli

    2013-01-01

    Full Text Available A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML, olmesartan medoxomil (OLM, valsartan (VAL, and hydrochlorothiazide (HCT in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I and AML, VAL, and HCT (combination II. The separation was achieved by using an RP-CN column, and acetonitrile-methanol-10 mmol orthophosphoric acid pH 2.5 (7 : 13 : 80, v/v/v was used as a mobile phase; the detector wavelength was set at 235 nm. The linear ranges were found as 0.1–18.5 μg/mL, 0.4–25.6 μg/mL, 0.3–15.5 μg/mL, and 0.3–22 μg/mL for AML, OLM, VAL, and HCT, respectively. In order to check the selectivity of the method for pharmaceutical preparations, forced degradation studies were carried out. According to the validation studies, the developed method was found to be reproducible and accurate as shown by RSD ≤6.1%, 5.7%, 6.9%, and 4.6% and relative mean error (RME ≤10.6%, 5.8%, 6.5%, and 6.8% for AML, OLM, VAL, and HCT, respectively. Consequently, the method was applied to the analysis of tablets and plasma of the patients using drugs including those substances.

  2. Development of an HPLC-UV Method for the Analysis of Drugs Used for Combined Hypertension Therapy in Pharmaceutical Preparations and Human Plasma.

    Science.gov (United States)

    Kepekci Tekkeli, Serife Evrim

    2013-01-01

    A simple, rapid, and selective HPLC-UV method was developed for the determination of antihypertensive drug substances: amlodipine besilat (AML), olmesartan medoxomil (OLM), valsartan (VAL), and hydrochlorothiazide (HCT) in pharmaceuticals and plasma. These substances are mostly used as combinations. The combinations are found in various forms, especially in current pharmaceuticals as threesome components: OLM, AML, and HCT (combination I) and AML, VAL, and HCT (combination II). The separation was achieved by using an RP-CN column, and acetonitrile-methanol-10 mmol orthophosphoric acid pH 2.5 (7 : 13 : 80, v/v/v) was used as a mobile phase; the detector wavelength was set at 235 nm. The linear ranges were found as 0.1-18.5  μ g/mL, 0.4-25.6  μ g/mL, 0.3-15.5  μ g/mL, and 0.3-22  μ g/mL for AML, OLM, VAL, and HCT, respectively. In order to check the selectivity of the method for pharmaceutical preparations, forced degradation studies were carried out. According to the validation studies, the developed method was found to be reproducible and accurate as shown by RSD ≤6.1%, 5.7%, 6.9%, and 4.6% and relative mean error (RME) ≤10.6%, 5.8%, 6.5%, and 6.8% for AML, OLM, VAL, and HCT, respectively. Consequently, the method was applied to the analysis of tablets and plasma of the patients using drugs including those substances. PMID:23634320

  3. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia;

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points.......08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. CONCLUSIONS: In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable...

  4. A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole

    Directory of Open Access Journals (Sweden)

    Agnik Pal

    2014-11-01

    Full Text Available A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but with different molecules of fluoroquinolone (ciprofloxacin or ofloxacin and nitroimidazole (tinidazole or ornidazole.He could not however avoid the rash. This time the patient presented with multiple, round-to-oval, well-defined, hyperpigmented cutaneous patches of different dimensions, all over the body. He appeared to have run out of options and therefore consulted us seeking advice on how he should treat himself next time he suffered from diarrhea. Causality assessment by Naranjo’s algorithm revealed a definite relationship between the cutaneous adverse reaction and the offending drug. He was counselled regarding medication in general and advised, in particular, to avoid the tendency to self-treat any future episode of diarrhea.

  5. Enhanced microemulsion formation in lipid-based drug delivery systems by combining mono-esters of medium-chain fatty acids with di- or tri-esters

    Directory of Open Access Journals (Sweden)

    Darshil P Patel

    2012-06-01

    Full Text Available To develop strategies for selecting appropriate lipids from mono-, di- and tri-esters of medium-chain fatty acids for the development of lipid-based drug delivery systems, ternary phase diagrams of propylene glycol(PG monocaprylate (Capryol® 90; HLB~7, PG dicaprylocaprate (Labrafac™PG; HLB~2 and glycerol tricaprylocaprate (Labrafac™Lipophile WL1349; HLB~2 were determined in combination with a commonsurfactant, PEG-35 castor oil (Cremophor®EL, HLB~13, and water. Particle size and viscosity in different regions of the phase diagrams were measured, solubility of a model drug, danazol, in different lipid-surfactant mixtures was determined, and dispersion testing by diluting selected preconcentrates with 250 ml 0.01 NHCl was performed. Further, phase diagrams were constructed using binary mixtures of lipids (monoester with diester, or monoester with triester in place of single lipids. The phase diagrams of PG dicaprylocaprate andglycerol tricaprylocaprate were similar, while it was distinctly different for PG monocaprylate. The microemulsion regions in phase diagrams were rather limited for individual lipids, and additionally, the diand tri-esters showed pronounced gel regions in the phase diagrams, which could influence drug release from preconcentrates. The mixing of PG monocaprylate (monoester with PG dicaprylocaprate (diester or glycerol tricaprylocaprate (triester had dramatic effects on the performance of lipids as evidenced by thegreatly reduced gel phases, much larger microemulsion regions, faster dispersion of the preconcentrates in an aqueous medium, and smaller particle size of the microemulsions subsequently formed.

  6. A Case of Self-treatment Induced Recurrent Fixed Drug Eruptions Associated with the Use of Different Fixed Dose Combinations of Fluoroquinolone-Nitroimidazole.

    Science.gov (United States)

    Pal, Agnik; Sen, Sukanta; Das, Suvajit; Biswas, Arunava; Tripathi, Santanu K

    2014-11-01

    A young male patient used fixed dose combinations of different fluoroquinolones and nitroimidazoles several times in the last few years for self-treating repeated episodes of diarrhea and loose motion. Each time, he experienced fixed drug eruptions that increased in number and severity on subsequent occasions. Suspecting association between the drug and the rashes, the patient each time discontinued the treatment prematurely, and preferred to switch to a similar formulation next time, but with different molecules of fluoroquinolone (ciprofloxacin or ofloxacin) and nitroimidazole (tinidazole or ornidazole). He could not however avoid the rash. This time the patient presented with multiple, round-to-oval, well-defined, hyperpigmented cutaneous patches of different dimensions, all over the body. He appeared to have run out of options and therefore consulted us seeking advice on how he should treat himself next time he suffered from diarrhea. Causality assessment by Naranjo's algorithm revealed a definite relationship between the cutaneous adverse reaction and the offending drug. He was counselled regarding medication in general and advised, in particular, to avoid the tendency to self-treat any future episode of diarrhea. PMID:25429184

  7. Preclinical Evaluation on the Tumor Suppression Efficiency and Combination Drug Effects of Fermented Wheat Germ Extract in Human Ovarian Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chia-Woei Wang

    2015-01-01

    Full Text Available Fermented wheat germ extract (FWGE is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced programmed cell death by activating the caspase-7 cleavage in both SKOV-3 and ES-2 cells, but only caspase-3 and poly(adenosine diphosphate-ribose polymerase cleavages were activated in SKOV-3 cells. Moreover, FWGE exhibited combination drug effects with cisplatin and docetaxel in SKOV-3 and ES-2 cells by enhancing the cytotoxicity of both drugs. In conclusion, we found that FWGE not only suppressed cell growth but also induced caspase-3-related and caspase-7-related cell death in human ovarian carcinoma cells. FWGE treatment further enhanced the cytotoxicity of cisplatin and docetaxel, suggesting that FWGE is a potential ingredient in the development of adjuvant chemotherapy with cisplatin or docetaxel for treating ovarian cancer patients.

  8. 喹诺酮类药物的耐药、联合用药及不良反应分析%Analysis of drug resistance,drug combination and adverse reactions of quinolones

    Institute of Scientific and Technical Information of China (English)

    孙志勇

    2013-01-01

    目的研究喹诺酮类药物的耐药、联合用药和不良反应。方法对本院应用喹诺酮类药物治疗后出现不良反应的60例患者的临床资料进行回顾性分析。结果常见的不良反应主要为全身性损伤(14例,23.4%)、皮肤方面的损伤(12例,20.0%)和神经系统损伤(18例,30.0%)。喹诺酮类药物目前的耐药情况比较严重。结论喹诺酮类药物应合理使用,并掌握其临床适应证以及剂量,尽可能避免联合用药的不合理性和不良反应的发生。%Objective To investigate the resistance,drug combination and adverse reactions of quinolones. Methods Clinical data of 60 patients who had adverse reactions after using quinolones in our hospital were collected and analyzed retrospectively. Results The main common adverse reactions were systemic injury(14 patients,23.4%),skin injury (12 patients,20.0%) and nervous system injury(18 patients,30.0%). The current drug resistance situation of quinolones was severe. Conclusion Quinolones should be used rationally and their clinical indications and doses should be mastered in order to avoid the irrationality of drug combination and the occurrence of adverse reactions.

  9. Rotational atherectomy using small burr combined with drug-eluting stent implantation for the treatment of heavily calcified coronary lesions: analysis of clinical outcomes

    International Nuclear Information System (INIS)

    Objective: To investigate the safety and efficacy of rotational atherectomy with small burr together with subsequent drug-eluting stent implantation in treating patients with heavily calcified coronary lesions. Methods: During the period from January 2009 to April 2013 a total of 12 patients with heavily calcified coronary lesions were admitted to authors' hospital. The diagnosis was confirmed by angiography in all patients. Rotational atherectomy with small bun combined with subsequent drug-eluting stent implantation were carried out. The clinical data, including angiography success rate, procedure success rate, complications and postoperative main adverse cardiovascular events such as death, myocardial infarction and target lesion revascularization, etc. were retrospectively analyzed. Results: A total of sixteen heavily calcified lesions of Type C in 12 patients were successfully treated with rotational atherectomy and drug-eluting stent placement. After rotational atherectomy the stenosis degree of the coronary artery decreased from preoperative (82.7±7.6)% to postoperative (35.2±10.3)%, the difference between the two was statistically significant (P<0.05), and a total of 22 drug-eluting stents were successfully implanted. The angiography success rate was 100%. The average burr-to-artery ratio used in the procedure was (0.50±0.02), the bun with the diameter ≤1.50 mm was employed in treating 93.7% of lesions (15/16). The success rate of the procedure was 91.7% (11/12). During the procedure stasis of blood flow was observed in one patient, and the patient developed perioperative myocardial infarction. No acute vascular occlusion, coronary perforation, dissection or death occurred, and no patient needed to receive emergency coronary artery bypass grafting. All the patients were followed up for (7.1±2.5) months, and no recurrence of angina pectoris or major cardiovascular event was observed. Conclusion: For the treatment of heavily calcified coronary

  10. Artemether-Lumefantrine Combination Therapy for Treatment of Uncomplicated Malaria: The Potential for Complex Interactions with Antiretroviral Drugs in HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Pauline Byakika-Kibwika

    2011-01-01

    Full Text Available Treatment of malaria in HIV-infected individuals receiving antiretroviral therapy (ART poses significant challenges. Artemether-lumefantrine (AL is one of the artemisisnin-based combination therapies recommended for treatment of malaria. The drug combination is highly efficacious against sensitive and multidrug resistant falciparum malaria. Both artemether and lumefantrine are metabolized by hepatic cytochrome P450 (CYP450 enzymes which metabolize the protease inhibitors (PIs and nonnucleoside reverse transcriptase inhibitors (NNRTIs used for HIV treatment. Coadministration of NNRTIs and PIs with AL could potentially cause complex pharmacokinetic drug interactions. NNRTI by inducing CYP450 3A4 enzyme and PIs by inhibiting CYP450 3A4 enzymes could influence both artemether and lumefantrine concentrations and their active metabolites dihydroartemisinin and desbutyl-lumefantrine, predisposing patients to poor treatment response, toxicity, and risk for development of resistance. There are scanty data on these interactions and their consequences. Pharmacokinetic studies to evaluate these interactions in the target populations are urgently needed.

  11. Desensitization therapy using laser, drug or their combination to treat dentine hypersentitivity: a review%激光联合药物脱敏的研究进展

    Institute of Scientific and Technical Information of China (English)

    郭蓝; 陈新梅

    2012-01-01

    牙本质敏感是口腔临床上的常见病、多发病之一,其发病机制尚不清楚,而且,目前临床上仍没有理想的脱敏方法.激光联合药物脱敏克服了单一脱敏方法的不足,提高了脱敏效果,已成为近年来牙本质敏感治疗研究的焦点.本文对激光联合药物脱敏的研究进展作一综述.%Dentine hypersensitivity (DH) is one of the most common clinical oral diseases, yet its patho-genesis is not clear. There is no ideal clinical desensitization therapy at present . The combination of laser and drug o-vercame the drawbacks of single laser or drug therapy, and improved the desensitization effect. It has become the focus of the treatment of DH. In this article, the progress of desensitization therapies using laser, medicine and its combination is summarized.

  12. Combining Non-pharmacological Treatments with Pharmacotherapies for Neurological Disorders: a Unique Interface of the Brain, Drug-Device and Intellectual Property

    Directory of Open Access Journals (Sweden)

    Grzegorz eBulaj

    2014-07-01

    Full Text Available Mobile medical applications (mHealth, music and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engage an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug-device therapies may be offset by a value proposition of the exclusivity due to the patent-independent protection which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies, and their combinations with pharmacotherapies, offers incentives to chronically-ill patients and outcome-driven health care industries.

  13. Combining non-pharmacological treatments with pharmacotherapies for neurological disorders: a unique interface of the brain, drug-device, and intellectual property.

    Science.gov (United States)

    Bulaj, Grzegorz

    2014-01-01

    Mobile medical applications (mHealth), music, and video games are being developed and tested for their ability to improve pharmacotherapy outcomes and medication adherence. Pleiotropic mechanism of music and gamification engages an intrinsic motivation and the brain reward system, supporting therapies in patients with neurological disorders, including neuropathic pain, depression, anxiety, or neurodegenerative disorders. Based on accumulating results from clinical trials, an innovative combination treatment of epilepsy seizures, comorbidities, and the medication non-adherence can be designed, consisting of antiepileptic drugs and disease self-management software delivering clinically beneficial music. Since creative elements and art expressed in games, music, and software are copyrighted, therefore clinical and regulatory challenges in developing copyrighted, drug-device therapies may be offset by a value proposition of the exclusivity due to the patent-independent protection, which can last for over 70 years. Taken together, development of copyrighted non-pharmacological treatments (e-therapies), and their combinations with pharmacotherapies, offer incentives to chronically ill patients and outcome-driven health care industries. PMID:25071711

  14. From Bench-Top to Bedside: A Prospective In Vitro Antibiotic Combination Testing (iACT) Service to Guide the Selection of Rationally Optimized Antimicrobial Combinations against Extensively Drug Resistant (XDR) Gram Negative Bacteria (GNB)

    Science.gov (United States)

    Lim, Tze-Peng; Teo, Jocelyn Qi-Min; Lee, Winnie; Kurup, Asok; Koh, Tse-Hsien; Tan, Thuan-Tong; Kwa, Andrea L.

    2016-01-01

    Introduction Combination therapy is increasingly utilized against extensively-drug resistant (XDR) Gram negative bacteria (GNB). However, choosing a combination can be problematic as effective combinations are often strain-specific. An in vitro antibiotic combination testing (iACT) service, aimed to guide the selection of individualized and rationally optimized combination regimens within 48 hours, was developed. We described the role and feasibility of the iACT service in guiding individualized antibiotic combination selection in patients with XDR-GNB infections. Methods A retrospective case review was performed in two Singapore hospitals from April 2009–June 2014. All patients with XDR-GNB and antibiotic regimen guided by iACT for clinical management were included. The feasibility and role of the prospective iACT service was evaluated. The following patient outcomes were described: (i) 30-day in-hospital all-cause and infection-related mortality, (ii) clinical response, and (iii) microbiological eradication in patients with bloodstream infections. Results From 2009–2014, the iACT service was requested by Infectious Disease physicians for 39 cases (20 P. aeruginosa, 13 A. baumannii and 6 K. pneumoniae). Bloodstream infection was the predominant infection (36%), followed by pneumonia (31%). All iACT recommendations were provided within 48h from request for the service. Prior to iACT-guided therapy, most cases were prescribed combination antibiotics empirically (90%). Changes in the empiric antibiotic regimens were recommended in 21 (54%) cases; in 14 (36%) cases, changes were recommended as the empiric regimens were found to be non-bactericidal in vitro. In 7 (18%) cases, the number of antibiotics used in combination empirically was reduced by the iACT service. Overall, low 30-day infection-related mortality (15%) and high clinical response (82%) were observed. Microbiological eradication was observed in 79% of all bloodstream infections. Conclusions The i

  15. Chinese Patent Medicine Liu Wei Di Huang Wan Combined with Antihypertensive Drugs, a New Integrative Medicine Therapy, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

    OpenAIRE

    Jie Wang; Kuiwu Yao; Xiaochen Yang; Wei Liu; Bo Feng; Jizheng Ma; Xinliang Du; Pengqian Wang; Xingjiang Xiong

    2012-01-01

    Objectives. To assess the beneficial and adverse effects of Liu Wei Di Huang Wan (LWDHW), combined with antihypertensive drugs, for essential hypertension. Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of LWDHW combined with antihypertensive drugs for essential hypertension reported in any language, with main outcome measures as blood pressure. The quality of the i...

  16. Piloting the global subsidy: the impact of subsidized artemisinin-based combination therapies distributed through private drug shops in rural Tanzania.

    Directory of Open Access Journals (Sweden)

    Oliver J Sabot

    Full Text Available WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs, partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania.Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001, and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005. No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001.A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently.Controlled-Trials.com ISRCTN39125414.

  17. Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed through Private Drug Shops in Rural Tanzania

    Science.gov (United States)

    Sabot, Oliver J.; Mwita, Alex; Cohen, Justin M.; Ipuge, Yahya; Gordon, Megumi; Bishop, David; Odhiambo, Moses; Ward, Lorrayne; Goodman, Catherine

    2009-01-01

    Background WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. Methods/Principal Findings Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting interventions. From October 2007, ACTs were sold at a 90% subsidy through the normal private supply chain to intervention district drug shops. Data were collected at baseline and during intervention using interviews with drug shop customers, retail audits, mystery shoppers, and audits of public and NGO facilities. The proportion of consumers in the intervention districts purchasing ACTs rose from 1% at baseline to 44.2% one year later (p<0.001), and was significantly higher among consumers purchasing for children under 5 than for adults (p = 0.005). No change in ACT usage was observed in the control district. Consumers paid a mean price of $0.58 for ACTs, which did not differ significantly from the price paid for sulphadoxine-pyrimethamine, the most common alternative. Drug shops in population centers were significantly more likely to stock ACTs than those in more remote areas (p<0.001). Conclusions A subsidy introduced at the top of the private sector supply chain can significantly increase usage of ACTs and reduce their retail price to the level of common monotherapies. Additional interventions may be needed to ensure access to ACTs in remote areas and for poorer individuals who appear to seek treatment at drug shops less frequently. Trial Registration Controlled-Trials.com ISRCTN39125414. PMID:19724644

  18. A pharmacy too far? Equity and spatial distribution of outcomes in the delivery of subsidized artemisinin-based combination therapies through private drug shops

    Directory of Open Access Journals (Sweden)

    Ward Lorrayne

    2010-07-01

    Full Text Available Abstract Background Millions of individuals with malaria-like fevers purchase drugs from private retailers, but artemisinin-based combination therapies (ACTs, the only effective treatment in regions with high levels of resistance to older drugs, are rarely obtained through these outlets due to their relatively high cost. To encourage scale up of ACTs, the Affordable Medicines Facility – malaria is being launched to subsidize their price. The Government of Tanzania and the Clinton Foundation piloted this subsidized distribution model in two Tanzanian districts to examine concerns about whether the intervention will successfully reach poor, rural communities. Methods Stocking of ACTs and other antimalarial drugs in all retail shops was observed at baseline and in four subsequent surveys over 15 months. Exit interviews were conducted with antimalarial drug customers during each survey period. All shops and facilities were georeferenced, and variables related to population density and proximity to distribution hubs, roads, and other facilities were calculated. To understand the equity of impact, shops stocking ACTs and consumers buying them were compared to those that did not, according to geographic and socioeconomic variables. Patterning in ACT stocking and sales was evaluated against that of other common antimalarials to identify factors that may have impacted access. Qualitative data were used to assess motivations underlying stocking, distribution, and buying disparities. Results Results indicated that although total ACT purchases rose from negligible levels to nearly half of total antimalarial sales over the course of the pilot, considerable geographic variation in stocking and sales persisted and was related to a variety of socio-spatial factors; ACTs were stocked more often in shops located closer to district towns (p Conclusions As this subsidy model is scaled up across multiple countries, these results confirm the potential for increased

  19. Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model.

    Directory of Open Access Journals (Sweden)

    Bing Fan

    Full Text Available Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB. Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC for meropenem (MIC ≤ 32 mg/L, combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings.

  20. Activity of Colistin in Combination with Meropenem, Tigecycline, Fosfomycin, Fusidic Acid, Rifampin or Sulbactam against Extensively Drug-Resistant Acinetobacter baumannii in a Murine Thigh-Infection Model

    Science.gov (United States)

    Wang, Xiumei; Cong, Yulong

    2016-01-01

    Few effective therapeutic options are available for treating severe infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). Using a murine thigh-infection model, we examined the in vivo efficacy of colistin in combination with meropenem, tigecycline, fosfomycin, fusidic acid, rifampin, or sulbactam against 12 XDR-AB strains. Colistin, tigecycline, rifampin, and sulbactam monotherapy significantly decreased bacterial counts in murine thigh infections compared with those observed in control mice receiving no treatment. Colistin was the most effective agent tested, displaying bactericidal activity against 91.7% of strains at 48 h post-treatment. With strains showing a relatively low minimum inhibitory concentration (MIC) for meropenem (MIC ≤ 32 mg/L), combination therapy with colistin plus meropenem caused synergistic inhibition at both 24 h and 48 h post-treatment. However, when the meropenem MIC was ≥64 mg/L, meropenem did not significantly alter the efficacy of colistin. The addition of rifampin and fusidic acid significantly improved the efficacy of colistin, showing a synergistic effect in 100% and 58.3% of strains after 24 h of treatment, respectively, while the addition of tigecycline, fosfomycin, or sulbactam did not show obvious synergistic activity. No clear differences in activities were observed between colistin-rifampin and colistin-fusidic acid combination therapy with most strains. Overall, our in vivo study showed that administering colistin in combination with rifampin or fusidic acid is more efficacious in treating XDR-AB infections than other combinations. The colistin-meropenem combination may be another appropriate option if the MIC is ≤32 mg/L. Further clinical studies are urgently needed to confirm the relevance of these findings. PMID:27315107

  1. Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

    International Nuclear Information System (INIS)

    Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19

  2. Enhanced activity of carbosilane dendrimers against HIV when combined with reverse transcriptase inhibitor drugs: searching for more potent microbicides

    Directory of Open Access Journals (Sweden)

    Vacas-Córdoba E

    2014-07-01

    Full Text Available Enrique Vacas-Córdoba,1–3 Marta Galán,3,4 Francisco J de la Mata,3,4 Rafael Gómez,3,4 Marjorie Pion,1–3 M Ángeles Muñoz-Fernández1–3 1Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 2Instituto de Investigación Sanitaria del Gregorio Marañón, Madrid, Spain; 3Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN, Madrid, Spain; 4Dendrimers for Biomedical Applications Group (BioInDen, University of Alcalá, Madrid, Spain Abstract: Self-administered topical microbicides or oral preexposure prophylaxis could be very helpful tools for all risk groups to decrease the human immunodeficiency virus (HIV-1 infection rates. Up until now, antiretrovirals (ARVs have been the most advanced microbicide candidates. Nevertheless, the majority of clinical trials has failed in HIV-1 patients. Nanotechnology offers suitable approaches to develop novel antiviral agents. Thereby, new nanosystems, such as carbosilane dendrimers, have been shown to be safe and effective compounds against HIV with great potential as topical microbicides. In addition, because most of the attempts to develop effective topical microbicides were unsuccessful, combinatorial strategies could be a valid approach when designing new microbicides. We evaluated various combinations of anionic carbosilane dendrimers with sulfated (G3-S16 and naphthyl sulfonated (G2-NF16 ended groups with different ARVs against HIV-1 infection. The G3-S16 and G2-NF16 dendrimers showed a synergistic or additive activity profile with zidovudine, efavirenz, and tenofovir in the majority of the combinations tested against the X4 and R5 tropic HIV-1 in cell lines, as well as in human primary cells. Therefore, the combination of ARVs and polyanionic carbosilane dendrimers enhances the antiviral potency of the individual compounds, and our findings support further clinical research on combinational approaches as

  3. Comparison of fixed topical combination glaucoma drugs in patients with open-angle glaucomsa or ocular hypertension

    OpenAIRE

    BAKHRITDINOVA FAZILAT ARIFOVNA; KARIMOV ULUGBEK RASULOVICH; MIRRAKHIMOVA SAIDA SH.; AKSHEY KHERA

    2016-01-01

    The purpose of study was to compare the intraocular pressure lowering efficacy, safety and cost-efficiency of fixed combinations travoprost 0.004 %/timolol 0.5 % (tim + tarv), brimonidine 0.2 %/timolo0.5 % (tim + brim), brinzolamide 1 %/timolol 0.5 % (tim + brinz) and pilocarpin 2 %/timolol 0.5 % (tim + pil) in patients with ocular hypertension or open-angle glaucoma. In this prospective, randomized clinical trial included 80 qualifying patients (4 groups) during six month. It was found that ...

  4. Effectiveness of two rounds of mass drug administration using DEC combined with albendazole on the prevalence of Brugia malayi

    Directory of Open Access Journals (Sweden)

    Santoso Santoso

    2015-11-01

    Full Text Available Background: Filariasis mass drug administration carried out for 5 consecutive years aims to reduce the prevalence rate of < 1%. Evaluation of treatment needs to be done, one of them with a finger blood survey. This study aims to assess the effectiveness of mass treatment and factors that influence. Methods:The study design was cross-sectional study. Blood sampling performed at night in four selected villages with a number of samples for blood tests as many as 1,209 people. Results:The number of microfilaria positive population of 10 people. The Village with the most number of cases (6 people with a microfilaria rate of 2.08% is Nibung Putih villages. History of fever, behavior taking medication, age and gender related to the incidence of filariasis. Regency East Tanjung Jabung is endemic filariasis because they found villages with Mf rate > 1%. Conclusions: Implementation of filariasis mass treatment was less effective because they can not derive filariasis endemicity. Recommendation: Implementation of filariasis mass treatment needs to be improved by increasing the participation of local community leaders in order to reach all levels of society, including isolated communities.

  5. A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the Treatment of Multivessel Coronary Artery Disease.

    Science.gov (United States)

    Al-Mamary, Ahmed; Zilio, Filippo; Napodano, Massimo

    2016-08-01

    Optimal management of multivessel coronary artery disease can be complex. We report a 67-year-old male patient who was admitted to the Padua University Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction. Coronary angiography showed diffuse multiple sub-occlusive lesions of the proximal and distal left coronary vessels involving a long segment of the vessel. On intravascular ultrasonography (IVUS), the left main artery was moderately diseased with critically stenotic and calcified branch ostia. A successful percutaneous coronary intervention using the T-stenting and small protrusion technique with two drug-eluting stents (DES) was performed on the left main artery and its main branches. Two bioresorbable vascular scaffolds were also deployed in overlap at the mid to distal segments of the left anterior descending artery and overlapping a previous DES at the proximal segment. The full expansion and apposition of the struts and scaffolds to the vessel wall without residual stenosis was confirmed by IVUS. PMID:27606119

  6. The effects in mice of combined treatments to X-rays and antineoplastic drugs in the Comet assay

    International Nuclear Information System (INIS)

    The Comet assay is a rapid, easy and reproducible method to detect genotoxic activity of chemical and physical agents in vitro and in vivo. In the present study the effects of exposure to irradiation or chemicals: cyclophosphamide (CP) and mitomycin C (MMC) or combined exposure to low doses of both agents (0.25 Gy + 3.15 mg/kg bw CP and 0.25 Gy + 0.25 mg/kg bw MMC) were examined for the induction of DNA damage in the Comet assay measured simultaneously in somatic (bone marrow lymphocytes) and haploid germ cells. The male mice were treated in vivo and sacrificed at 24 h after exposure. The percentage contents of DNA in the 'comet tail' increased with increasing doses of X-rays and chemicals. After combined exposure to X-rays and CP and to X-rays and MMC weak increases of DNA damage in bone marrow lymphocytes and in germ cells were observed by comparison with the results obtained for each agent acting alone. There were slightly different responses in bone marrow lymphocytes and in germ cells, but effects were observed over a similar dose range

  7. Intraocular pressure-lowering effects of commonly used fixed-combination drugs with timolol: a systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jin-Wei Cheng

    Full Text Available BACKGROUND: The first goal of medical therapy in glaucoma is to reduce intraocular pressure (IOP, and the fixed-combination medications are needed to achieve sufficiently low target IOP. The aim of this systematic review and meta-analysis is to evaluate IOP-lowering effect of the commonly used fixed-combination drugs containing 0.5% timolol. METHODS: Pertinent publications were identified through systematic searches. Over 85% of the patients had to be diagnosed with primary open-angle glaucoma (POAG or ocular hypertension (OHT. Forty-one randomized clinical trials were included in the meta-analysis. The main efficacy measures were the absolute and relative values of mean diurnal IOP reduction, and the highest and lowest IOP reductions on the diurnal IOP curve. The pooled 1- to 3-month IOP-lowering effects after a medicine-free washout period was calculated by performing meta-analysis using the random effects model, and relative treatment effects among different fixed combinations were assessed using a mixed-effects meta-regression model. RESULTS: The relative reductions for mean diurnal IOP were 34.9% for travoprost/timolol, 34.3% for bimatoprost/timolol, 33.9% for latanoprost/timolol, 32.7% for brinzolamide/timolol, 29.9% for dorzolamide/timolol, and 28.1% for brimonidine/timolol. For the highest IOP decrease, relative reductions ranged from 31.3% for dorzolamide/timolol to 35.5% for travoprost/timolol; for the lowest IOP decrease, those varied from 25.9% for dorzolamide/timolol to 33.1% for bimatoprost/timolol. Both latanoprost/timolol and travoprost/timolol were more effective in lowering mean diurnal IOP than brimonidine/timolol (WMD: 5.9 and 7.0 and dorzolamide/timolol (WMD: 3.8 and 3.3. CONCLUSIONS: All six commonly used fixed-combination drugs containing timolol can effectively lower IOP in patients with POAG and OHT, and both latanoprost/timolol and travoprost/timolol might achieve better IOP-lowering effects among the six fixed-combination

  8. Biodistribution study of [99mTc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography

    International Nuclear Information System (INIS)

    A 99mTc labeled tropane derivative, [99mTc] TRODAT-1 (2β-((N,N'-bis(2-mercaptoethyl) ethylene diamino)methyl), 3β-(4-chlorophenyl) tropane), is a potential dopamine transporter (DAT) imaging agent for the central nervous system. To better understand the binding localization of [99mTc] TRODAT-1 both in the brain and the body, whole-body macroautoradiography (WBAR) was used in this study. The effect of DAT competing drugs, such as levadopa (L-DOPA), N-methyl-2β-carbomethoxy-3β-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [99mTc] TRODAT-1 were also included in this study. Doses of 150 MBq [99mTc] TRODAT-1 were injected into normal male ICR mice through the caudal veins. For comparison, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), L-DOPA, methylphenidate and CFT, respectively, were also investigated under the similar protocols. One and a half hours after [99mTc] TRODAT-1 injection, the mice were sacrificed. Whole-body autoradiography was performed immediately after sacrifice. Both frontal and sagittal sections showed that the liver and mucosa of stomach had the highest uptake of [99mTc] TRODAT-1. Other binding sites included the periphery of the spinal cord and the epithelium of the intestine. In the brain, autoradiographic imaging obtained from frontal sections showed symmetrical uptakes of [99mTc] TRODAT-1 in bilateral striata. Remaining binding sites include olfactory bulbs, thyroid gland, and salivary gland. The autoradiographic imaging obtained from sagittal sections showed a similar biodistribution. Mice treated with MPTP or L-DOPA showed no significant difference in the uptake of [99mTc] TRODAT-1 in bilateral striata, as compared to those of the control. In CFT or methylphenidate-treated mice, DAT binding sites were almost completely inhibited. These data showed that [99mTc] TRODAT-1 has potential clinical use for neurological investigation, such as Parkinson's and similar diseases

  9. Antibacterial Activity of Protocatechuic Acid Ethyl Ester on Staphylococcus aureus Clinical Strains Alone and in Combination with Antistaphylococcal Drugs

    Directory of Open Access Journals (Sweden)

    Maria Miklasińska

    2015-07-01

    Full Text Available The aim of the presented study was to examine in vitro the antibacterial activity of protocatechuic acid ethyl ester (ethyl 3,4-dihydroxybenzoate, EDHB against Staphylococcus aureus clinical isolates alone and in the combination with four selected antibiotics. The EDHB antimicrobial activity was tested against twenty S. aureus strains isolated from the clinical samples, and three reference strains. The phenotypes and genotypes of resistance to methicillin for the tested strains were defined as well as the phenotypic resistance to macrolides, lincosamides and streptogramin B (MLSB. EDHB displayed diverse activity against examined S. aureus strains with the minimal inhibitory concentration (MIC within the range from 64 to 1024 µg/mL. Addition of ¼ MIC of EDHB into the Mueller-Hinton Agar (MHA resulted in augmented antibacterial effect in the presence of clindamycin. In the case of cefoxitin no synergistic effect with EDHB was noted. For erythromycin and vancomycin the decrease of mean MICs in the presence of EDHB was observed but did not reach statistical significance. The results of the present study showed that in vitro EDHB possesses antibacterial activity against S. aureus clinical strains and triggers a synergistic antimicrobial effect with clindamycin and to the lesser extent with erythromycin and vancomycin.

  10. Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures.

    Directory of Open Access Journals (Sweden)

    Alessandro Furlan

    Full Text Available The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by "RTK swapping" by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in

  11. The enhanced value of combining conventional and 'omics' analyses in early assessment of drug-induced hepatobiliary injury

    International Nuclear Information System (INIS)

    The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling ('omics') technologies. In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyzed in relation to routine clinical chemistry and histopathology. Four of the sixteen hepato- and/or nephrotoxicants given to rats for 1, 3, or 14 days at two dose levels induced similar histopathological effects. These were characterized by bile duct necrosis and hyperplasia and/or increased bilirubin and cholestasis, in addition to hepatocyte necrosis and regeneration, hepatocyte hypertrophy, and hepatic inflammation. Combined analysis of liver transcriptomics data from these studies revealed common gene expression changes which allowed the development of a potential sequence of events on a mechanistic level in accordance with classical endpoint observations. This included genes implicated in early stress responses, regenerative processes, inflammation with inflammatory cell immigration, fibrotic processes, and cholestasis encompassing deregulation of certain membrane transporters. Furthermore, a preliminary classification analysis using transcriptomics data suggested that prediction of cholestasis may be possible based on gene expression changes seen at earlier time-points. Targeted bile acid analysis, based on LC-MS metabonomics data demonstrating increased levels of conjugated or unconjugated bile acids in response to individual compounds, did not provide earlier detection of toxicity as compared to conventional parameters, but may allow distinction of different types of hepatobiliary toxicity. Overall, liver transcriptomics data delivered mechanistic and molecular details in addition to the classical endpoint observations which were further enhanced by targeted bile acid analysis using LC/MS metabonomics.

  12. Combining physical and virtual contexts through augmented reality: design and evaluation of a prototype using a drug box as a marker for antibiotic training.

    Science.gov (United States)

    Nifakos, Sokratis; Tomson, Tanja; Zary, Nabil

    2014-01-01

    Introduction. Antimicrobial resistance is a global health issue. Studies have shown that improved antibiotic prescription education among healthcare professionals reduces mistakes during the antibiotic prescription process. The aim of this study was to investigate novel educational approaches that through the use of Augmented Reality technology could make use of the real physical context and thereby enrich the educational process of antibiotics prescription. The objective is to investigate which type of information related to antibiotics could be used in an augmented reality application for antibiotics education. Methods. This study followed the Design-Based Research Methodology composed of the following main steps: problem analysis, investigation of information that should be visualized for the training session, and finally the involvement of the end users the development and evaluation processes of the prototype. Results. Two of the most important aspects in the antibiotic prescription process, to represent in an augmented reality application, are the antibiotic guidelines and the side effects. Moreover, this study showed how this information could be visualized from a mobile device using an Augmented Reality scanner and antibiotic drug boxes as markers. Discussion. In this study we investigated the usage of objects from a real physical context such as drug boxes and how they could be used as educational resources. The logical next steps are to examine how this approach of combining physical and virtual contexts through Augmented Reality applications could contribute to the improvement of competencies among healthcare professionals and its impact on the decrease of antibiotics resistance. PMID:25548733

  13. High-dose antibiotic therapy is superior to a 3-drug combination of prostanoids and lipid A derivative in protecting irradiated canines

    International Nuclear Information System (INIS)

    There is an urgent need to develop non-toxic radioprotectors. We tested the efficacy of a 3-drug combination (3-DC) of iloprost, misoprostol, and 3D-MPL (3-deacylated monophosphoryl lipid A) and the effects of postirradiation clinical support with high doses of antibiotics and blood transfusion. Canines were given 3-DC or the vehicle and exposed to 3.4 Gy or 4.1 Gy of 60Co radiation. Canines irradiated at 4.1 Gy were also given clinical support, which consisted of blood transfusion and antibiotics (gentamicin, and cefoxitin or cephalexin). Peripheral blood cell profile and 60-day survival were used as indices of protection. At 3.4 Gy, 3-DC- or vehicle-treated canines without postirradiation clinical support survived only for 10 to 12 days. Fifty percent of the canines treated with 3-DC or vehicle and provided postirradiation clinical support survived 4.1-Gy irradiation. Survival of canines treated with vehicle before irradiation significantly correlated with postirradiation antibiotic treatments, but not with blood transfusion. The recovery profile of peripheral blood cells in 4.1 Gy-irradiated canines treated with vehicle and antibiotics was better than drug-treated canines. These results indicate that therapy with high doses of intramuscular aminoglycoside antibiotic (gentamicin) and an oral cephalosporin (cephalexin) enhanced survival of irradiated canines. Although blood transfusion correlated with survival of 3-DC treated canines, there were no additional survivors with 3-DC treated canines than the controls. (author)

  14. Combining physical and virtual contexts through augmented reality: design and evaluation of a prototype using a drug box as a marker for antibiotic training

    Directory of Open Access Journals (Sweden)

    Sokratis Nifakos

    2014-12-01

    Full Text Available Introduction. Antimicrobial resistance is a global health issue. Studies have shown that improved antibiotic prescription education among healthcare professionals reduces mistakes during the antibiotic prescription process. The aim of this study was to investigate novel educational approaches that through the use of Augmented Reality technology could make use of the real physical context and thereby enrich the educational process of antibiotics prescription. The objective is to investigate which type of information related to antibiotics could be used in an augmented reality application for antibiotics education. Methods. This study followed the Design-Based Research Methodology composed of the following main steps: problem analysis, investigation of information that should be visualized for the training session, and finally the involvement of the end users the development and evaluation processes of the prototype. Results. Two of the most important aspects in the antibiotic prescription process, to represent in an augmented reality application, are the antibiotic guidelines and the side effects. Moreover, this study showed how this information could be visualized from a mobile device using an Augmented Reality scanner and antibiotic drug boxes as markers. Discussion. In this study we investigated the usage of objects from a real physical context such as drug boxes and how they could be used as educational resources. The logical next steps are to examine how this approach of combining physical and virtual contexts through Augmented Reality applications could contribute to the improvement of competencies among healthcare professionals and its impact on the decrease of antibiotics resistance.

  15. MAGE-C2-Specific TCRs Combined with Epigenetic Drug-Enhanced Antigenicity Yield Robust and Tumor-Selective T Cell Responses.

    Science.gov (United States)

    Kunert, Andre; van Brakel, Mandy; van Steenbergen-Langeveld, Sabine; da Silva, Marvin; Coulie, Pierre G; Lamers, Cor; Sleijfer, Stefan; Debets, Reno

    2016-09-15

    Adoptive T cell therapy has shown significant clinical success for patients with advanced melanoma and other tumors. Further development of T cell therapy requires improved strategies to select effective, yet nonself-reactive, TCRs. In this study, we isolated 10 TCR sequences against four MAGE-C2 (MC2) epitopes from melanoma patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. We introduced these TCRs into T cells, pretreated tumor cells of different histological origins with the epigenetic drugs azacytidine and valproate, and tested tumor and self-reactivities of these TCRs. Pretreatment of tumor cells upregulated MC2 gene expression and enhanced recognition by T cells. In contrast, a panel of normal cell types did not express MC2 mRNA, and similar pretreatment did not result in recognition by MC2-directed T cells. Interestingly, the expression levels of MC2, but not those of CD80, CD86, or programmed death-ligand 1 or 2, correlated with T cell responsiveness. One of the tested TCRs consistently recognized pretreated MC2(+) cell lines from melanoma, head and neck, bladder, and triple-negative breast cancers but showed no response to MHC-eluted peptides or peptides highly similar to MC2. We conclude that targeting MC2 Ag, combined with epigenetic drug-enhanced antigenicity, allows for significant and tumor-selective T cell responses. PMID:27489285

  16. Method development and validation of liquid chromatography-tandem/mass spectrometry for aldosterone in human plasma: Application to drug interaction study of atorvastatin and olmesartan combination

    Directory of Open Access Journals (Sweden)

    Rakesh Das

    2014-01-01

    Full Text Available In the present investigation, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS method was developed for the quantification of aldosterone (ALD a hormone responsible for blood pressure in human plasma. The developed method was validated and extended for application on human subjects to study drug interaction of atorvastatin (ATSV and olmesartan (OLM on levels of ALD. The ALD in plasma was extracted by liquid-liquid extraction with 5 mL dichloromethane/ethyl ether (60/40% v/v. The chromatographic separation of ALD was carried on Xterra, RP-Column C18 (150 mm× 4.6 mm × 3.5 μm at 30°C followed by four-step gradient program composed of methanol and water. Step 1 started with 35% methanol for first 1 min and changed linearly to 90% in next 1.5 min in Step 2. Step 3 lasted for next 2 min with 90% methanol. The method finally concluded with Step 4 to achieve initial concentration of methanol that is, 35% thus contributing the total method run time of 17.5 min. The flow rate was 0.25 mL/min throughout the process. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity, and recovery. The method was linear and found to be acceptable over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study of ATSV + OLM in combination against OLM treatment on blood pressure by quantifying changes in levels of ALD in hypertensive patients. The study revealed levels of ALD were significantly higher in ATSV + OLM treatment condition when compared to OLM as single treated condition. This reflects the reason of low effectiveness of ATSV + OLM in combination instead of synergistic activity.

  17. Treatment Combining X-Irradiation and a Ribonucleoside Anticancer Drug, TAS106, Effectively Suppresses the Growth of Tumor Cells Transplanted in Mice

    International Nuclear Information System (INIS)

    Purpose: To examine the in vivo antitumor efficacy of X-irradiation combined with administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-β-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. Methods and Materials: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe combined immunodeficient mice, respectively. They were treated with a relatively low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5 mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5 to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for proliferative and apoptotic cells in the tumors were performed using Ki-67 immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end labeling staining. The expression of survivin, a key molecule related to tumor survival, was assessed by quantitative polymerase chain reaction and immunohistochemical analysis. Results: When X-irradiation and TAS106 treatment were combined, significant inhibition of tumor growth was observed in both types of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked inhibition of tumor growth was observed in half of the mice that received the combined treatment three times at 2-day intervals. Parallel to these phenomena, the suppression of survivin expression and appearance of Ki-67-negative and apoptotic cells were observed. Conclusions: X-irradiation and TAS106 effectively suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is thought to mainly contribute to the suppression of the tumor growth

  18. A quantitative benefit-risk assessment approach to improve decision making in drug development: Application of a multicriteria decision analysis model in the development of combination therapy for overactive bladder.

    Science.gov (United States)

    de Greef-van der Sandt, I; Newgreen, D; Schaddelee, M; Dorrepaal, C; Martina, R; Ridder, A; van Maanen, R

    2016-04-01

    A multicriteria decision analysis (MCDA) approach was developed and used to estimate the benefit-risk of solifenacin and mirabegron and their combination in the treatment of overactive bladder (OAB). The objectives were 1) to develop an MCDA tool to compare drug effects in OAB quantitatively, 2) to establish transparency in the evaluation of the benefit-risk profile of various dose combinations, and 3) to quantify the added value of combination use compared to monotherapies. The MCDA model was developed using efficacy, safety, and tolerability attributes and the results of a phase II factorial design combination study were evaluated. Combinations of solifenacin 5 mg and mirabegron 25 mg and mirabegron 50 (5+25 and 5+50) scored the highest clinical utility and supported combination therapy development of solifenacin and mirabegron for phase III clinical development at these dose regimens. This case study underlines the benefit of using a quantitative approach in clinical drug development programs. PMID:26422298

  19. Effects of antihypertensive drugs losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension combined with isolated impaired fasting glucose.

    Science.gov (United States)

    Xiao, Wei-Yin; Ning, Ning; Tan, Ming-Hong; Jiang, Xue-Shu; Zhou, Liang; Liu, Ling; Yi, Dong; Wei, Ping

    2016-05-01

    The objective of this study was to observe the antihypertensive effect of losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension (EH) combined with isolated impaired fasting glucose (i-IFG). Patients (n=244) were randomly assigned to losartan potassium tablets (50-100 mg per day) or levamlodipine besylate tablets (2.5-5.0 mg per day) for intensive antihypertensive treatment with no lifestyle interventions for 3 years. The changes in fasting plasma glucose, fasting insulin (FINS) and insulin sensitivity index (ISI) from before to after treatment were observed. Blood pressure (BP) in each group was significantly reduced by treatment (P0.05). The incidence of new-onset diabetes mellitus was not significantly different between two groups. The antihypertensive effect of losartan and levamlodipine besylate could amoliorate insulin resistance in patients with EH combined with i-IFG. The improvement of insulin resistance by losartan potassium at 12 months might be better than that by levamlodipine besylate; however, after 24 and 36 months of follow-up, both agents significantly alleviated insulin resistance. These results suggest that the effects of these two drugs on insulin resistance are not significantly different. PMID:26763851

  20. The efficacy and tolerability of the slow-acting combined agent glucosamine and chondroitin sulfate in gonarthrosis patients tacking no nonsteroidal anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    A. P. Rebrov

    2015-01-01

    Full Text Available Objective: to evaluate the efficacy and tolerability of the combined symptomatic slow-acting combined agent Theraflex in gonarthrosis patients untreated with nonsteroidal antiinflammatory drugs (NSAIDs.Patients and methods. The investigation enrolled 84 patients (78 women and 6 men aged 55.23±7.36 years with knee arthritis lasting 6.2±0.98 years who were blindly randomized into 2 groups. A study group took Theraflex (chondroitin sulfate 400 mg and glucosamine sulfate 500 mg with or without acetaminophen. A comparison group received acetaminophen only. At baseline and 3 and 6 months after treatment, the investigators assessed changes in the magnitude of osteoarthritis (OA using WOMAC and Lequen's indices, evaluated the therapeutic efficiency rated by a patient and a physician according to the visual analogue scale, and took into account adverse reactions (AR.Results. All the patients taking Theraflex for 6 months showed a positive effect in substantially lowering WOMAC and Lequen's indices and reducing pain and needs for analgesics as compared to both the values at baseline and those obtained in the patients receiving acetaminophen only.Conclusion. In osteoarthritis patients untreated with NSAIDs, Theraflex treatment was associated with a reduction in pain syndrome and stiffness and with better function and lower needs for analgesics. Six-month Theraflex therapy did not cause serious ARs, as well as in patients having controlled gastrointestinal and renal diseases and hypertension

  1. A micro fluidic system to study the cytotoxic effect of drugs: the combined effect of celecoxib and 5-fluorouracil on normal and cancer cells

    International Nuclear Information System (INIS)

    We have investigated the response of normal and cancer cells to exposure a combination of celecoxib (Celbx) and 5-fluorouracil (5-FU) using a lab-on-a-chip micro fluidic device. Specifically, we have tested the cytotoxic effect of Celbx on normal mouse embryo cells (Balb/c 3T3) and human lung carcinoma cells (A549). The single drugs or their combinations were adjusted to five different concentrations using a concentration gradient generator (CGG) in a single step. The results suggest that Celbx can enhanced the anticancer activity of 5-FU by stronger inhibition of cancer cell growth. We also show that the A549 cancer cells are more sensitive to Celbx than the Balb/c 3T3 normal cells. The results obtained with the micro fluidic system were compared to those obtained with a macro scale in vitro cell culture method. In our opinion, the micro fluidic system represents a unique approach for an evaluation of cellular response to multidrug exposure that also is more simple than respective micro well plate assays. (author)

  2. Clinical Study of Drug-resistant Pulmonary Tuberculosis Treated by Combination of Anti-Tuberculosis Chemicals and Compound Astragalus Capsule(复方黄芪胶囊)

    Institute of Scientific and Technical Information of China (English)

    姜艳; 李新; 于志勇; 尹红义; 韩玉庆

    2004-01-01

    Objective: To observe and evaluate the therapeutic effect of anti-tuberculosis (anti-TB) chemicals and Compound Astragalus Capsule (CAC) in combinedly treating drug resistant pulmonary tuberculosis (DR-TB). Methods: Ninety-two patients with DR-TB were equally randomized into the treated group (treated with combination therapy) and the control group (treated with anti-TB chemicals alone). The therapeutic course for both groups was 18 months. Therapeutic effects between the two groups were compared at the end of the therapeutic course. Sputum bacterial negative rate, focal absorption effective rate, cavity closing rate, 10-day symptom improving rate, the incidence of adverse reaction and 2-year bacteriological recurrence rate between the two groups were compared. Results: In the treated group, the sputum bacterial negative conversion rate was 84. 8%, focal absorption effective rate 91.3 %, cavity closing rate 58. 7 % and 10-day symptom improving rate 54.4%, while in the control group, the corresponding rates were 65.2%,73.9 %, 37. 0% and 26.1%, respectively. Comparison between the groups showed significant difference in all the parameters ( P<0.05, P<0.05, P<0.05 and P<0.01 ). The incidence of adverse reaction and 2year bacteriological recurrence rate in the treated group were 23.9 % and 2.6 % respectively, while those in the control group 50.0% and 16.7%, which were higher than the former group with significant difference ( P<0.01 and P<0.05, respectively). Conclusion: The therapeutic effect of combined treatment with antiTB and CAC is superior to that of treatment with anti-TB chemicals alone, and the Chinese herbal medicine showed an adverse reaction alleviating effect, which provides a new therapy for DR-TB, and therefore, it is worth spreading in clinical practice.

  3. Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

    Science.gov (United States)

    Maurer, Verena; Murphy, Conor; Schmuckermair, Claudia; Muigg, Patrick; Neumann, Inga D.; Whittle, Nigel

    2016-01-01

    Background: Despite its success in treating specific anxiety disorders, the effect of exposure therapy is limited by problems with tolerability, treatment resistance, and fear relapse after initial response. The identification of novel drug targets facilitating fear extinction in clinically relevant animal models may guide improved treatment strategies for these disorders in terms of efficacy, acceleration of fear extinction, and return of fear. Methods: The extinction-facilitating potential of neuropeptide S, D-cycloserine, and a benzodiazepine was investigated in extinction-impaired high anxiety HAB rats and 129S1/SvImJ mice using a classical cued fear conditioning paradigm followed by extinction training and several extinction test sessions to study fear relapse. Results: Administration of D-cycloserine improved fear extinction in extinction-limited, but not in extinction-deficient, rodents compared with controls. Preextinction neuropeptide S caused attenuated fear responses in extinction-deficient 129S1/SvImJ mice at extinction training onset and further reduced freezing during this session. While the positive effects of either D-cycloserine or neuropeptide S were not persistent in 129S1/SvImJ mice after 10 days, the combination of preextinction neuropeptide S with postextinction D-cycloserine rendered the extinction memory persistent and context independent up to 5 weeks after extinction training. This dual pharmacological adjunct to extinction learning also protected against fear reinstatement in 129S1/SvImJ mice. Conclusions: By using the potentially nonsedative anxiolytic neuropeptide S and the cognitive enhancer D-cycloserine to facilitate deficient fear extinction, we provide here the first evidence of a purported efficacy of a dual over a single drug approach. This approach may render exposure sessions less aversive and more efficacious for patients, leading to enhanced protection from fear relapse in the long term. PMID:26625894

  4. Study on Combined Use of Drugs of Radix Achyranthis Bidentatae and Flos cartham%牛膝与红花配伍的实验研究

    Institute of Scientific and Technical Information of China (English)

    陈辉; 毛晓健; 毛小平; 肖庆慈; 刘维英

    2001-01-01

    观察研究牛膝与红花配伍前后对血液、抗炎、免疫器官重量等指标的影响。结果表明:牛膝、红花均能降低RBC数、Hb含量,延长凝血时间,增大毛细血管的直径和开放数,有抗炎作用,能明显升高脾脏指数,合用后以上作用均较单用增强,各给药组对胸腺影响不明显,合剂组能降低肾上腺指数,为二者相须为用能增强活血化瘀之功的理论,提供了一定的科学依据。%The effects of combined use of drugs of Padix Achyranthis Bidentatae and Flos carthami on blood,anti - inflammatory and the weight of immune organ and so on have heen observed. The result shows that Radix Achyranthis Bidentatae and Flos carthami can decrease numbers of RBC and Hb, blood coagulation time can be delayed. Thediameter and open number of capillary is increased. It is also anti- infammatory and can enhance spleen index. Thecombination of the two is more effective than each used alone, which furnish a science evidence for mutual promotion ofthe two drugs and activating blood circulation to dissipate blood stasis.

  5. A combined liquid chromatography-triple-quadrupole mass spectrometry method for the residual detection of veterinary drugs in porcine muscle, milk, and eggs.

    Science.gov (United States)

    Zhang, Dan; Park, Zee-Yong; Park, Jin-A; Kim, Seong-Kwan; Jeong, Daun; Cho, Sang-Hyun; Shim, Jae-Han; Kim, Jin-Suk; Abd El-Aty, A M; Shin, Ho-Chul

    2016-06-01

    A liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed for monitoring and detection of four different drugs, namely acetanilide, pentylenetetrazole, phenacetin, and tetramethrin in porcine muscle, pasteurized milk, and table egg samples. For acetanilide and pentylenetetrazole, the samples were extracted with 0.1 % formic acid in acetonitrile, followed by defatting with n-hexane, partitioning at -20 °C for 1 h, centrifugation, and filtration, whereas the quick, easy, cheap, effective, rugged, and safe "QuEChERS" method was used for phenacetin and tetramethrin. The final extracts were combined and analyzed in a single chromatographic run using an XBridge(TM) analytical column and 0.1 % formic acid and 10 mM ammonium formate in ultrapure water (A) and 0.1 % formic acid and 10 mM ammonium formate in methanol (B) as the mobile phase. Owing to the unavailability of internal standards, matrix-matched calibrations were used for analyte quantification with coefficients of determination (R (2)) ≥ 0.9865. The intra- and inter-day accuracies ranged from 60.75 to 90.90 % and from 63.75 to 89.30 %, respectively, while the respective analytical precisions were 1.48-17.44 % (23.3 % for porcine sample spiked with phenacetin) and 1.97-15.78 %. The limits of quantification (LOQ) were between 0.5 and 2.5 ng/g in the matrices tested. Food samples purchased from local markets in Seoul were analyzed using the developed method and none of the tested drugs was detected. PMID:27178050

  6. Cost-Effectiveness of Combined Sexual and Injection Risk Reduction Interventions among Female Sex Workers Who Inject Drugs in Two Very Distinct Mexican Border Cities.

    Directory of Open Access Journals (Sweden)

    Jose L Burgos

    Full Text Available We evaluated the cost-effectiveness of combined single session brief behavioral intervention, either didactic or interactive (Mujer Mas Segura, MMS to promote safer-sex and safer-injection practices among female sex workers who inject drugs (FSW-IDUs in Tijuana (TJ and Ciudad-Juarez (CJ Mexico. Data for this analysis was obtained from a factorial RCT in 2008-2010 coinciding with expansion of needle exchange programs (NEP in TJ, but not in CJ.A Markov model was developed to estimate the incremental cost per quality adjusted life year gained (QALY over a lifetime time frame among a hypothetical cohort of 1,000 FSW-IDUs comparing a less intensive didactic vs. a more intensive interactive format of the MMS, separately for safer sex and safer injection combined behavioral interventions. The costs for antiretroviral therapy was not included in the model. We applied a societal perspective, a discount rate of 3% per year and currency adjusted to US$2014. A multivariate sensitivity analysis was performed. The combined and individual components of the MMS interactive behavioral intervention were compared with the didactic formats by calculating the incremental cost-effectiveness ratios (ICER, defined as incremental unit of cost per additional health benefit (e.g., HIV/STI cases averted, QALYs compared to the next least costly strategy. Following guidelines from the World Health Organization, a combined strategy was considered highly cost-effective if the incremental cost per QALY gained fell below the gross domestic product per capita (GDP in Mexico (equivalent to US$10,300.For CJ, the mixed intervention approach of interactive safer sex/didactic safer injection had an incremental cost-effectiveness ratio (ICER of US$4,360 ($310-$7,200 per QALY gained compared with a dually didactic strategy. Using the dually interactive strategy had an ICER of US$5,874 ($310-$7,200 compared with the mixed approach. For TJ, the combination of interactive safer sex

  7. Chinese patent medicine liu wei di huang wan combined with antihypertensive drugs, a new integrative medicine therapy, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Wang, Jie; Yao, Kuiwu; Yang, Xiaochen; Liu, Wei; Feng, Bo; Ma, Jizheng; Du, Xinliang; Wang, Pengqian; Xiong, Xingjiang

    2012-01-01

    Objectives. To assess the beneficial and adverse effects of Liu Wei Di Huang Wan (LWDHW), combined with antihypertensive drugs, for essential hypertension. Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of LWDHW combined with antihypertensive drugs for essential hypertension reported in any language, with main outcome measures as blood pressure. The quality of the included studies was assessed with the Jadad scale and a customized standard quality assessment scale. Results. 6 randomized trials were included. The methodological quality of the trials was evaluated as generally low. The pooled results showed that LWDHW combined with antihypertensive drugs was more effective in blood pressure and the scale for TCM syndrome and symptom differentiation scores compared with antihypertensive drugs alone. Most of the trials did not report adverse events, and the safety is still uncertain. Conclusions. LWDHW combined with antihypertensive drugs appears to be effective in improving blood pressure and symptoms in patients with essential hypertension. However, the evidence remains weak due to the poor methodological quality of the included studies. PMID:23258998

  8. Chinese Patent Medicine Liu Wei Di Huang Wan Combined with Antihypertensive Drugs, a New Integrative Medicine Therapy, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    Jie Wang

    2012-01-01

    Full Text Available Objectives. To assess the beneficial and adverse effects of Liu Wei Di Huang Wan (LWDHW, combined with antihypertensive drugs, for essential hypertension. Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of LWDHW combined with antihypertensive drugs for essential hypertension reported in any language, with main outcome measures as blood pressure. The quality of the included studies was assessed with the Jadad scale and a customized standard quality assessment scale. Results. 6 randomized trials were included. The methodological quality of the trials was evaluated as generally low. The pooled results showed that LWDHW combined with antihypertensive drugs was more effective in blood pressure and the scale for TCM syndrome and symptom differentiation scores compared with antihypertensive drugs alone. Most of the trials did not report adverse events, and the safety is still uncertain. Conclusions. LWDHW combined with antihypertensive drugs appears to be effective in improving blood pressure and symptoms in patients with essential hypertension. However, the evidence remains weak due to the poor methodological quality of the included studies.

  9. Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Young Ki Lee

    2013-12-01

    Full Text Available BackgroundThis study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D.MethodsThis prospective observational study was conducted across 24 weeks for drug-naïve Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin. Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%≤HbA1c<9.0%; category II, 9.0%≤HbA1c<11.0%; category III, 11.0%≤HbA1c.ResultsAmong 116 subjects, 99 subjects completed the study, with 88 subjects maintaining the initial medication. While each of the metformin-based dual therapies showed a significant decrease in HbA1c (group 1, 8.9% to 6.4%; group 2, 9.0% to 6.6%; group 3, 9.3% to 6.3%; P<0.001 for each, there was no significant difference in the magnitude of HbA1c change among the groups. While the three HbA1c categories showed significantly different baseline HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001, endpoint HbA1c was not different (6.4% vs. 6.6% vs. 6.0%; P=0.051.ConclusionThe three dual therapies using a combination of metformin and either sulfonylurea, pioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naïve Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels.

  10. Effect of intracapsular steroid injection in combination with arthrocentesis followed by mouth opening exercises and nonsteroidal anti-inflammatory drug treatment for closed lock

    International Nuclear Information System (INIS)

    Recent biochemical studies of synovial fluids indicate that temporomandibular joint (TMJ) symptoms are caused by intra-articular inflammation. There are various ways to manage such disorders. Arthrocentesis is one effective treatment for closed lock. The aim of this study was to evaluate the efficacy of arthrocentesis (steroid injection) followed by mouth opening exercises during non-steroidal anti-inflammatory drug (NSAID) therapy as a primary treatment for closed lock. The ultimate goal was to increase the improvement rate and the number of patients with no TMJ dysfunction. Subjects were selected from a series of patients with newly diagnosed closed lock who presented at Aichi-Gakuin University Hospital between January 2003 and December 2004. Sixty-two patients were confirmed to have closed lock with MRI. The patients underwent two consecutive sessions of arthrocentesis at a 2 week interval and were followed up every 2 weeks for 12 weeks. NSAID administration and mouth opening exercises were performed daily until the patient's symptoms improved. The improvement rate was calculated as the percentage of improved cases among the total number of cases in each group. The improvement rates were 27%, 43%, 56%, 62%, 65%, and 71% after 2, 4, 6, 8, 10, and 12 weeks, respectively. Improvement to a TMJ classification of no dysfunction was achieved in 11% of the patients. This combination therapy (steroid injection) is an effective primary treatment because the improvement rate was as higher as 71%, and 11% of all patients had improved to a TMJ classification of no dysfunction. (author)

  11. Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis

    International Nuclear Information System (INIS)

    Single drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated. PC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin α and β subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined. All drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin α and β subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination. Simultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer

  12. Liquid-liquid extraction combined with high performance liquid chromatography-diode array-ultra-violet for simultaneous determination of antineoplastic drugs in plasma

    Directory of Open Access Journals (Sweden)

    Ananda Lima Sanson

    2011-06-01

    Full Text Available A liquid-liquid extraction (LLE combined with high-performance liquid chromatography-diode array detection method for simultaneous analysis of four chemically and structurally different antineoplastic drugs (cyclophosphamide, doxorubicin, 5-fluorouracil and ifosfamide was developed. The assay was performed by isocratic elution, with a C18 column (5 µm, 250 x 4.6 mm and mobile phase constituted by water pH 4.0- acetonitrile-methanol (68:19:13, v/v/v, which allowed satisfactory separation of the compounds of interest. LLE, with ethyl acetate, was used for sample clean-up with recoveries ranging from 60 to 98%. The linear ranges were from 0.5 to 100 µg mL-1, for doxorubicin and 1 to 100 µg mL-1, for the other compounds. The relative standard deviations ranged from 5.5 to 17.7%. This method is a fast and simple alternative that can be used, simultaneously, for the determination of the four drugs in plasma, with a range enabling quantification of the drugs in pharmacokinetics, bioequivalence and therapeutic drug-monitoring studies.Um método de extração líquido-líquido (ELL combinado com cromatografia líquida de alta eficiência-detector de arranjo de diodos foi desenvolvido para análise simultânea de quatro fármacos antineoplásicos quimicamente e estruturalmente diferentes (ciclofosfamida, doxorrubicina, fluoruracila e ifosfamida. O estudo foi realizado sob condições isocráticas, com coluna C18 (5µm, 250 x 4.6 mm e fase móvel constituída por água pH 4.0-acetonitrila-metanol (68:19:13, v/v/v, que permitiu separação satisfatória dos analitos de interesse. A ELL, com acetato de etila, foi utilizada para limpeza da amostra, com recuperação variando de 60 a 98%. As faixas foram lineares de 0,5 a 100 µg mL-1 para doxorrubicina e 1 a 100 µg mL-1 para os outros compostos. O desvio padrão relativo variou de 5,5 a 17,7%. Este método é uma alternativa rápida e simples que pode ser usado, simultaneamente, para a determinação dos

  13. Mujer Mas Segura (Safer Women: a combination prevention intervention to reduce sexual and injection risks among female sex workers who inject drugs

    Directory of Open Access Journals (Sweden)

    Vera Alicia

    2012-08-01

    Full Text Available Abstract Background Female sex workers who inject drugs (FSW-IDUs are at risk of acquiring HIV, sexually transmitted infections (STI and blood-borne infections through unprotected sex and sharing injection equipment. We conducted a 2×2 factorial randomized controlled trial to evaluate combination interventions to simultaneously reduce sexual and injection risks among FSW-IDUs in Tijuana and Ciudad Juarez, Mexico. Methods/design FSW-IDUs ≥18 years reporting sharing injection equipment and unprotected sex with clients within the last month were randomized to one of four conditions based on an a priori randomization schedule, blinding interviewer/counselors to assignment. Due to the extreme vulnerability of this population, we did not include a control group that would deny some women access to preventive information. All women received similar information regardless of group allocation; the difference was in the way the information was delivered and the extent to which women had an interactive role. Each condition was a single 60-minute session, including either an interactive or didactic version of an injection risk intervention and sexual risk intervention. Women underwent interviewer-administered surveys and testing for HIV, syphilis, gonorrhea, Chlamydia, and Trichomonas at baseline and quarterly for 12 months. Combined HIV/STI incidence will be the primary outcome. Secondary outcomes are proportionate reductions in sharing of injection equipment and unprotected sex with clients. Discussion Of 1,132 women, 548 (48.4% were excluded (88.9% were ineligible; 11.1% refused to participate or did not return; 584 eligible women enrolled (284 in Tijuana; 300 in Ciudad Juarez. All 584 participants completed the baseline interview, provided biological samples and were randomized to one of the four groups. During follow-up, 17 participants (2.9% were lost to follow-up, of whom 10 (58.8% had died, leaving 567 participants for analysis. This study

  14. Novel management strategy for coronary steal syndrome: case report of occlusion of a LIMA graft side branch with a combination of drug-eluting and covered-stent deployment.

    LENUS (Irish Health Repository)

    Hynes, Brian G

    2009-11-01

    We report a novel percutaneous therapeutic approach to the management of suspected coronary artery steal syndrome resulting from a large side branch of the left internal mammary artery bypass graft, using a combination of coated and drug-eluting stents. We demonstrate the feasibility and long-term efficacy of this strategy in a case report.

  15. A Targeted DNAzyme-Nanocomposite Probe Equipped with Built-in Zn2+ Arsenal for Combined Treatment of Gene Regulation and Drug Delivery

    OpenAIRE

    Zhi-Mei He; Peng-Hui Zhang; Xin Li; Jian-Rong Zhang; Jun-Jie Zhu

    2016-01-01

    As catalytic nucleic acids, DNAzymes have been extensively used in the design of sensing platforms. However, their potentials as intelligent drug carriers for responsive drug release in gene therapy and chemotherapy were rarely explored. Herein, we report a dual-functional probe composed of gold nanoparticles (GNPs), catalytic Zn2+-dependent DNAzyme, anticancer drug doxorubicin (Dox), targeted AS1411 aptamer and acid-decomposable ZnO quantum dots (ZnO QDs) to achieve intracellular gene regula...

  16. Drugs Approved for Bladder Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bladder cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  17. Drugs Approved for Breast Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for breast cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  18. Molecular monitoring of plasmodium falciparum drug susceptibility at the time of the introduction of artemisinin-based combination therapy in Yaoundé, Cameroon: Implications for the future

    Directory of Open Access Journals (Sweden)

    Menard Sandie

    2012-04-01

    Full Text Available Abstract Background Regular monitoring of the levels of anti-malarial resistance of Plasmodium falciparum is an essential policy to adapt therapy and improve malaria control. This monitoring can be facilitated by using molecular tools, which are easier to implement than the classical determination of the resistance phenotype. In Cameroon, chloroquine (CQ, previously the first-line therapy for uncomplicated malaria was officially withdrawn in 2002 and replaced initially by amodiaquine (AQ monotherapy. Then, artemisinin-based combination therapy (ACT, notably artesunate-amodiaquine (AS-AQ or artemether-lumefantrine (AL, was gradually introduced in 2004. This situation raised the question of the evolution of P. falciparum resistance molecular markers in Yaoundé, a highly urbanized Cameroonian city. Methods The genotype of pfcrt 72 and 76 and pfmdr1 86 alleles and pfmdr1 copy number were determined using real-time PCR in 447 P. falciparum samples collected between 2005 and 2009. Results This study showed a high prevalence of parasites with mutant pfcrt 76 (83% and pfmdr1 86 (93% codons. On the contrary, no mutations in the pfcrt 72 codon and no samples with duplication of the pfmdr1 gene were observed. Conclusion The high prevalence of mutant pfcrt 76T and pfmdr1 86Y alleles might be due to the choice of alternative drugs (AQ and AS-AQ known to select such genotypes. Mutant pfcrt 72 codon was not detected despite the prolonged use of AQ either as monotherapy or combined with artesunate. The absence of pfmdr1 multicopies suggests that AL would still remain efficient. The limited use of mefloquine or the predominance of mutant pfmdr1 86Y codon could explain the lack of pfmdr1 amplification. Indeed, this mutant codon is rarely associated with duplication of pfmdr1 gene. In Cameroon, the changes of therapeutic strategies and the simultaneous use of several formulations of ACT or other anti-malarials that are not officially recommended result in a

  19. The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites.

    Science.gov (United States)

    Staack, Roland F; Varesio, Emmanuel; Hopfgartner, Gérard

    2005-01-01

    An approach has been developed for drug metabolism studies of non-radiolabeled compounds using on-line liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with chip-based infusion following fraction collection. The potential of this approach, which improves the data quality compared with only LC/MS analysis, has been investigated for the analysis of in vitro metabolites of tolcapone and talinolol, two compounds with well-characterized metabolism. The information-dependent LC/MS/MS analysis enables the characterization of the major metabolites while the chip-based infusion is used to obtain good product ion spectra for lower level metabolites, to generate complementary MS information on potential metabolites detected in the LC/MS trace, or to screen for unexpected metabolites. Fractions from the chromatographic analysis are collected in 20 second steps, into a 96-well plate. The fractions of interest can be re-analyzed with chip-based infusion on a variety of mass spectrometers including triple quadrupole linear ion trap (QqLIT or Q TRAP) and QqTOF systems. Acquiring data for several minutes using multi-channel acquisition (MCA), or signal averaging while infusing the fractions at approximately 200 nL/min, permits about a 50 times gain in sensitivity (signal-to-noise) in MS/MS mode. A 5-10 microL sample fraction can be infused for more than 30 min allowing the time to perform various MS experiments such as MS(n), precursor ion or neutral loss scans and accurate mass measurement, all in either positive or negative mode. Through fraction collection and infusion, a significant gain in data quality is obtained along with a time-saving benefit, because the original sample needs neither to be re-analyzed by re-injection nor to be pre-concentrated. Therefore, a novel hydroxylated talinolol metabolite could be characterized with only one injection. PMID:15685686

  20. Nucleolin overexpression in breast cancer cell sub-populations with different stem-like phenotype enables targeted intracellular delivery of synergistic drug combination.

    Science.gov (United States)

    Fonseca, Nuno A; Rodrigues, Ana S; Rodrigues-Santos, Paulo; Alves, Vera; Gregório, Ana C; Valério-Fernandes, Ângela; Gomes-da-Silva, Lígia C; Rosa, Manuel Santos; Moura, Vera; Ramalho-Santos, João; Simões, Sérgio; Moreira, João Nuno

    2015-11-01

    Breast cancer stem cells (CSC) are thought responsible for tumor growth and relapse, metastization and active evasion to standard chemotherapy. The recognition that CSC may originate from non-stem cancer cells (non-SCC) through plastic epithelial-to-mesenchymal transition turned these into relevant cell targets. Of crucial importance for successful therapeutic intervention is the identification of surface receptors overexpressed in both CSC and non-SCC. Cell surface nucleolin has been described as overexpressed in cancer cells as well as a tumor angiogenic marker. Herein we have addressed the questions on whether nucleolin was a common receptor among breast CSC and non-SCC and whether it could be exploited for targeting purposes. Liposomes functionalized with the nucleolin-binding F3 peptide, targeted simultaneously, nucleolin-overexpressing putative breast CSC and non-SCC, which was paralleled by OCT4 and NANOG mRNA levels in cells from triple negative breast cancer (TNBC) origin. In murine embryonic stem cells, both nucleolin mRNA levels and F3 peptide-targeted liposomes cellular association were dependent on the stemness status. An in vivo tumorigenic assay suggested that surface nucleolin overexpression per se, could be associated with the identification of highly tumorigenic TNBC cells. This proposed link between nucleolin expression and the stem-like phenotype in TNBC, enabled 100% cell death mediated by F3 peptide-targeted synergistic drug combination, suggesting the potential to abrogate the plasticity and adaptability associated with CSC and non-SCC. Ultimately, nucleolin-specific therapeutic tools capable of simultaneous debulk multiple cellular compartments of the tumor microenvironment may pave the way towards a specific treatment for TNBC patient care. PMID:26283155

  1. Antiretroviral drugs.

    Science.gov (United States)

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one. PMID:20471318

  2. 拼合原理在降压新药研发中的应用构想%Combination Principles and Their Application in the Research and Development of New Antihypertensive Drugs

    Institute of Scientific and Technical Information of China (English)

    王忠雷; 张小华; 杨丽燕; 曾祥伟; 李朋收; 潘激扬; 袁建娜; 杨珍

    2013-01-01

    Hypertension, as a primary dangerous factor of cardiovascular and cerebrovascular diseases, has become a heavy burden to the family and country. Due to complicated aetiological agent and unclear pathogenesis, the treatment and management of hypertension have become an urgent need in the clinical practice. In recent years, people have realized that if they want to achieve the desired antihypertensive effect, drug combination becomes an inevitable choice. If we use combination principles which assembling two basic structures of anti-hypertension drug in one molecule, we will obtain the new antihypertensive drugs with decreased toxic side effects and increased pharmacological effect .This application will not only open up a new way for drug combination, but also reflect a new development trends of drug combination.%因高血压发病机制较为复杂、发病机理不甚明确等,导致对其治疗和控制已成为当今临床迫切需要解决的难题.近年来,人们已逐步认识到要想达到理想的降压效果,联合用药已成为必然选择.若利用拼合原理,将两个降压药物的基本结构拼合在一个分子中,有望获得毒副作用小、药理效应相加的降压新药.该应用构想不仅可为联合用药开辟一条新的途径,也可体现联合用药新的发展趋势.

  3. Combined hERG channel inhibition and disruption of trafficking in drug-induced long QT syndrome by fluoxetine: a case-study in cardiac safety pharmacology

    OpenAIRE

    Hancox, J. C.; Mitcheson, J S

    2006-01-01

    Drug-induced prolongation of the rate-corrected QT interval (QTCI) on the electrocardiogram occurs as an unwanted effect of diverse clinical and investigational drugs and carries a risk of potentially fatal cardiac arrhythmias. hERG (human ether-à-go-go-related gene) is the gene encoding the α-subunit of channels mediating the rapid delayed rectifier K+ current, which plays a vital role in repolarising the ventricles of the heart. Most QTCI prolonging drugs can inhibit the function of recombi...

  4. Drugs Approved for Multiple Myeloma

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for multiple myeloma and other plasma cell neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  5. Drugs Approved for Cervical Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for cervical cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  6. Drugs Approved for Testicular Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for testicular cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  7. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental ...

  9. Comparison of Boric Acid and Combination Drug of Polymyxin, Neomycin and Hydrocortisone (polymyxin NH) in the Treatment of Acute Otitis Externa

    Science.gov (United States)

    Moeini, Mohammad

    2016-01-01

    Introduction Acute otitis externa is an inflammation of the external auditory canal known as "swimmer’s ear". Direct costs including medical treatment, painkillers, antibiotics, steroids or both and indirect costs are also remarkable. Aim The aim of this study was to compare the effect of boric acid and polymyxin, neomycin and hydrocortisone composition in the treatment of acute otitis externa. Materials and Methods This randomized clinical trial was carried out on 80 patients aged more than 17-year-old who were referred to Kashani hospital clinic with a diagnosis of acute otitis externa by otolaryngologist. The patients were randomly allocated to two groups (A: Boric acid and B: polymyxin NH ear drops) and Painkiller was prescribed and administered orally for all patients and in the presence of fever, cellulitis around the ears and neck adenopathy, broad-spectrum systemic antibiotics were used besides topical treatment. Symptoms of patients who were evaluated by a physician includes pain, discharge from the ear, swelling of the ear canal, auricle swelling, tenderness, and ear itching. In addition, pain was evaluated in patients and was recorded by Macgill Pain Questionnaire, in the first, third, seventh and tenth days. Results Results showed that itching on third day (p=0.007) and swelling of the ear canal in the examination of the third day (p=0.006) and the seventh day (p=0.001) in the polymyxin NH group was more than those of boric acid group. Overall mean pain based on McGill questionnaire was 11.10±1.49 in boric acid group in the examination on the first day and was 4.05±0.22 in the examination on the tenth day and in the polymyxin NH group, it was 10.9±0.99 on the first day and 4.20±0.40 on the tenth day. In both groups, pain relief was the same and there was no significant difference between two groups (p=0.075). Conclusion The findings of this study showed slight differences in the effectiveness of the boric acid drug and combination of polymyxin

  10. Combined anti-inflammatory and anti-AGE drug treatments have a protective effect on intervertebral discs in mice with diabetes.

    Directory of Open Access Journals (Sweden)

    Svenja Illien-Junger

    Full Text Available OBJECTIVE: Diabetes and low back pain are debilitating diseases and modern epidemics. Diabetes and obesity are also highly correlated with intervertebral disc (IVD degeneration and back pain. Advanced-glycation-end-products (AGEs increase reactive-oxygen-species (ROS and inflammation, and are one cause for early development of diabetes mellitus. We hypothesize that diabetes results in accumulation of AGEs in spines and associated spinal pathology via increased catabolism. We present a mouse model showing that: 1 diabetes induces pathological changes to structure and composition of IVDs and vertebrae; 2 diabetes is associated with accumulation of AGEs, TNFα, and increased catabolism spinal structures; and 3 oral-treatments with a combination of anti-inflammatory and anti-AGE drugs mitigate these diabetes-induced degenerative changes to the spine. METHODS: Three age-matched groups of ROP-Os mice were compared: non-diabetic, diabetic (streptozotocin (STZ-induced, or diabetic mice treated with pentosan-polysulfate (anti-inflammatory and pyridoxamine (AGE-inhibitor. Mice were euthanized and vertebra-IVD segments were analyzed by μCT, histology and Immunohistochemistry. RESULTS: Diabetic mice exhibited several pathological changes including loss in IVD height, decreased vertebral bone mass, decreased glycosaminoglycan content and morphologically altered IVDs with focal deposition of tissues highly expressing TNFα, MMP-13 and ADAMTS-5. Accumulation of larger amounts of methylglyoxal suggested that AGE accumulation was associated with these diabetic degenerative changes. However, treatment prevented or reduced these pathological effects on vertebrae and IVD. CONCLUSION: This is the first study to demonstrate specific degenerative changes to nucleus pulposus (NP morphology and their association with AGE accumulation in a diabetic mouse model. Furthermore, this is the first study to demonstrate that oral-treatments can inhibit AGE-induced ROS and

  11. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony;

    2013-01-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years...... contingent valuation survey among drug shop customers in Mukono District, Uganda. Exit interviews were undertaken with customers aged 15 years and above after leaving a drug shop having purchased an antimalarial and/or paracetamol. The bidding game technique was used to elicit the willingness-to-pay (WTP...... RDT. Factors strongly associated with a higher WTP for these commodities included having a higher socio-economic status, no fever/malaria in the household in the past 2 weeks and if a malaria diagnosis had been obtained from a qualified health worker prior to visiting the drug shop. The findings...

  12. Recreational Drug Use among Chinese Men Who Have Sex with Men: A Risky Combination with Unprotected Sex for Acquiring HIV Infection

    Directory of Open Access Journals (Sweden)

    Jun-Jie Xu

    2014-01-01

    Full Text Available Objective. To investigate the prevalence of recreational drug use and its relationship with HIV infection among Chinese MSM. Methods. A cross-sectional study of 625 MSM was conducted in Shenyang, China. Questionnaires were administered to collect information on recreational drug use and sexual behaviors. Blood specimens were collected to test for HIV and syphilis antibodies. Results. Nearly a quarter (23.2%, 145/625 of participants reported ever using recreational drugs, among which alkyl nitrites (poppers was the most frequently used drug (19.2%, followed by methylmorphine phosphate (5.1%, methamphetamine (4.0%, and ketamine (0.8%. The overall prevalence of HIV and syphilis was 9.6% and 10.4%, respectively. Multivariate logistic analysis showed that recreational drug use was significantly correlated with age ≤25 year (adjusted odds ratio [aOR] = 1.6, 95% CI, 1.1–2.9, single marital status (aOR = 2.1, 95% CI, 1.2–3.6, and seeking male sexual partners mainly through Internet (aOR = 1.8, 95% CI, 1.8–2.8. Recreational drug use was independently associated with an increased risk of HIV infection (aOR = 3.5, 95% CI, 2.0–6.2. Conclusions. Our study suggests that recreational drug use is popular among Chinese MSM and is associated with significantly increased HIV infection risk. HIV prevention intervention programs should reduce both drug use and risky sexual behaviors in this population.

  13. Development and evaluation of a solid oral dosage form for an artesunate and mefloquine drug combination / Abel Hermanus van der Watt

    OpenAIRE

    Van der Watt, Abel Hermanus

    2014-01-01

    Malaria affects about forty percent of the world’s population. Annually more than 1.5 million fatalities due to malaria occur and parasite resistance to existing antimalarial drugs such as mefloquine has already reached disturbingly high levels in South-East Asia and on the African continent. Consequently, there is a dire need for new drugs or formulations in the prophylaxis and treatment of malaria. Artesunate, an artemisinin derivative, represents a new category of antimalarials that is eff...

  14. Willingness-to-pay for a rapid malaria diagnostic test and artemisinin-based combination therapy from private drug shops in Mukono district, Uganda

    OpenAIRE

    Hansen, Kristian Schultz; Pedrazzoli, Debora; Mbonye, Anthony; Clarke, Sian; Cundill, Bonnie; Magnussen, Pascal; Yeung, Shunmay

    2012-01-01

    In Uganda, as in many parts of Africa, the majority of the population seek treatment for malaria in drug shops as their first point of care; however, parasitological diagnosis is not usually offered in these outlets. Rapid diagnostic tests (RDTs) for malaria have attracted interest in recent years as a tool to improve malaria diagnosis, since they have proved accurate and easy to perform with minimal training. Although RDTs could feasibly be performed by drug shop vendors, it is not known how...

  15. The Synergistic (MARATHON) Effect of Combined Methamphetamine with Sexual Stimulant Drugs on Increasing the Likelihood of High-Risk Sexual Behaviors

    OpenAIRE

    Hosseinifard, Seyed Mehdi; Ahmadian, Alireza; Smaeelifar, Neda

    2014-01-01

    Background Chronic drug abuse and sexual dysfunction specifically erectile dysfunction may lead drug abusers to seek over-the-counter or non-prescription medications, out of which Sildenafil citrate, sold as the trade name of Viagra® can be considered as a prime and important treatment. Therefore, the research purpose was to draw a comparison and review the role of methamphetamine abuse and sildenafil use in increasing the likelihood of high-risk sexual behaviors (both concomitant and non-con...

  16. Production of polymeric micelles by microfluidic technology for combined drug delivery: application to osteogenic differentiation of human periodontal ligament mesenchymal stem cells (hPDLSCs)

    OpenAIRE

    Capretto, L.; Mazzitelli, S.; Colombo, G.; Piva, R.; Penolazzi, L.; Vecchiatini, R.; Zhang, X.; Nastruzzi, C.

    2013-01-01

    The current paper reports the production of polymeric micelles (PMs), based on pluronic block-copolymers, as drug carriers, precisely controlling the cellular delivery of drugs with various physico-chemical characteristics. PMs were produced with a microfluidic platform to exploit further control on the size characteristic of the PMs. PMs were designed for the co-delivery of dexamethasone (Dex) and ascorbyl-palmitate (AP) to in vitro cultured human periodontal ligament mesenchymal stem ce...

  17. A novel enzymatically-mediated drug delivery carrier for bone tissue engineering applications: combining biodegradable starch-based microparticles and differentiation agents

    OpenAIRE

    Balmayor, Elizabeth Rosado; Tuzlakoglu, K.; Marques, A.P.; Azevedo, Helena S.; Reis, R.L.

    2008-01-01

    In many biomedical applications, the performance of biomaterials depends largely on their degradation behavior. For instance, in drug delivery applications, the polymeric carrier should degrade under physiological conditions slowly releasing the encapsulated drug. The aim of this work was, therefore, to develop an enzymaticmediated degradation carrier system for the delivery of differentiation agents to be used in bone tissue engineering applications. For that, a polym...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts ... and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children Drug Abuse Hurts ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were ...

  20. Simultaneous detection of antibiotics and other drug residues in the dissolved and particulate phases of water by an off-line SPE combined with on-line SPE-LC-MS/MS: Method development and application.

    Science.gov (United States)

    Tlili, Ines; Caria, Giovanni; Ouddane, Baghdad; Ghorbel-Abid, Ibtissem; Ternane, Riadh; Trabelsi-Ayadi, Malika; Net, Sopheak

    2016-09-01

    Due to their widespread use in human and animal healthcare, antibiotics and other drug residues are ubiquitous in the aquatic environment. Given their potential impacts on ecosystem functioning and public health, the quantification of environmental drug residues has become a necessity. Various analysis techniques have been found to be suitable for reliable detection of such compounds. However, quantification can be difficult because these compounds are present at trace or ultra-trace levels. Consequently, the accuracy of environmental analyses depends on both the efficiency and the robustness of the extraction and quantification method. In this work, an off-line solid-phase extraction (SPE) combined with on-line SPE-LC-MS/MS was applied to the simultaneous extraction and quantification of 26 pharmaceutical products, including 18 antibiotics, dissolved in a water phase. Optimal conditions were determined and then applied to assess the contamination level of the targeted drug residues in water collected from four sites in Northern France: a river, the input and output of an aerated lagoon, and a wastewater treatment plant. Drug residues associated with suspended solid matter (SSM) were also quantified in this work using pressurized liquid extraction (PLE) combined with an on-line SPE-LC-MS/MS system in order to complete an assessment of the degree of total background pollution. PMID:27151499

  1. [Drug-drug interactions in antirheumatic treatment].

    Science.gov (United States)

    Krüger, K

    2012-04-01

    Clinically relevant drug-drug interactions contribute considerably to potentially dangerous drug side-effects and are frequently the reason for hospitalization. Nevertheless they are often overlooked in daily practice. For most antirheumatic drugs a vast number of interactions have been described but only a minority with clinical relevance. Several potentially important drug interactions exist for non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, azathioprine, mycophenolate-mofetil and especially for cyclosporin A. Most importantly co-medication with methotrexate and sulfmethoxazole trimethoprim as well as azathioprine and allopurinol carries the risk of severe, sometimes life-threatening consequences. Nevertheless, besides these well-known high-risk combinations in each case of polypharmacy with antirheumatic drugs it is necessary to bear in mind the possibility of drug interactions. As polypharmacy is a common therapeutic practice in older patients with rheumatic diseases, they are at special risk. PMID:22527215

  2. Quality of Artemisinin-Based Combination Formulations for Malaria Treatment: Prevalence and Risk Factors for Poor Quality Medicines in Public Facilities and Private Sector Drug Outlets in Enugu, Nigeria

    OpenAIRE

    Harparkash Kaur; Elizabeth Louise Allan; Ibrahim Mamadu; Zoe Hall; Ogochukwu Ibe; Mohamed El Sherbiny; Albert van Wyk; Shunmay Yeung; Isabel Swamidoss; Green, Michael D.; Prabha Dwivedi; Maria Julia Culzoni; Siân Clarke; David Schellenberg; Fernández, Facundo M.

    2015-01-01

    Background Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artem...

  3. CONCEPT OF DRUG INTERACTION

    Directory of Open Access Journals (Sweden)

    Singh Nidhi

    2012-07-01

    Full Text Available Drug interaction is an increasingly important cause of adverse reactions (ADR, and is the modification of the effect of one drug (object by the prior or concomitant administration of another drug (precipitant drug. Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  4. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments

    Energy Technology Data Exchange (ETDEWEB)

    Boleda, Ma Rosa [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain); Galceran, Ma Teresa [University of Barcelona, Department Analytical Chemistry, Av. Diagonal 647, 08028 Barcelona (Spain); Ventura, Francesc, E-mail: fventura@agbar.es [AGBAR-Aiguees de Barcelona, Gral Batet 5-7, 08028 Barcelona (Spain)

    2011-06-15

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies {>=}94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. - Highlights: > The presence of pharmaceuticals and drugs of abuse in surface water was demonstrated. > Elimination in both potabilization processes reached levels >99% for most compounds. > Four pharmaceuticals and three drugs of abuse survived the potabilization process. - The efficiency of potabilization processes to eliminate or transform pharmaceuticals and illicit drugs is evaluated.

  5. Stability behaviour of antiretroviral drugs and their combinations. 2: Characterization of interaction products of lamivudine and tenofovir disoproxil fumarate by mass and NMR spectrometry.

    Science.gov (United States)

    Kurmi, Moolchand; Kushwah, Bhoopendra Singh; Sahu, Archana; Narayanam, Mallikarjun; Singh, Saranjit

    2016-06-01

    This study focused on drug-drug interaction behaviour among lamivudine (3TC) and tenofovir disoproxil fumarate (TDF), the two anti-retroviral drugs. Apart from pre-known degradation products of individual drugs, a total of twelve interaction products were detected by high performance liquid chromatography (HPLC) using a C18 column as the stationary phase, and methanol and ammonium formate in gradient mode as the mobile phase. The same HPLC method was employed for liquid chromatography-high resolution mass spectrometry (LC-HRMS) and liquid chromatography-multi stage mass spectrometry (LC-MS(n)). For the characterization of interaction products, stability samples were subjected to LC-HRMS, LC-MS(n) and online hydrogen/deuterium exchange studies. Two isomeric interaction products were isolated and subjected to 1D and 2D nuclear magnetic resonance (NMR) studies. The collated information was utilized for the characterization of all twelve interaction products of the two drugs. Pathway of their formation was also outlined. PMID:27042808

  6. Behavior of pharmaceuticals and drugs of abuse in a drinking water treatment plant (DWTP) using combined conventional and ultrafiltration and reverse osmosis (UF/RO) treatments

    International Nuclear Information System (INIS)

    The behavior along the potabilization process of 29 pharmaceuticals and 12 drugs of abuse identified from a total of 81 compounds at the intake of a drinking water treatment plant (DWTP) has been studied. The DWTP has a common treatment consisting of dioxychlorination, coagulation/flocculation and sand filtration and then water is splitted in two parallel treatment lines: conventional (ozonation and carbon filtration) and advanced (ultrafiltration and reverse osmosis) to be further blended, chlorinated and distributed. Full removals were reached for most of the compounds. Iopromide (up to 17.2 ng/L), nicotine (13.7 ng/L), benzoylecgonine (1.9 ng/L), cotinine (3.6 ng/L), acetaminophen (15.6 ng/L), erythromycin (2.0 ng/L) and caffeine (6.0 ng/L) with elimination efficiencies ≥94%, were the sole compounds found in the treated water. The advanced treatment process showed a slightly better efficiency than the conventional treatment to eliminate pharmaceuticals and drugs of abuse. - Highlights: → The presence of pharmaceuticals and drugs of abuse in surface water was demonstrated. → Elimination in both potabilization processes reached levels >99% for most compounds. → Four pharmaceuticals and three drugs of abuse survived the potabilization process. - The efficiency of potabilization processes to eliminate or transform pharmaceuticals and illicit drugs is evaluated.

  7. Comparisons of the Pharmacokinetic Profile of Four Bioactive Components after Oral Administration of Gan-Sui-Ban-Xia Decoction Plus-Minus Gansui and Gancao Drug Combination in Normal Rats

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2015-05-01

    Full Text Available Gan-Sui-Ban-Xia Decoction (GSBXD was first presented by Zhang Zhongjing in the book Synopsis of Golden Chamber during the Han Dynasty period. The formula was then used for the treatment of persistent fluid retention with floating pulse in Traditional Chinese Medicine (TCM, which in modern medicine is known as malignant ascites. Here, a rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS method has been developed for the determination of glycyrrhizinic acid, liquiritin, paeoniflorin, albiflorin after oral administration of GSBXD plus-minus Gansui and Gancao anti-drug combination to investigate the possible pharmacokinetic profile differences of different prescriptions with GSBXD in normal rats. The differences of pharmacokinetic parameters among groups were tested by the Student’s t-test with p < 0.05 as the level of significance. Significant differences were found between the Gansui and Gancao anti-drug combination and other herbs in GSBXD on pharmacokinetic profile of glycyrrhizinic acid, liquiritin, paeoniflorin and albiflorin. The obtained knowledge might contribute to the rationality of the clinic use of GSBXD and also reveal the compatibility conditions of the Gansui and Gancao anti-drug combination.

  8. External Application of Chinese Drugs on Acupoint Shenque Combined with Salpingostomy for Treatment of Sterility Caused by Obstruction of the Fallopian Tube-A Clinical Report of 45 Cases

    Institute of Scientific and Technical Information of China (English)

    Huang Jianmei; Wang Wei

    2005-01-01

    Objective: To observe the therapeutic effect of external application of Chinese drugs on acupoint Shenque (CV 8) combined with salpingostomy for treatment of sterility caused by obstruction of the fallopian tube.Method: 75 cases were randomly divided into the following 2 groups. Forty-five patients in the treatment group were treated with external application of Chinese drugs on acupoint Shenque (CV 8) combined with salpingostomy, while 30 patients in the control group were treated with salpingostomy only. Results: The results showed that in the treatment group, 26 cases were cured, 11 cases improved, and 8 cases failed, with a total effective rate of 82.22%; while in the control group, 14 cases were cured, 7 cases improved, and 9 cases failed, with a total effective rate of 70.00%. There is a significant difference in the total effective rate between the two groups (P<0.05). Conclusion: The therapeutic effect of external application of Chinese drugs on acupoint Shenque combined with salpingostomy is better than that of salpingostomy only.

  9. Herbal drugs and drug interactions

    Directory of Open Access Journals (Sweden)

    Gül Dülger

    2012-01-01

    Full Text Available Herbal drugs are defined as any form of a plant or plant product that contains a single herb or combinations of herbs that are believed to have complementary effects. Although they are considered to be safe, because they are natural, they may have various adverse effects, and may interact with other herbal products or conventional drugs. These interactions are especially important for drugs with narrow therapeutic indices.In the present study, pharmacokinetic and pharmacodynamic interactions of some most commanly used herbals (St John's wort, ginkgo biloba, ginseng, ginger, garlic, echinacea, ephedra and valerian with the conventional drugs were reviewed. Pharmacokinetic interactions involve mainly induction or inhibition of the cytochrome P450 isozymes and p-glycoproteins by the herbal medicine, thus changing the absorption and/or elimination rate and consequently the efficacy of the concommitantly used drugs. St John's wort, a well known enzyme inducer, decreases the efficacy of most of the other drugs that are known to be the substrates of these enzymes.Pharmacodynamic interactions may be due to additive or synergistic effects which results in enhanced effect or toxicity, or herbal medicines with antagonistic properties reduce drug efficacy and result in therapeutic failure. For exampla, St John's wort may have synergistic effects with other antidepressant drugs used by the patient, resulting in increased CNS effects.Herbals like ginseng, ginkgo, garlic, ginger were reported to increase bleeding time, thus potentiating the effect of anticoagulant and antithrombotic agents. In conclusion, patients should be warned against the interaction between the herbal products and conventional medicines.

  10. How sulfadoxine-pyrimethamine (SP was perceived in some rural communities after phasing out chloroquine (CQ as a first-line drug for uncomplicated malaria in Tanzania: lessons to learn towards moving from monotherapy to fixed combination therapy

    Directory of Open Access Journals (Sweden)

    Nsimba Stephen ED

    2006-01-01

    health workers considered the drug to be good and effective against malaria. Such negative perception towards SP highlights the need to start earlier sensitization and educational campaigns to the rural communities for a new drug program to ensure its success. Messages should clearly state what should be expected from the new drug (Coartem, before its introduction. This is important especially as Tanzania is expected to move towards the expensive but efficacious and effective fixed-combination (Coartem anti-malarial therapy early next year (2006.

  11. Stability behaviour of antiretroviral drugs and their combinations. 3: Characterization of interaction products of emtricitabine and tenofovir disoproxil fumarate by mass spectrometry.

    Science.gov (United States)

    Kurmi, Moolchand; Singh, Dilip Kumar; Tiwari, Shristy; Sharma, Parul; Singh, Saranjit

    2016-09-01

    The present study investigated drug-drug interaction behaviour of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) under solid state stability test conditions. Six interaction products were separated and detected by high performance liquid chromatography coupled to photodiode array detector (HPLC-PDA) using C18 column. The same were characterized using LC-high resolution mass spectrometry (LC-HRMS), LC-multi stage mass spectrometry (LC-MS(n)) and online hydrogen/deuterium (H/D) exchange studies. The interaction pathway among the two drugs was outlined based on the elucidated structures. Four of the six interaction products were also formed in marketed tablets containing FTC and TDF (along with efavirenz (EFV)) that were kept without packing under accelerated condition of 40°C/75% RH till 6 months. PMID:27344633

  12. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

    Directory of Open Access Journals (Sweden)

    Dillip Angel

    2010-06-01

    Full Text Available Abstract Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS and in Ifakara town. Data collection consisted of: 1 yearly censuses of shops selling drugs; 2 collection of monthly data on availability of anti-malarials in public health facilities; and 3 retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Results Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008 and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008 of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock, but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock, but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti

  13. Cardiovascular safety of combination therapies with incretin-based drugs and metformin compared with a combination of metformin and sulphonylurea in type 2 diabetes mellitus – a retrospective nationwide study

    DEFF Research Database (Denmark)

    Mogensen, U M; Andersson, Charlotte; Fosbøl, E L;

    2014-01-01

    AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) agonists are widely used in combinations with metformin in the treatment of type 2 diabetes; however, data on long-term safety compared with conventional combination therapies are limited. METHODS: Danish individuals...... with metformin were safe compared with conventional combinations of glucose-lowering therapy. Use of incretin-based therapy may be target for strategies to lower CV risk in type 2 diabetes, although it should be recognized that the multivariable analysis may not have fully accounted for important...

  14. Computer modeling of airway deposition distribution of Foster(®) NEXThaler(®) and Seretide(®) Diskus(®) dry powder combination drugs.

    Science.gov (United States)

    Jókay, Ágnes; Farkas, Árpád; Füri, Péter; Horváth, Alpár; Tomisa, Gábor; Balásházy, Imre

    2016-06-10

    Asthma is a serious global health problem with rising prevalence and treatment costs. Due to the growing number of different types of inhalation devices and aerosol drugs, physicians often face difficulties in choosing the right medication for their patients. The main objectives of this study are (i) to elucidate the possibility and the advantages of the application of numerical modeling techniques in aerosol drug and device selection, and (ii) to demonstrate the possibility of the optimization of inhalation modes in asthma therapy with a numerical lung model by simulating patient-specific drug deposition distributions. In this study we measured inhalation parameter values of 25 healthy adult volunteers when using Foster(®) NEXThaler(®) and Seretide(®) Diskus(®). Relationships between emitted doses and patient-specific inhalation flow rates were established. Furthermore, individualized emitted particle size distributions were determined applying size distributions at measured flow rates. Based on the measured breathing parameter values, we calculated patient-specific drug deposition distributions for the active components (steroid and bronchodilator) of both drugs by the help of a validated aerosol lung deposition model adapted to therapeutic aerosols. Deposited dose fractions and deposition densities have been computed in the entire respiratory tract, in distinct anatomical regions of the airways and at the level of airway generations. We found that Foster(®) NEXThaler(®) deposits more efficiently in the lungs (average deposited steroid dose: 42.32±5.76% of the nominal emitted dose) than Seretide(®) Diskus(®) (average deposited steroid dose: 24.33±2.83% of the nominal emitted dose), but the variance of the deposition values of different individuals in the lung is significant. In addition, there are differences in the required minimal flow rates, therefore at certain patients Seretide(®) Diskus(®) or pMDIs could be a better choice. Our results show that

  15. Drug Facts

    Medline Plus

    Full Text Available ... Abuse Hurts Unborn Children Drug Abuse Hurts Your Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Addiction? Addiction Risk Factors Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn ...

  17. Formulation development and evaluation of fast disintegrating tablets of salbutamol sulphate, cetirizine hydrochloride in combined pharmaceutical dosage form: a new era in novel drug delivery for pediatrics and geriatrics.

    Science.gov (United States)

    Sharma, Deepak; Singh, Gurmeet; Kumar, Dinesh; Singh, Mankaran

    2015-01-01

    The objective of the present study was to prepare the fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form for respiratory disorders such as bronchitis, asthma, and coughing for pediatrics and geriatrics. The tablets were prepared by direct compression technique. Superdisintegrant such as Sodium Starch Glycolate was optimized as 4% on the basis of least disintegration time. Different binders such as MCC and PVP K-30 were optimized along with optimized superdisintegrant concentration. 1% MCC was selected as optimum binder concentration on the basis of least disintegration time. The tablets were evaluated for hardness, friability, weight variation, wetting time, disintegration time, and drug content uniformity. Optimized formulation was further evaluated by in vitro dissolution test, drug-excipient compatibility, and accelerated stability study. Percent weight variation and content uniformity were within the acceptable limit. The friability was less than 1%. The wetting time and disintegration time were practically good for all formulations. FTIR studies and accelerated stability study showed that there was no interaction between the drug and excipients. It was concluded that, by employing commonly available pharmaceutical excipients such as superdisintegrants, hydrophilic and swellable excipients and proper filler, a fast disintegrating tablet of Salbutamol Sulphate, Cetirizine Hydrochloride in combined tablet dosage form, were formulated successfully with desired characteristics. PMID:25810924

  18. Drug: D02065 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available am sodium mixt J01R COMBINATIONS OF ANTIBACTERIALS J01RA Combinations of antibacterials J01RA01 Penicillins,... combinations with other antibacterials D02065 Ampicillin sodium - sulbactam sodium mixt USP drug classifica

  19. On the Ideal Quality Control Specification of Compound Prescription -- Taking thought for the New Ingredients Produced in the Single Drugs Combining Process in Compound Prescription

    Institute of Scientific and Technical Information of China (English)

    刘建利

    2002-01-01

    @@ Effectiveness, safety and quality controllability are the three basic and most important premises for evaluating the quality of drugs. Having undergone clinical tests and been verified in thousands of years, the effectiveness and safety of compound prescription, the chief form of medication in TCM, have been proved reliable. Sometimes due to the lack of quality controllability, incorrect drug or method of preparing being used, so poor therapeutic effect can be seen, though diagnosis and prescription are correct. Quality uncontrollability is also one of the important reasons that causes difficulty for TCM preparation to enter international market. In order to ensure the effectiveness and safety of TCM compound prescription and the entering of TCM preparation into international market, strict quality control specifications should be defined. Although wide attention has been paid to this task, how to define the specifications is still under discussion.

  20. In vitro killing of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin in combination with its active metabolite ciprofloxacin using clinically relevant drug concentrations in the dog and cat.

    Science.gov (United States)

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J

    2012-03-23

    Enrofloxacin is a fluoroquinolone antibacterial agent used to treat infections in companion animals. Enrofloxacin's antimicrobial spectrum includes Gram positive and Gram-negative bacteria and demonstrates concentration-dependent bacteriocidal activity. In dogs and cats, enrofloxacin is partially metabolized to ciprofloxacin and both active agents circulate simultaneously in treated animals at ratios of approximately 60-70% enrofloxacin to 30-40% ciprofloxacin. We were interested in determining the killing of companion animal isolates of Escherichia coli, Staphylococcus pseudintermedius and Pseudomonas aeruginosa by enrofloxacin and ciprofloxacin combined using clinically relevant drug concentrations and ratios. For E. coli isolates exposed to 2.1 and 4.1μg/ml of enrofloxacin/ciprofloxacin at 50:50, 60:40 and 70:30 ratios, a 1.7-2.5log(10) reduction (94-99% kill) was seen following 20min of drug exposure; 0.89-1.7log(10) (92-99% kill) of S. pseudintermedius following 180min of drug exposure; 0.85-3.4log(10) (98-99% kill) of P. aeruginosa following 15min of drug exposure. Killing of S. pseudintermedius was enhanced in the presence of enrofloxacin whereas killing of P. aeruginosa was enhanced in the presence of ciprofloxacin. Antagonism was not seen when enrofloxacin and ciprofloxacin were used in kill assays. The unique feature of partial metabolism of enrofloxacin to ciprofloxacin expands the spectrum of enhanced killing of common companion animal pathogens. PMID:21925810

  1. Combined Neuropeptide S and D-Cycloserine Augmentation Prevents the Return of Fear in Extinction-Impaired Rodents: Advantage of Dual versus Single Drug Approaches

    OpenAIRE

    Sartori, Simone B.; Maurer, Verena; Murphy, Conor; Schmuckermair, Claudia; Muigg, Patrick; Neumann, Inga D.; Whittle, Nigel; Singewald, Nicolas

    2015-01-01

    Background: Despite its success in treating specific anxiety disorders, the effect of exposure therapy is limited by problems with tolerability, treatment resistance, and fear relapse after initial response. The identification of novel drug targets facilitating fear extinction in clinically relevant animal models may guide improved treatment strategies for these disorders in terms of efficacy, acceleration of fear extinction, and return of fear. Methods: The extinction-facilitating potential ...

  2. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

    OpenAIRE

    Dillip Angel; Goodman Catherine; Hetzel Manuel W; Alba Sandra; Liana Jafari; Mshinda Hassan; Lengeler Christian

    2010-01-01

    Abstract Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study ...

  3. Development of EGFR-Targeted Polymer Blend Nanocarriers for Combination Paclitaxel/Lonidamine Delivery to Treat Multi-Drug Resistance in Human Breast and Ovarian Tumor Cells

    OpenAIRE

    Milane, Lara; Duan, Zhenfeng; Amiji, Mansoor

    2010-01-01

    Multi-drug resistant (MDR) cancer is a significant clinical obstacle and is often implicated in cases of recurrent, non-responsive disease. Targeted nanoparticles were made by synthesizing a poly(D,L-lactide-co-glycolide)/poly(ethylene glycol)/epidermal growth factor receptor targeting peptide (PLGA/PEG/EGFR-peptide) construct for incorporation in poly(epsilon-caprolactone) (PCL) nanoparticles. MDR was induced in a panel of nine human breast and ovarian cancer cell lines using hypoxia. EGFR-t...

  4. Simultaneous determination of timolol maleate in combination with some other anti-glaucoma drugs in rabbit aqueous humor by high performance liquid chromatography-tandem mass spectroscopy.

    Science.gov (United States)

    Hassib, Sonia T; Elkady, Ehab F; Sayed, Rawda M

    2016-06-01

    In this work, a sensitive, selective, accurate and precise LC-MS/MS method has been developed for the simultaneous determination of an anti-glaucoma ß-blocker, timolol maleate (TIM) with other co-administered anti-glaucoma drugs of different classes, namely; dorzolamide hydrochloride (DOR), brinzolamide (BRZ) and brimonidine tartrate (BRM) in rabbit aqueous humor (AH) using eslicarbazepine as an internal standard (IS). Liquid-liquid extraction was used for the purification and pre-concentration of analytes from rabbit AH matrix. The chromatographic separation was achieved using a mobile phase consisting of 10mM ammonium formate pH=7: methanol: acetonitrile (5: 50: 45, v/v/v) in isocratic mode of elution at a flow rate of 0.8mL/min on an INERTSIL(®) C18 ODS-3 column (150mm×4.6mm, 3.5μm). The method was operated using electrospray ionization source in the positive ionization mode prior to detection by multiple reaction monitoring (MRM) at the following transitions: m/z 317.2→261.0 for TIM, m/z 325.1→199.0 for DOR, m/z 384.2→281.0 for BRZ, m/z 292.1→212.0 for BRM and m/z 255.0→237.0 for IS. The separation was done in only 3min and the lower limit of quantitation (LLOQ) was (50ng/ml) for all cited drugs. A detailed validation of the bio-analytical method was performed as mentioned in US-FDA and EMA guidelines and the standard calibration curves were found to be linear in the range (50-5000ng/ml) for all drugs with good mean regression coefficient for all drugs. PMID:27085020

  5. UV-vis spectra of the anticancer camptothecin family drugs in aqueous solution: specific spectroscopic signatures unraveled by a combined computational and experimental study.

    Science.gov (United States)

    Sanna, Nico; Chillemi, Giovanni; Gontrani, Lorenzo; Grandi, Andrea; Mancini, Giordano; Castelli, Silvia; Zagotto, Giuseppe; Zazza, Costantino; Barone, Vincenzo; Desideri, Alessandro

    2009-04-23

    The ultraviolet-visible absorption spectrum of camptothecin (CPT) has been been recorded in aqueous solution at pH 5.3, where the equilibrium among the different CPT forms is shifted toward the lactonic one. Time-dependent density functional theory (TD-DFT) computations lead to a remarkable reproduction of the experimental spectrum only upon addition of explicit water molecules in interaction with specific moieties of the camptothecin molecule. Molecular dynamics (MD) simulations enforcing boundary periodic conditions for CPT embedded with 865 water molecules, with a force field derived from DFT computations, show that the experimental spectrum is due to the contributions of CPT molecules with different solvation patterns. A similar solvent effect is observed for several CPT derivatives, including the clinically relevant SN-38 and topotecan drugs. The quantitative agreement between TD-DFT/MD computations and experimental data allow us to identify specific spectroscopic signatures diagnostic of the drug environment and to develop procedures that can be used to monitor the drug-DNA/protein interaction. PMID:19334673

  6. Clinical and laboratory assessment of a combination of drugs with radiation. Coordinated programme on improvement in radiotherapy of cancer using modifiers of radiosensitivity of cells

    International Nuclear Information System (INIS)

    Applications were clinically studied of misonidazole (MISO) as a hypoxic cell radiosensitizer with pharmacokinetic studies. Work with desmethylmisonidazole was focused on its penetration into the CNS because its low lipophilicity would predict poorer access than MISO. Laboratory work was focused on the interaction of hyperthermia with drugs. Cytotoxicity of MISO induced by hyperthermia was studied. Heat response following hypoxic pretreatment with MISO of EMT6 spheroids showed marked enhancement of subsequent heat killing dependent on the duration of the hypoxic pretreatment. The effect was studied in vitro of preheat temperature at modest temperatures (39 to 430C) on thermal tolerance and subsequent hyperthermic (43 to 440C) interaction with bleomycin, adriamycin and BCNU. Interaction between several cytotoxic drugs and two potentially critical normal tissues, skin and bone marrow was studied in the mouse. No increase in the heat reaction in the skin of the mouse foot was observed following single injections of adriamycin, bleomycin or 5 daily doses of bleomycin together with a single heat treatment. Single doses of BCNU and CTX increased the heat reaction. The radioprotector WR2721 failed to protect against either the heat or heat drug reactions from CTX and BCNU

  7. Combination of survivin siRNA with neoadjuvant chemotherapy enhances apoptosis and reverses drug resistance in breast cancer MCF-7 cells

    Directory of Open Access Journals (Sweden)

    Honglin Dong

    2015-01-01

    Conclusion: Survivin siRNA combined with the neoadjuvant chemotherapy can significantly enhance the sensitivity of MCF-7 cells to chemotherapeutics and cell apoptosis. This technology has important potential value in the therapeutic study of breast cancer.

  8. Evaluation of the analgesic and anti-inflammatory activity of fixed dose combination: Non-steroidal anti-inflammatory drugs in experimental animals

    Directory of Open Access Journals (Sweden)

    Amit Lahoti

    2014-01-01

    Conclusion: Combining paracetamol with ibuprofen enhances analgesic/anti-inflammatory activity over their individual component but potentiation of analgesic activity of diclofenac was not seen when paracetamol was added to it.

  9. Drugs Approved for Lung Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Lung Cancer This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic and brand names. This page also lists common drug combinations used in lung ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between Drug Abuse and HIV/AIDS Recovery & Treatment Drug Treatment Facts Does Drug Treatment Work? Types of Drug Treatment What Is a Relapse? ...

  11. Preclinical Evaluation on the Tumor Suppression Efficiency and Combination Drug Effects of Fermented Wheat Germ Extract in Human Ovarian Carcinoma Cells

    OpenAIRE

    Chia-Woei Wang; Chien-Kai Wang; Yu-Jia Chang; Chen-Yen Choong; Chi-Shian Lin; Cheng-Jeng Tai; Chen-Jei Tai

    2015-01-01

    Fermented wheat germ extract (FWGE) is a nutrient supplement and a potential antitumor ingredient for developing an integrated chemotherapy with standard chemotherapeutic drugs for treating ovarian cancer patients. In this study, we evaluated the tumor suppression efficiency of FWGE in human ovarian carcinoma cells, SKOV-3 and ES-2, and found the half-maximal inhibitory concentrations (IC50s) to be 643.76 μg/mL and 246.11 μg/mL after 48 h of FWGE treatment. FWGE treatment also induced program...

  12. 臭氧联合药物治疗阴道炎的临床观察%Clinical Observation of Medical Ozone Combined with Drugs in the Treatment of Vaginitis

    Institute of Scientific and Technical Information of China (English)

    王巍

    2014-01-01

    Objective:To investigate the effect of Medical ozone combination of drugs treatment of vagini-tis .Methods :Select Candida ,bacterial and trichomonas vaginitis patients with a total 240 cases ,according to treatment methods ,the three kinds of infl ammation of the patients were randomly divided into two groups . Treatment group treated with ozone therapy instrument combination of drugs ;the control group according to the different nature of inflammation to take medication .Results:Candida ,bacterial and trichomonas vagini-tis ,the effective of treatment group was 94 .1% ,while the control group was 81 .6% ,the efficacy of treat-ment group was signifi cantly higher then control group .Conclusion:The effect of Medical ozone combina-tion of drugs treatment of vaginitis is effective and safe treatment of vaginal infl ammation ,worthy of promo-tio n .%目的:观察臭氧联合药物治疗阴道炎的临床疗效。方法:将240例滴虫性阴道炎、外阴阴道假丝酵母菌病、细菌性阴道病患者随机分为2组,治疗组120例自愿应用医用臭氧治疗仪治疗,并局部用药;对照组120例常规用药,观察2组临床疗效。结果:治疗组与对照组的有效率分别为94.1%和81.6%,2组比较有显著性差异( P<0.05)。结论:臭氧联合局部用药治疗阴道炎效果好,值得临床推广。

  13. 近代联用技术在生物大分子药物研究中应用进展%Progress on Studies and Applications of Modern Combined Techniques in Biomacromolecule Drugs

    Institute of Scientific and Technical Information of China (English)

    王铭章; 陈执中

    2011-01-01

    Since the 1990s. following the development of new combined techniques and gene research, thebiomacromolecule drugs were concerned by chemical and medical workers. Now, this subject has become aresearch hotpot.In this paper, the progress on studies and applications of some modern combined techniques in biomacromolecule drugs are reviewed, including surface plasmon resonance-cyclic voltammetry (SPR-CV),biomolecular interaction analysis-mass spectrometry (BIA/MS), microfluidics chip capillary electrophoresis-mass spectrometry (Chip-CE-MS), two-dimensional liquid chromatography coupled to tandem mass spectrometry (2D-LC coupled MS/MS) and LC-MS-NMR.The applications of these new combined techniques will open up broad prospect for the research and development of biomacromolecule drugs.%20世纪90年代以来,随着联用技术和基因研究的发展,生物大分子药物的研究深受化学和医学工作者的关注,成为研究热点之一.本文综述了表面等离子共振-环伏安法(SPR-CV)、生物分子相互作用分析-质谱法(BIA/MS),微流路芯片毛细管电泳-质谱法(Chip-CE-MS)、离线二维液相色谱综合串联质谱法(2D-LC coupled MS/MS)及液相色谱-质谱-核磁共振(LC-MS-NMR)联用技术在生物大分子药物中的研究应用进展.这些联用技术的应用将为生物大分子药物的研究开发开拓广阔的前景.

  14. Lumbar disc protrusion therapy by combination drug administration in epidural space%硬膜外腔联合用药治疗腰椎间盘突出症

    Institute of Scientific and Technical Information of China (English)

    尹美华; 杨德荣; 许晶; 马玉清

    2003-01-01

    @@ BACKGROUND: Lumbar disc protrusion was a syndrome dueto degeneration of disc, disruption of fibrous tings and protrusion ofnucleus pulposus and stimulation of cauda equina. It was the mostcommon cause of leg and back pain. it had a high incidence rate andthe patients suffered too greatly to normal work and life. Afternon-operative therapy, symptoms of most patients disappeared orrelieved. Only 10% to 15% of the patients needed operation. Re-cently, combination drug administration in epidural space were usedin lumbar disc protrusion therapy with a highly successful rate andhttle danger.

  15. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... vomiting to life-threatening anaphylaxis . A true drug allergy is caused by a series of chemical steps ...

  16. Simultaneous determination of some antiprotozoal drugs in different combined dosage forms by mean centering of ratio spectra and multivariate calibration with model updating methods

    Directory of Open Access Journals (Sweden)

    Abdelaleem Eglal A

    2012-04-01

    Full Text Available Abstract Background Metronidazole (MET and Diloxanide Furoate (DF, act as antiprotozoal drugs, in their ternary mixtures with Mebeverine HCl (MEH, an effective antispasmodic drug. This work concerns with the development and validation of two simple, specific and cost effective methods mainly for simultaneous determination of the proposed ternary mixture. In addition, the developed multivariate calibration model has been updated to determine Metronidazole benzoate (METB in its binary mixture with DF in Dimetrol® suspension. Results Method (I is the mean centering of ratio spectra spectrophotometric method (MCR that depends on using the mean centered ratio spectra in two successive steps that eliminates the derivative steps and therefore the signal to noise ratio is enhanced. The developed MCR method has been successfully applied for determination of MET, DF and MEH in different laboratory prepared mixtures and in tablets. Method (II is the partial least square (PLS multivariate calibration method that has been optimized for determination of MET, DF and MEH in Dimetrol ® tablets and by updating the developed model, it has been successfully used for prediction of binary mixtures of DF and Metronidazole Benzoate ester (METB in Dimetrol ® suspension with good accuracy and precision without reconstruction of the calibration set. Conclusion The developed methods have been validated; accuracy, precision and specificity were found to be within the acceptable limits. Moreover results obtained by the suggested methods showed no significant difference when compared with those obtained by reported methods. Graphical Abstract

  17. Conceptualization and Analysis of A Novel Combined Drug pre-procurement Scheme for China Public Hospitals%公立医院药品零差率集中招标预购制初步构想及分析

    Institute of Scientific and Technical Information of China (English)

    夏怡; 柴静; 王德斌; 辛昌茂; 赵林海

    2013-01-01

    Objective:To conceive a novel combined drug pre-procurement scheme for public hospitals so as to tackle the long exiting drug abuses and over pricing in China.Methods:Utiliaing comprehensive methods including stakeholder analysis,systems thinking and scenario comparisons.Results:The study worked out:(1) A new conceptual scheme combing collective biding for drug provision companies,zero-profit selling of drugs by caregivers and prepayment contracts between companies and caregivers; (2) Key factors affecting the scheme implemention; (3) Main alternative strategies tacking potential problems in implementing the scheme.Conclusion:The existing schemes of collective biding and zero-profit selling of drugs and the new proposed prepayment scheme act at different processes of drugs provision through utilization; put together,they will have cooperative effect in a synergetic way and radically reduce drug overselling by companies and over-prescribing by caregivers.%目的:探索新的公立医院药品采购机制,解决长期困扰我国医疗服务的药品滥用和价格虚高问题.方法:综合运用利益相关者分析、系统思维和假设情境比选等方法.结果:提出了在现有集中招标采购和零差价销售的基础上引入“总量预购”的制度构想,遘选出适用药品范圈、预购总量界定、中标厂商数量等关键因素,并针对这些因素提出了基本的设计策略.结论:现有药品集中招标采购和零差率销售与总量预购的作用各有侧重,联合运用有望收获协同功效,从而有效防范长期盛行的与药品相关的道德风险并成倍放大既有改革成果.

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs Charts Emerging Trends Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids ... because of treatment with HAART (highly active antiretroviral therapy), a combination of three or more antiretroviral medications ...

  19. Combination of electromembrane extraction and liquid-phase microextraction in a single step: Simultaneous group separation of acidic and basic drugs

    DEFF Research Database (Denmark)

    Huang, Chuixiu; Seip, Knut Fredrik; Gjelstad, Astrid;

    2015-01-01

    at high concentration. This approach was further investigated from human plasma. Extraction recoveries were strongly dependent on dilution of plasma with buffer and on extraction time. Finally, this simultaneous EME/LPME approach was evaluated in combination with liquid chromatography (LC...

  20. Comparative effect of amiodarone and amiodarone combined with other drugs in treatment of atrial fibrillation%胺碘酮与胺碘酮联合用药治疗心房纤颤疗效的比较

    Institute of Scientific and Technical Information of China (English)

    陈士良; 辛卫鹏; 高谊

    2011-01-01

    AIM: To compare the effect of amiodarone alone and amiodarone combined with other drugs in treatment of atrial fibrillation ( AF). METHODS: A total of 119 patients with AF were divided into single drug group ( n = 54) and multiple drug group ( n = 65 ). The single drug group received amiodarone treatment, whereas the multiple drug group received treatment of amiodarone together with glucose-insulin-potassium and diuretics. The recovery rate of AF and the maintenance rate of sinus rhythm were observed and compared after 6 months treatment. RESULTS: A significant increase in the recovery rate (from 80% vs. 94% ) and a significant decrease in the recovery duration of sinus rhythm from (55 ± 19) h to (39 ±15) h were observed in the multiple drug group. The maintenance rate increased from 81% to 95% , left atrial diameter decreased from (46 ±6) mm to (42 ±6) mm and the left ventricular diastolic diameter decreased from (52 ±7) mm to (45 ±6) mm in the multiple drug group. However, these phenomena were not seen in the single drug group. CONCLUSION: Compared with amiodarone alone, amiodarone combined with other drugs significantly increases the recovery rate and the maintenance rate in patients with AF.%目的:观察单纯用药与联合用药对心房纤颤(房颤)治疗效果.方法:选择119例房颤患者随机分为2组:单纯用药组54例,给予静脉胺碘酮150~300 mg后,继之以口服胺碘酮维持;联合用药组65例,使用极化液、硝酸甘油和小剂量利尿剂、胺碘酮,胺碘酮使用的剂量与方法同单纯用药组.观察两组房颤转复率和窦性维持率.结果:联合用药组的房颤转复率较单纯组明显提高(80% vs.94%,P<0.05),复律时间减少[(55±19)vs.(39±15)s,P<0.05],追踪复律半年后的维持率,联合用药组明显高于单纯用药组(81% vs.95%,P<0.05).复查B超显示:联合用药后,左心房内经明显缩小,从[(46±6)mm减少到(42±6)mm,P<0.05],左心

  1. Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal

    Directory of Open Access Journals (Sweden)

    Sow Diarietou

    2009-06-01

    Full Text Available Abstract Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years (ORa = 3.07 [1.49–6.29]; p = 0.004; and the profession of the head of household (retailer/employee versus farmer (ORa = 2.71 [1.34–5.48]; p = 0.006. Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013, and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001 were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

  2. Lead generation of heat shock protein 90 inhibitors by a combination of fragment-based approach, virtual screening, and structure-based drug design.

    Science.gov (United States)

    Miura, Takaaki; Fukami, Takaaki A; Hasegawa, Kiyoshi; Ono, Naomi; Suda, Atsushi; Shindo, Hidetoshi; Yoon, Dong-Oh; Kim, Sung-Jin; Na, Young-Jun; Aoki, Yuko; Shimma, Nobuo; Tsukuda, Takuo; Shiratori, Yasuhiko

    2011-10-01

    Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation and stabilization of its substrate proteins, known as client proteins. Many client proteins of Hsp90 are involved in tumor progression and survival and therefore Hsp90 can be a good target for developing anticancer drugs. With the aim of efficiently identifying a new class of orally available inhibitors of the ATP binding site of this protein, we conducted fragment screening and virtual screening in parallel against Hsp90. This approach quickly identified 2-aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex structures of the identified hits allowed us to promptly design CH5015765, which showed high affinity for Hsp90 and antitumor activity in human cancer xenograft mouse models. PMID:21875802

  3. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro (Kyoto Univ. (Japan). Faculty of Medicine)

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  4. Drug Facts

    Science.gov (United States)

    ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  5. Generic Drugs

    Science.gov (United States)

    ... name drug. A brand- name drug has a patent. When the patent runs out— usually after 10 to 14 years— ... if you do not have drug coverage. Condition Diabetes Heart failure High cholesterol Migraine Brand-name drug ...

  6. Synergistic iontophoretic drug delivery of risedronate sodium in combination with electroporation and chemical penetration enhancer: In-vitro and in-vivo evaluation

    OpenAIRE

    Swaroop R Lahoti; Shardul Dalal

    2015-01-01

    In the present investigation iontophoretic permeation of risedronate sodium (RS) through optimized gel based formulation was evaluated with respect to various electrical parameters like Current density and type of current. The study also involved enhancement the iontophoretic permeation of RS in combination with electroporation and chemical penetration enhancers with its in-vivo Pharmacokinetic evaluation. The permeation studies were carried through the human cadaver skin by using modified Fr...

  7. Piloting the Global Subsidy: The Impact of Subsidized Artemisinin-Based Combination Therapies Distributed Through Private Drug Shops in Rural Tanzania.

    OpenAIRE

    Sabot, OJ; Mwita, A; Cohen, JM; Ipuge, Y; Gordon, M.; Bishop, D.; Odhiambo, M; Ward, L; Goodman, C

    2009-01-01

    BACKGROUND: WHO estimates that only 3% of fever patients use recommended artemisinin-based combination therapies (ACTs), partly reflecting their high prices in the retail sector from where many patients seek treatment. To overcome this challenge, a global ACT subsidy has been proposed. We tested this proposal through a pilot program in rural Tanzania. METHODS/PRINCIPAL FINDINGS: Three districts were assigned to serve either as a control or to receive the subsidy plus a package of supporting i...

  8. Rates of asthma attacks in patients with previously inadequately controlled mild asthma treated in clinical practice with combination drug therapy: an exploratory post-hoc analysis

    OpenAIRE

    Sazonov Vasilisa; Fan Tao; Zhang Qiaoyi; Borderias Luis; Dal Negro Robert W; Guilera Magda; Taylor Stephanie D

    2009-01-01

    Abstract Background Differences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON). Methods This was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination ...

  9. Old Drugs To Treat Resistant Bugs: Methicillin-Resistant Staphylococcus aureus Isolates with mecC Are Susceptible to a Combination of Penicillin and Clavulanic Acid.

    Science.gov (United States)

    Ba, Xiaoliang; Harrison, Ewan M; Lovering, Andrew L; Gleadall, Nicholas; Zadoks, Ruth; Parkhill, Julian; Peacock, Sharon J; Holden, Matthew T G; Paterson, Gavin K; Holmes, Mark A

    2015-12-01

    β-Lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA) is mediated by the expression of an alternative penicillin-binding protein 2a (PBP2a) (encoded by mecA) with a low affinity for β-lactam antibiotics. Recently, a novel variant of mecA, known as mecC, was identified in MRSA isolates from both humans and animals. In this study, we demonstrate that mecC-encoded PBP2c does not mediate resistance to penicillin. Rather, broad-spectrum β-lactam resistance in MRSA strains carrying mecC (mecC-MRSA strains) is mediated by a combination of both PBP2c and the distinct β-lactamase encoded by the blaZ gene of strain LGA251 (blaZLGA251), which is part of mecC-encoding staphylococcal cassette chromosome mec (SCCmec) type XI. We further demonstrate that mecC-MRSA strains are susceptible to the combination of penicillin and the β-lactam inhibitor clavulanic acid in vitro and that the same combination is effective in vivo for the treatment of experimental mecC-MRSA infection in wax moth larvae. Thus, we demonstrate how the distinct biological differences between mecA- and mecC-encoded PBP2a and PBP2c have the potential to be exploited as a novel approach for the treatment of mecC-MRSA infections. PMID:26392513

  10. Acupoint-Specific, Frequency-Dependent, and Improved Insulin Sensitivity Hypoglycemic Effect of Electroacupuncture Applied to Drug-Combined Therapy Studied by a Randomized Control Clinical Trial

    Directory of Open Access Journals (Sweden)

    Rong-Tsung Lin

    2014-01-01

    Full Text Available The application of electroacupuncture (EA to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM. There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

  11. Clinical Weighting of Drug-Drug Interactions in Hospitalized Elderly.

    Science.gov (United States)

    Juárez-Cedillo, Teresa; Martinez-Hernández, Cynthia; Hernández-Constantino, Angel; Garcia-Cruz, Juan Carlos; Avalos-Mejia, Annia M; Sánchez-Hurtado, Luis A; Islas Perez, Valentin; Hansten, Philip D

    2016-04-01

    Adverse drug reactions impact on patient health, effectiveness of pharmacological therapy and increased health care costs. This investigation intended to detect the most critical drug-drug interactions in hospitalized elderly patients, weighting clinical risk. We conducted a cross-sectional study between January and April 2014; all patients 70 years or older, hospitalized for >24 hr and prescribed at least one medication were included in the study. Drug-drug interactions were estimated by combining Stockley's, Hansten and Tatro drug interactions. Drug-drug interactions were weighted using a risk-analysis method based on failure modes, effects and criticality analysis. We calculated a criticality index for each drug involved in the drug-drug interactions based on the severity of the interaction mechanism, the frequency the drug was involved in drug-drug interactions and the risk of drug-drug interactions in patients with impaired renal function. The average number of drugs consumed in the hospital was 6 ± 2.69, involving 160 active ingredients. The most frequent were as follows: Furosemide, followed by Enalapril. Of drug-drug interactions, 2% were classified as contraindicated, 14% advised against and 83% advised caution during the hospital stay. Thirty-four drug-drug interactions were assessed, of which 23 were pharmacodynamic drug-drug interactions and 12 were pharmacokinetic drug-drug interactions (1 was both). The clinical risk calculated for each drug-drug interaction included heparins + non-steroidal anti-inflammatory drugs (NSAIDs) or Digoxin + Calcium Gluconate, cases which are pharmacodynamic drug-drug interactions with agonist effect and clinical risk of bleeding, one of the most common clinical risks in the hospital. An index of clinical risk for drug-drug interactions can be calculated based on severity by the interaction mechanism, the frequency that the drug is involved in drug-drug interactions and the risk of drug-drug interactions in an

  12. Drug Facts

    Medline Plus

    Full Text Available ... Drug Abuse Hurts Other People Drug Abuse Hurts Families Drug Abuse Hurts Kids Drug Abuse Hurts Unborn Children ... a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free ...

  13. Drugs prescribed for self poisoners.

    OpenAIRE

    Prescott, L F; Highley, M S

    1985-01-01

    Of 230 adults admitted for self poisoning over two months, 153 (67%) had previously been taking a total of 309 prescribed drugs. Of these patients, 119 (78%) had been given psychotropic drugs (usually benzodiazepines), 81 (53%) obtained them on repeat prescription, and 47 (31%) had been prescribed multiple psychotropic drugs, often in seemingly illogical combinations. The use of these drugs increased progressively with age and most patients took the same drugs in overdosage as they had been p...

  14. Taking Current Antiretroviral Drugs

    Science.gov (United States)

    ... INHIBITORS INTEGRASE INHIBITORS 1. NUCLEOSIDE AND NUCLEOTIDE ANALOG REVERSE TRANSCRIPTASE INHIBITORS (NUKES) DRUG DAILY PILLS (ADULTS) HOW TO TAKE & ... Don't combine with d4T. 2. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS** (NNRTIs or NON-NUKES) DRUG DAILY PILLS (Adults)* ...

  15. Comparison of colistin monotherapy and non-colistin combinations in the treatment of multi-drug resistant Acinetobacter spp. bloodstream infections: A Multicenter retrospective analysis

    Directory of Open Access Journals (Sweden)

    Ilker Inanc Balkan

    2015-01-01

    Full Text Available Objectives: To compare the efficacy of colistin (COL monotherapy versus non-COL based combinations in the treatment of bloodstream infections (BSIs due to multidrug resistant Acinetobacter spp.(MDR-A . Materials and Methods: Retrospective data of 107 MDR-A BSI cases from 27 tertiary centers in Turkey were included. Primary End-Point: 14-day mortality. Secondary End-Points: Microbial eradication and clinical improvement. Results: Thirty-six patients in the COL monotherapy (CM group and 71 in the non-COL based combinations (NCC group were included in the study. Mean age was 59.98 ± 20 years (range: 18-89 and 50.5% were male. Median duration of follow-up was 40 days (range: 9-297. The 14-day survival rates were 52.8% in CM and 47.23% in NCC group (P = 0.36. Microbiological eradication was achieved in 69% of CM and 83% of NCC group (P = 0.13. Treatment failure was detected in 22.9% of cases in both CM and NCC groups. Univariate analysis revealed that mean age (P = 0.001, Charlson comorbidity index (P = 0.03, duration of hospital stay before MDR-A BSI (P = 0.04, Pitt bacteremia score (P = 0.043 and Acute Physiology and Chronic Health Evaluation II score (P = 0.05 were significant in terms of 14-day mortality. Advanced age (P = 0.01 and duration of hospital stay before MDR-A BSI (P = 0.04 were independently associated with 14-day mortality in multivariate analysis. Conclusion: No significant difference was detected between CM and non-COL based combinations in the treatment of MDR-A BSIs in terms of efficacy and 14-day mortality.

  16. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells.

    Science.gov (United States)

    McKeon, Aoife M; Egan, Alan; Chandanshive, Jay; McMahon, Helena; Griffith, Darren M

    2016-01-01

    We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ. PMID:27455212

  17. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Aoife M. McKeon

    2016-07-01

    Full Text Available We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70, pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ.

  18. Single-drop microextraction combined in-line with capillary electrophoresis for the determination of nonsteroidal anti-inflammatory drugs in urine samples.

    Science.gov (United States)

    García-Vázquez, Alejandro; Borrull, Francesc; Calull, Marta; Aguilar, Carme

    2016-01-01

    This study describes a method to determine nonsteroidal anti-inflammatory drugs (NSAIDs) in urine samples based on the use of single-drop microextraction (SDME) in a three-phase design as a preconcentration technique coupled in-line to capillary electrophoresis. Different parameters affecting the extraction efficiency of the SDME process were evaluated (e.g. type of extractant, volume of the microdroplet, and extraction time). The developed method was successfully applied to the analysis of human urine samples with LODs ranging between 1.0 and 2.5 μg/mL for all of the NSAIDs under study. This method shows RSD values ranging from 8.5 to 15.3% in interday analysis. The enrichment factors were calculated, resulting 27-fold for ketoprofen, 14-fold for diclofenac, 12-fold for ibuprofen, and 44-fold naproxen. Samples were analyzed applying the SDME-CE method and the obtained results presented satisfactory recovery values (82-115%). The overall method can be considered a promising approach for the analysis of NSAIDs in urine samples after minimal sample pretreatment. PMID:26530782

  19. Antibacterial Mode of Action of Cinnamomum verum Bark Essential Oil, Alone and in Combination with Piperacillin, Against a Multi-Drug-Resistant Escherichia coli Strain.

    Science.gov (United States)

    Yap, Polly Soo Xi; Krishnan, Thiba; Chan, Kok-Gan; Lim, Swee Hua Erin

    2015-08-01

    This study aimed to investigate the mechanism of action of the cinnamon bark essential oil (CB), when used singly and also in combination with piperacillin, for its antimicrobial and synergistic activity against beta-lactamase TEM-1 plasmid-conferred Escherichia coli J53 R1. Viable count of this combination showed a complete killing profile at 20 h and further confirmed its synergistic effect by reducing the bacteria cell numbers. Analysis on the stability of treated cultures for cell membrane permeability by CB when tested against sodium dodecyl sulfate revealed that the bacterial cell membrane was disrupted by the essential oils. Scanning electron microscopy observation and bacterial surface charge measurement also revealed that CB causes irreversible membrane damage and reduces the bacterial surface charge. In addition, bioluminescence expression of Escherichia coli [pSB1075] and E. coli [pSB401] by CB showed reduction, indicating the possibility of the presence of quorum sensing (QS) inhibitors. Gas-chromatography and mass spectrometry of the essential oil of Cinnamomum verum showed that trans-cinnamaldehyde (72.81%), benzyl alcohol (12.5%), and eugenol (6.57%) were the major components in the essential oil. From this study, CB has the potential to reverse E. coli J53 R1 resistance to piperacillin through two pathways; modification in the permeability of the outer membrane or bacterial QS inhibition. PMID:25381741

  20. Treatment of cystic ovaries with controlled vaginal drug release in combination with gonadotropins and prostaglandins in dairy cows under Egyptian conditions

    Directory of Open Access Journals (Sweden)

    H.A. Amer

    2008-02-01

    Full Text Available Traditional methods of oestrus synchronization developed over the past 60 years have involved controlling estrous cycle length by luteolytic drugs. The use of controlled internal drug release (CIDR devices is now well accepted throughout the world to treat some diseases. This study aimed to: a investigate the ovarian and endocrine responses associated with the treatment of cystic ovarian follicles with gonadotropin (GnRH and prostaglandin (PGF2α +/- Progesterone-CIDR placement; b determine pregnancy establishment following synchronization and timed artificial insemination in cows suffering from cystic ovarian follicles. The ovarian cysts were typed based on the rectal and ultrasonic examination (B-mode System; Pie-Medical Scanner-240 with 6-8 MHz linear probe into follicular, luteinized and persistent cysts. Two schedules of treatment were designed, in schedule-A, 15 cows with follicular (n=7, luteinized (n=3 and persistent (n=5 cysts were used. The cows received 2 injections of 100 ug GnRH (9 days interval with 25 mg PGF2α administered 7 days after 1st GnRH dose. In schedule-B, 14 cows with follicular (n=6, luteinized (n=3 and persistent (n=5 cysts were used. The cows administered GnRH and CIDR concurrently, then 25 mg PGF2α 7 days later. The CIDR was removed 2 days after PGF2α. The cows were inseminated 16 hours after 2nd GnRH dose. Blood samples were collected from the jugular vein during the course of 2 schedules to assay the progesterone and estradiol. In schedule-A, 57.1 %, 33.3 % and 40 % of follicular, luteinized and persistent cysts were ovulated after the 1st GnRH injection, while a total of 100 %, 66.7 % and 100 % were ovulated after the 2nd GnRH dose. The cows with follicular cysts appeared the highest rate of pregnancy (57.1 % followed by the luteinized and persistent cysts (33.3 % and 40 %. Of a total 15 cystictreated cows, 7 were confirmed pregnant (46.7 %. The concentration of progesterone was significantly higher at 1st Gn

  1. Efficacy analysis of two drugs consisting platinum combined with first-line chemotherapeutics regimens on 117 elderly patients with advanced non-small cell lung carcinoma

    Directory of Open Access Journals (Sweden)

    Li-li ZHANG

    2013-09-01

    Full Text Available Objective To investigate the therapeutic effects of Gemcitabine(GEM, Vinorelbine(NVB,Paclitaxel(TAX and other first-line chemotherapeutics plus platinum containing drugs on the elderly patients with advanced non-small cell lung cancer(NSCLC who had undergone surgery, and analyze the clinicopathological factors influencing the prognosis. Methods One hundred and seventeen advanced NSCLC patients aged 60 or over were treated with GP(GEM+platinum, or NP(NVB+platinum, or TP(TAX+platinum, or other first-line chemotherapeutics plus platinum(OCP after surgery, and their clinical data were then retrospectively studied to look for the relationship of patients' prognosis to clinicopathological factors(gender, operation methods, pathologicaltypes, differentiation, clinical stages.The survival curve was plotted with Kaplan-Meier method, hypothesis test was performed by log-rank, and the independent prognostic factors were screened with Cox proportional hazards regression model. Results Theone-, three- and five-year survival rates of the 117 patients were 47.23%,17.52% and 8.05%, respectively. The progression free survival(PFS of GP, NP, TP and OCP groups were 6.0, 5.2, 6.1 and5.5 months(P>0.05, respectively. The median progression free survival was 5.7 months. Univariate and multivariate analysis showed that the differentiated degrees and clinical stages of elderly NSCLC patients were the independent prognostic factors. Conclusions Clinicopathological factors(differentiated degree andclinical stages are closely related to one-, three- and five-year survival rates of advanced NSCLC in elderly patients who received treatment of first-line chemotherapeutics plus platinum. However, the efficacy ofGP, NP, TP or OCP shows no significant difference.

  2. Assessment of the combined approach of N-alkylation and salt formation to enhance aqueous solubility of tertiary amines using bupivacaine as a model drug

    DEFF Research Database (Denmark)

    Nielsen, Anders Bach; Frydenvang, Karla Andrea; Liljefors, Tommy;

    2005-01-01

    tertiary amine (up to a factor of 3200 at pH 8). A moderate reduction in solubility with increasing length of the alkyl chain was observed for the iodide salts of the N-alkylated bupivacaine derivatives. In case of the N-methyl-bupivacaine derivative variation of the counterion had a significant impact......Quaternary prodrug types of poorly water-soluble tertiary amines have been shown to exhibit significantly enhanced solubilities as compared to the parent amine. In the present study the combined effect of N-alkylation and salt formation to enhance aqueous solubility of tertiary amines have been...... investigated using bupivacaine as a model compound. X-ray structure analyses of selected salts were included to investigate the potential existence of correlations between salt solubility and crystal packing modes. Alkyl groups were methyl, ethyl, propyl, and butyl and the derivatives were isolated...

  3. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  4. Development and application of a UPLC-MS/MS method for simultaneous determination of fenofibric acid and berberine in rat plasma: application to the drug-drug pharmacokinetic interaction study of fenofibrate combined with berberine after oral administration in rats.

    Science.gov (United States)

    Li, Guofei; Yang, Fan; Liu, Mei; Su, Xianying; Zhao, Mingming; Zhao, Limei

    2016-07-01

    With the purpose of carrying out pharmacokinetic interaction studies ofnberberine (BBR) and fenofibrate (FBT), an UPLC-MS/MS method has been developed and validated. The analytes, BBR and fenofibric acid (FBA, metabolite of FBT) and the internal standard, tetrahydropalmatine, were extracted with dichloromethane-diethyl ether (3:2, v/v) and separated on an Agilent Eclipse XDB C18 column using a mobile phase composed of acetonitrile and water. With positive ion electrospray ionization, the analytes were monitored on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. Linear calibration curves were obtained over the concentration ranges of 0.1-100.0 ng/mL for BBR and 10.0-50,000.0 ng/mL for FBA. For BBR and FBA, the intra- and inter-day precisions were 85.6%, and those of FBA at three concentrations of 20.0, 2500.0, 40,000.0 ng/mL were >87.9%. Consequently, the proposed method was applied to the pharmacokinetic interaction study of FBT combined with BBR after oral administration in rats and was proved to be sensitive, specific and reliable to analyze BBR and FBA in biological samples simultaneously. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26577601

  5. Biodistribution study of [{sup 99m}Tc] TRODAT-1 alone or combined with other dopaminergic drugs in mice with macroautoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, J.J. E-mail: jjhwang@ym.edu.tw; Liao, M.H.; Yen, T.C.; Wey, S.P.; Lin, K.J.; Pan, W.H.T.; Chen, J.C.; Ting, G

    2002-07-01

    A {sup 99m}Tc labeled tropane derivative, [{sup 99m}Tc] TRODAT-1 (2{beta}-((N,N'-bis(2-mercaptoethyl) ethylene diamino)methyl), 3{beta}-(4-chlorophenyl) tropane), is a potential dopamine transporter (DAT) imaging agent for the central nervous system. To better understand the binding localization of [{sup 99m}Tc] TRODAT-1 both in the brain and the body, whole-body macroautoradiography (WBAR) was used in this study. The effect of DAT competing drugs, such as levadopa (L-DOPA), N-methyl-2{beta}-carbomethoxy-3{beta}-(4fluorophenyl)tropane (CFT, WIN 35,428) and methylphenidate, on the biodistribution of [{sup 99m}Tc] TRODAT-1 were also included in this study. Doses of 150 MBq [{sup 99m}Tc] TRODAT-1 were injected into normal male ICR mice through the caudal veins. For comparison, mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), L-DOPA, methylphenidate and CFT, respectively, were also investigated under the similar protocols. One and a half hours after [{sup 99m}Tc] TRODAT-1 injection, the mice were sacrificed. Whole-body autoradiography was performed immediately after sacrifice. Both frontal and sagittal sections showed that the liver and mucosa of stomach had the highest uptake of [{sup 99m}Tc] TRODAT-1. Other binding sites included the periphery of the spinal cord and the epithelium of the intestine. In the brain, autoradiographic imaging obtained from frontal sections showed symmetrical uptakes of [{sup 99m}Tc] TRODAT-1 in bilateral striata. Remaining binding sites include olfactory bulbs, thyroid gland, and salivary gland. The autoradiographic imaging obtained from sagittal sections showed a similar biodistribution. Mice treated with MPTP or L-DOPA showed no significant difference in the uptake of [{sup 99m}Tc] TRODAT-1 in bilateral striata, as compared to those of the control. In CFT or methylphenidate-treated mice, DAT binding sites were almost completely inhibited. These data showed that [{sup 99m}Tc] TRODAT-1 has potential clinical use

  6. Prescription Drugs

    Science.gov (United States)

    ... Us Search Search close Teens Teachers Parents Drugs & Health Blog NDAFW Enter Search Term(s): Teens / Drug Facts / Prescription Drugs Prescription Drugs Print What Is Prescription Drug Abuse? Also known as: Opioids: Hillbilly heroin, oxy, OC, oxycotton, percs, happy pills, vikes Depressants: ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... Work? Types of Drug Treatment What Is a Relapse? Find Treatment/Rehab Resources Friends and Family Can Help Prevent Drug Abuse Help Children and Teens Stay Drug-Free Talking to Kids About Drugs: What To Say if You Were Once Addicted Drug Abuse Prevention Phone ... English ...

  8. Beetroot-Carrot Juice Intake either Alone or in Combination with Antileukemic Drug 'Chlorambucil' As A Potential Treatment for Chronic Lymphocytic Leukemia.

    Science.gov (United States)

    Shakib, Marie-Christine R; Gabrial, Shreef G N; Gabrial, Gamal N

    2015-06-15

    Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes. Patients with leukemia often seek unconventional treatments not prescribed by hematologist in order to improve their cancer treatment outcome or to manage symptoms. In the present report, a 76-year-old patient was diagnosed with B-cell chronic lymphocytic leukemia (B-CLL). Beetroot-carrot juice is used as a complementary and or/alternative therapy used in conjunction with conventional leukemic treatment (chlorambucil) that has been a standard first-line chemotherapeutic agent for patients with CLL and known to have serious and undesirable side-effects. After one month and 15 days of administration of beetroot-carrot juice therapy, the patient had improved appetite, a sense of general well-being and increased vigor daily activities. Furthermore, beetroot-carrot juice was used as an adjuvant to chlorambucil resulted in a substantial reduction in leukocytes and lymphocytes count in peripheral blood and improvement in the relevant biochemical parameters. Beetroot-carrot juice can be used as an effective treatment for CLL alone or in combination with chlorambucil when taken orally with regular diet on daily basis. PMID:27275246

  9. Beetroot-Carrot Juice Intake either Alone or in Combination with Antileukemic Drug ‘Chlorambucil’ As A Potential Treatment for Chronic Lymphocytic Leukemia

    Science.gov (United States)

    Shakib, Marie-Christine R.; Gabrial, Shreef G. N.; Gabrial, Gamal N.

    2015-01-01

    Chronic lymphocytic leukemia (CLL) is one of the chronic lymphoproliferative disorders (lymphoid neoplasms). It is characterized by a progressive accumulation of functionally incompetent lymphocytes. Patients with leukemia often seek unconventional treatments not prescribed by hematologist in order to improve their cancer treatment outcome or to manage symptoms. In the present report, a 76-year-old patient was diagnosed with B-cell chronic lymphocytic leukemia (B-CLL). Beetroot-carrot juice is used as a complementary and or/alternative therapy used in conjunction with conventional leukemic treatment (chlorambucil) that has been a standard first-line chemotherapeutic agent for patients with CLL and known to have serious and undesirable side-effects. After one month and 15 days of administration of beetroot-carrot juice therapy, the patient had improved appetite, a sense of general well-being and increased vigor daily activities. Furthermore, beetroot-carrot juice was used as an adjuvant to chlorambucil resulted in a substantial reduction in leukocytes and lymphocytes count in peripheral blood and improvement in the relevant biochemical parameters. Beetroot-carrot juice can be used as an effective treatment for CLL alone or in combination with chlorambucil when taken orally with regular diet on daily basis. PMID:27275246

  10. Beetroot-Carrot Juice Intake either Alone or in Combination with Antileukemic Drug 'Chlorambucil' As A Potential Treatment for Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Marie-Christine R. Shakib

    2015-06-01

    Full Text Available Chronic lymphocytic leukemia (CLL is one of the chronic lymphoproliferative disorders (lymphoid neoplasms. It is characterized by a progressive accumulation of functionally incompetent lymphocytes. Patients with leukemia often seek unconventional treatments not prescribed by hematologist in order to improve their cancer treatment outcome or to manage symptoms. In the present report, a 76-year-old patient was diagnosed with B-cell chronic lymphocytic leukemia (B-CLL. Beetroot-carrot juice is used as a complementary and or/ alternative therapy used in conjunction with conventional leukemic treatment (chlorambucil that has been a standard first-line chemotherapeutic agent for patients with CLL and known to have serious and undesirable side-effects. After one month and 15 days of administration of beetroot-carrot juice therapy, the patient had improved appetite, a sense of general well-being and increased vigor daily activities. Furthermore, beetroot-carrot juice was used as an adjuvant to chlorambucil resulted in a substantial reduction in leukocytes and lymphocytes count in peripheral blood and improvement in the relevant biochemical parameters.  Beetroot-carrot juice can be used as an effective treatment for CLL alone or in combination with chlorambucil when taken orally with regular diet on daily basis.

  11. Farnesiferol c induces apoptosis via regulation of L11 and c-Myc with combinational potential with anticancer drugs in non-small-cell lung cancers.

    Science.gov (United States)

    Jung, Ji Hoon; Kim, Moon Joon; Lee, Hyemin; Lee, Jihyun; Kim, Jaekwang; Lee, Hyun Joo; Shin, Eun Ah; Kim, Yoon Hyeon; Kim, Bonglee; Shim, Bum Sang; Kim, Sung-Hoon

    2016-01-01

    Though Farnesiferol c (FC) has been reported to have anti-angiogenic and antitumor activity, the underlying antitumor mechanism of FC still remains unclear. Thus, in the present study, we investigated the apoptotic mechanism of FC in human H1299 and H596 non-small lung cancer cells (NSCLCs). FC significantly showed cytotoxicity, increased sub-G1 accumulation, and attenuated the expression of Bcl-2, Bcl-xL, Survivin and procaspase 3 in H1299 and H596 cells. Furthermore, FC effectively suppressed the mRNA expression of G1 arrest related genes such as Cyclin D1, E2F1 transcription factor and CDC25A by RT-PCR. Interestingly, FC inhibited the expression of c-Myc, ribosomal protein L11 (L11) and nucleolin (NCL) in H1299 and H596 cells. Of note, silencing of L11 by siRNA transfection enhanced the expression of c-Myc through a negative feedback mechanism, while c-Myc knockdown downregulated L11 in H1299 cells. Additionally, combined treatment of FC and puromycin/doxorubicin promoted the activation of caspase 9/3, and attenuated the expression of c-Myc, Cyclin D1 and CDK4 in H1299 cells compared to single treatment. Taken together, our findings suggest that FC induces apoptosis and G1 arrest via regulation of ribosomal protein L11 and c-Myc and also enhances antitumor effect of puromycin or doxorubicin in NSCLCs. PMID:27231235

  12. Image Guided Biodistribution of Drugs and Drug Delivery

    Directory of Open Access Journals (Sweden)

    Hong Ding, Fang Wu

    2012-01-01

    Full Text Available Image guided technique is playing an increasingly important role in the investigation of the biodistribution and pharmacokinetics of drugs or drug delivery systems. The application of these new materials and techniques with combined properties of diagnosis and therapy can benefit the development of targeted drug delivery system and modern personalized medicine This special issue provides an up-to-date collection of original research articles and review on the development of novel targeted drug and drug delivery systems combining with non-invasive image guided techniques for chemotherapeutic reagents or DNA delivery.

  13. Systematic review and network meta-analysis of combination and monotherapy treatments in disease-modifying antirheumatic drug-experienced patients with rheumatoid arthritis: analysis of American College of Rheumatology criteria scores 20, 50, and 70

    Directory of Open Access Journals (Sweden)

    Orme ME

    2012-12-01

    Full Text Available Michelle E Orme,1 Katherine S MacGilchrist,2 Stephen Mitchell,2 Dean Spurden,3 Alex Bird31Icera Consulting, Swindon, Wiltshire, UK; 2Systematic Review Department, Abacus International, Bicester, Oxfordshire, UK; 3Pfizer UK Limited, Tadworth, Surrey, UKBackground: Biologic disease-modifying antirheumatic drugs (bDMARDs extend the treatment choices for rheumatoid arthritis patients with suboptimal response or intolerance to conventional DMARDs. The objective of this systematic review and meta-analysis was to compare the relative efficacy of EU-licensed bDMARD combination therapy or monotherapy for patients intolerant of or contraindicated to continued methotrexate.Methods: Comprehensive, structured literature searches were conducted in Medline, Embase, and the Cochrane Library, as well as hand-searching of conference proceedings and reference lists. Phase II or III randomized controlled trials reporting American College of Rheumatology (ACR criteria scores of 20, 50, and 70 between 12 and 30 weeks' follow-up and enrolling adult patients meeting ACR classification criteria for rheumatoid arthritis previously treated with and with an inadequate response to conventional DMARDs were eligible. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using fixed and random-effects, logit-link models fitted to the binomial ACR 20/50/70 trial data.Results: The systematic review identified 10,625 citations, and after a review of 2450 full-text papers, there were 29 and 14 eligible studies for the combination and monotherapy meta-analyses, respectively. In the combination analysis, all licensed bDMARD combinations had significantly higher odds of ACR 20/50/70 compared to DMARDs alone, except for the rituximab comparison, which did not reach significance for the ACR 70 outcome (based on the 95% credible interval. The etanercept combination was

  14. Synergistic iontophoretic drug delivery of risedronate sodium in combination with electroporation and chemical penetration enhancer: In-vitro and in-vivo evaluation

    Directory of Open Access Journals (Sweden)

    Swaroop R Lahoti

    2015-01-01

    Full Text Available In the present investigation iontophoretic permeation of risedronate sodium (RS through optimized gel based formulation was evaluated with respect to various electrical parameters like Current density and type of current. The study also involved enhancement the iontophoretic permeation of RS in combination with electroporation and chemical penetration enhancers with its in-vivo Pharmacokinetic evaluation. The permeation studies were carried through the human cadaver skin by using modified Franz diffusion cell and microcontroller based devices for iontophoresis and electroporation developed in the laboratory. In-vivo Pharmacokinetic studies were carried out in hairless rats. One way ANOVA followed by Tukey-Kramer test for multiple comparisons. The permeation of RS was significantly increased with iontophoresis at 0.5 mA/Cm 2 current density. The iontophoretic permeation was found depend on current density and ON:OFF ratio. The pulsatile current resulted in high permeation than continuous current. Maximum permeation was obtained at 0.5 mA/cm 2 with 1:1 pulsed current. When iontophoresis was coupled with chemical penetration enhancers and electroporation for 100 ms at 220V, synergistic enhancement in permeation was observed with shortened lag time and high flux. The required flux was achieved with area of application 1.55 cm 2 . In-vivo studies in hairless rats revealed high C max, low t max and increased area under the curve with electroporation, followed by iontophoresis indicated increased bioavailability. Relative bio-availability was 4.6 when calculated in comparison to passive studies.

  15. Hyperbaric Oxygen Combined With Drug Treatment of Sudden Deafness%高压氧联合药物治疗突发性耳聋临床对比研究

    Institute of Scientific and Technical Information of China (English)

    王栋武

    2015-01-01

    目的:重点探索高压氧联合药物应用于治疗突发性耳聋的有效性。方法挑选的研究对象是86例突发性耳聋患者,将患者分成两组,采用不同的方法治疗。结果对照组的有效率仅仅达到74.42%,显著低于观察组的97.67%。对照组的满意度较低,仅可达到72.09%,显著低于观察组的97.67%。结论高压氧联合药物应用于治疗突发性耳聋的有效性较高,值得推荐。%Objective To explore the effectiveness of hyperbaric oxygen combined with the focus of drug used in the treatment of sudden deafness. Methods The subjects were selected 86 cases of sudden deafness patients, the patients were divided into two groups, using different methods of treatment. Results The response rate in the control group reached only 74.42 percent, signiifcantly lower than the 97.67%in the observation group. Lower satisfaction with the control group, only up to 72.09%, signiifcantly lower than the 97.67% in the observation group. Conclusion The high effectiveness of hyperbaric oxygen combined with drugs used in the treatment of sudden deafness, is recommended.

  16. Club Drugs

    Science.gov (United States)

    ... Club drugs are also sometimes used as "date rape" drugs, to make someone unable to say no to or fight back against sexual assault. Abusing these drugs can cause serious health problems and sometimes death. ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Health Drug Abuse Hurts Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen ... of Health (NIH) , the principal biomedical and behavioral research agency of the United States Government. NIH is ...

  18. Club Drugs

    Science.gov (United States)

    ... Science Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the ... Learn more Statistics and Trends Swipe left or right to scroll. Monitoring the Future Study: Trends in ...

  19. Drug Facts

    Medline Plus

    Full Text Available ... Weed, Pot) Facts Meth (Crank, Ice) Facts Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What ... About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800- ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) ... Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800-662- ...

  1. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as gingko and blood thinners ...

  2. Drug Resistance

    Science.gov (United States)

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  3. 高压氧配合药物治疗突发性耳聋作用观察%To observe the effect of hyperbaric oxygen combined with drugs in the treatment of sudden deafness

    Institute of Scientific and Technical Information of China (English)

    金峰松; 潘统快

    2015-01-01

    目的:分析在临床对于突发性耳聋患者实施治疗过程中高压氧配合药物的治疗效果。方法收集在我院进行治疗的40例突发性耳聋患者,将患者分为观察组以及对照组,各20例。对照组患者使用常规药物治疗,观察组患者使用高压氧配合药物治疗的方法进行治疗。结果两组患者均能够取得一定的治疗效果,但观察组患者的临床治疗有效率明显高于对照组患者的临床治疗有效率,差异显著。结论对于突发性耳聋患者实施治疗的过程中使用高压氧配合药物治疗的形式能够取得更好的治疗效果,在临床上值得推广应用。%Objective: To analyze the clinical implementation of drug for patients with sudden deafness treatment with hy-perbaric oxygen treatment process. Methods: Collected 40 cases of sudden deafness patients in our hospital, the patients were di-vided into observation group and control group, 20 cases in each. The control group was treated with routine drug treatment, the observation group were treated with hyperbaric oxygen therapy with drug treatment.Results: Two groups of patients were able to achieve a certain therapeutic effect, but the clinical observation of patients in the treatment group, the effective rate was signifi-cantly higher than the control group in the treatment of patients with clinical efficiency, significant difference.Conclusion:The implementation of the treatment process of patients with sudden deafness with hyperbaric oxygen combined with drug treatment can achieve better therapeutic effect, worthy of clinical application.

  4. 高压氧综合治疗突发性耳聋的疗效评价%An Effective Appraisal of Hyperbaric Oxygen Combined with Drugs Therapy for Sudden Deafness

    Institute of Scientific and Technical Information of China (English)

    胡丽娜; 姚昭文; 杜玉琴

    2001-01-01

    Objective:To investigate the effect of hyperbaricoxygen(HBO)combined with drugs therapy for sudden deafness(SD).Methods:Twenty-six patients(31ears)with SD were exposed to HBO[pure oxygen breathing at 250 kPa(2.5ATA)absolute for 30min,twice,with a 10 min air breathing breath in the chamber,once a day],meanwhile they were also given commonly used drugs(energy mixture,injectio salvia miltiorrhiza Co, dextran 40,vitamin B group and corticoids)for(17.5±6.73)days.Thirty patients(33 ears)for comparison(non-HBO group)were treated only by the above-mentioned drug without HBO.Results:HBO group:7 ears were cured,6 ears markedly improved,10 ears improved;non-HBO group:5 ears were cured,4 ears markedly improved,7 ears improved.The overall effective rate in HBO group(72.4%)was higher than that in non-HBO group(48.5%)(χ2=4.438,P<0.025).Conclusion:The therapeutic effect of HBO combined with drugs for SD is significantly better than that of simple drug treatment without HBO.%目的:探讨高压氧联合药物治疗突发性耳聋(突聋)的疗效。方法:26例(31耳)突发性耳聋患者(HBO组)在250kPa(2.5ATA)压力下吸纯氧30min共2次,中间吸空气10min,每日1次,同时配合能量合剂、复方丹参液、低分子右旋糖酐、B族维生素、皮质激素等药物治疗,平均疗程(17.5±6.73)天。将本组疗效与单纯使用同类药物治疗的30例(33耳)突聋(非HBO组)进行比较。结果:HBO组痊愈7耳,显效6耳,有效10耳,总有效率72.4%;非HBO组痊愈5耳,显效4耳,有效7耳,总有效率48.5%,两组比较χ2=4.438,P<0.025。结论:HBO联合药物治疗突聋的效果明显优于单纯药物治疗。

  5. 高能窄谱光子联合药物治疗外阴湿疹的临床研究%Clinical Research of High Energy Narrow Spectrum Photons Combined with Drug Therapy on the treatment of Vulva Eczema

    Institute of Scientific and Technical Information of China (English)

    刘珉名; 董玲; 邬英

    2015-01-01

    Objective To evaluate the effect of High Energy Narrow Spectrum Photons Combined with Drug Therapy on the treatment of Vulva Eczema. Methods 86 patients with Vulva Eczema who came to the dermatological department of our hospital during January 2013 to June 2014 were involved and divided into two groups randomly. In the control group, patients were treated with conventional drugs,while in the experimental group, conventional drugs combined with Carnation Photons therapy. Clinical efficacy and adverse effect between two groups were evaluated after 3 weeks of treatment. Results The total effective rate in the experimental group and control group was 100%and 93.0%, respectively. The treatment effect in the experimental group was significantly better than that in the control group, and the difference was statistically significant (P <0.05). The average cure time in the experimental group and the control group were (10.2 ±3.6) days, (13.1 ±5.4) days. The cure time of the experimental group was significantly less than the control group,and the difference was statistically significant (P<0.05). No obvious adverse effect was observed in both groups. Conclusion The effect of High Energy Narrow Spectrum Photons Combined with Drug Therapy in the treatment of Vulva Eczema is satisfactory. And this treatment method is easy operated with less adverse effect, and worthy to be recommended in the clinical application.%目的:探讨高能窄谱光子联合药物治疗外阴湿疹的临床效果。方法选取2013年1月~2014年6月我院皮肤科门诊治疗的外阴湿疹患者86例,对照组患者采取常规药物治疗,实验组在对照组基础上加用Carnation光子治疗仪进行治疗。治疗三周后对两组患者的疗效和不良反应进行评价。结果实验组患者治疗总有效率为100.0%,对照组患者治疗总有效率为93.0%。实验组患者的治疗效果明显优于对照组,差异有统计学意义(P<0.05)。实

  6. Combined effect of the essential oil from Chenopodium ambrosioides and antileishmanial drugs on promastigotes of Leishmania amazonensis Efeito combinado do óleo de essência de Chenopodium ambrosioides e drogas anti-leishmaniose nos promastigotas de Leishmania amazonensis

    Directory of Open Access Journals (Sweden)

    Lianet Monzote

    2007-08-01

    Full Text Available To date, there are no vaccines against Leishmania, and chemotherapy remains the mainstay for the control of leishmaniasis. The drugs of choice used for leishmaniasis therapy are significantly toxic, expensive and with a growing frequency of refractory infections. Because of these limitations, a combination therapy is the better hope. This work demonstrates that the essential oil from Chenopodium ambrosioides shows a synergic activity after incubation in conjunction with pentamidine against promastigotes of Leishmania amazonensis. However, an indifferent effect has been found for combinations of meglumine antimoniate or amphotericin B and the essential oil.Até hoje não temos vacina contra a Leishmania e a quimioterapia é a indicação para o controle desta doença. Os remédios que hoje utilizamos são tóxicos e muito caros e além disso o resultado não é sempre o desejado. Por isso, uma terapia de combinação é a melhor opção. Este trabalho mostra que o óleo de essência de C. ambrosioides tem atividade sinérgica junto com a pentamidina sobre os promastigotas de L. amazonensis, diferente do resultado da combinação de antimônio de meglumine e anfotericina B e o óleo de essência.

  7. 曲妥珠单抗联合不同化疗药物治疗乳腺癌的临床疗效%An Analysis of Clinical Efficacy on Trastuzumab Combined with Other Chemotherapy Drugs to Treat Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    杨立平

    2015-01-01

    [Objective]To study the clinical effect of trastuzumab therapy with the combination of chemo-therapy drugs for treatment of breast cancer.[Methods]97 cases of patients with breast cancer undergoing trastuzumab combined with different chemotherapy drugs in our hospital were collected from January 2007 to January 2010,among which 30 cases (Group A)were treated with trastuzumab only,33 cases(Group B)with trastuzumab plus vinorelbine ,and 34 cases (Group C)with trastuzumab combined with paclitaxel .A retro-spective analysis of the effects of different treatment programs was undertaken on therapeutic efficacy,toxic and adverse effects and patient survival situation.[Results]Total effective of Group B for the treatment of pa-tients with breast cancer is 36.36% with its disease control rate 78.78%;Total effective of Group C was 32.35% ,and its disease control rate 67.65%;The total clinical effectives and disease control rates of the two groups were significantly higher than those of Group A,with obvious difference there exits (P 0.05 )[Conclusion]Combination therapy of trastuzumab with different chemotherapy drugs for treatment of breast cancer is clinically superior to that of trastuzumab alone.The toxic and adverse effects herewith are well tolerated.Thus ,it is worth of clinical application.%【目的】探讨曲妥珠单抗联合不同化疗药物治疗乳腺癌的临床疗效。【方法】收集整理2007年1月至2010年1月期间在本院接受曲妥珠单抗治疗的97例乳腺癌患者的临床资料,其中单用曲妥珠单抗(A组)治疗的30例,曲妥珠单抗联合长春瑞滨方案(B 组)治疗者33例,曲妥珠单抗联合紫杉醇方案(C)治疗者34例。比较分析不同方案的治疗效果、治疗期间的毒副反应及患者生存情况。【结果】B 组治疗乳腺癌患者的总有效为36.36%,疾病控制率为78.78%;C组治疗乳腺癌患者的总有效率为32.35%,疾病控制率为67.65%;两组临床总有效率及

  8. Drug Abuse

    Science.gov (United States)

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... text to you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol ... of the drug. "Max" was addicted to prescription drugs. The addiction slowly took over his life. I need different ...

  10. Combinação de fármacos na abordagem das dislipidemias: associação entre estatinas e niacina Combination of drugs: statins and niacin

    Directory of Open Access Journals (Sweden)

    Jairo Lins Borges

    2005-10-01

    Full Text Available A combinação de estatinas com niacina se apresenta como uma atraente associação, na presença de dislipidemia mista com níveis de HDL baixo, quando monoterapia é insuficiente para o alcance das metas lipídicas. Benefícios clínicos foram observados com a combinação de estatinas com niacina nos estudos FATS, HATS e ARBITER 2, mostrando atenuação no desenvolvimento da aterosclerose e/ou redução de eventos coronários, acompanhados de alterações lipídicas favoráveis. Em geral, esta combinação é bem tolerada. Recomenda-se monitoração adequada das enzimas hepáticas e muscular e, ainda, titulação cuidadosa de cada uma das drogas combinadas.Combination of statins with niacin appears to be an attractive association, in the presence of mixed dyslipidemia with low HDL-c levels, when monotherapy is insufficient to achieve target lipid levels. Clinical benefits were observed by the combination of statins with niacin in the FATS, HATS and ARBITER 2 trials, showing attenuation of atherosclerosis development and/or reduction in coronary events following favorable lipid changes. In general, this combination can be well-tolerated. Recommendations for appropriate monitoring of liver and muscle enzymes are important to reduce the rate of side effects. In addition, careful titration of each drug is recommended.

  11. 传统中药与阿莫西林联合治疗压疮的临床研究%Clinical Study of a Traditional Chinese Drug Combined with Amoxicillin in Treating Bedsore

    Institute of Scientific and Technical Information of China (English)

    郝玉梅; 刘如月

    2015-01-01

    To Study a traditional Chinese drug Combined with Amoxicillin in treating I - IV Bedsore ,the paper used the combined therapy in treating 60 cases of Bedsore in different stages during 2011 - 2015 .Effective rate in the treatment group was 97 .1% and ulceration healing time was shorter .T he conclusion is that the combined therapy has significant effect and low cost in treating bedsore in different stages and it’s worth popularizing in clinic .%文章主要研究传统中药去腐生肌的原理,探索联合阿莫西林制成中、西药配方治疗各期压疮疗的疗效.对商丘医学高等专科学校附院2011年~2015年收治的60例130处不同分期的压疮,随机分成对照组30例60处压疮和治疗组各30例70处压疮,对照组采用常规方法治疗和护理,治疗组按压疮的分期分别采用自制中、西药联合配方进行治疗.结果显示,治疗组30例患者70处Ⅰ~Ⅳ期压疮有效率高达97.1%以上,并且能显著缩短溃疡愈合时间.结论:中、西药联合配方对各期压疮均有显著效果且费用低,值得在临床推广.

  12. Analgesic drugs

    OpenAIRE

    Kerec Kos, Mojca

    2015-01-01

    In the management of pain analgesic drugs are chosen regarding the intensity and type of pain. The selection of analgesic drug depends on pharmacokinetic properties of the drug and available pharmaceutical dosage forms. Beside non-opioid analgesics (non-steroidal antiinflammatory drugs, acetaminophen), opioid analgesic drugs have an important role in the treatment of pain. Pri zdravljenju bolečine izberemo analgetik glede na jakost in vrsto bolečine. Na izbiro ustreznega analgetika vplivaj...

  13. Hybrid nanostructured drug carrier with tunable and controlled drug release

    International Nuclear Information System (INIS)

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic–organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: ► The novel synthesis of a hybrid nanostructured drug carrier is described. ► The drug carrier exhibits high drug loading ability and is physically stable. ► The high drug release is ascribed to a cavitation-type process.

  14. Curative effect observation of antihypertensive drugs combined with diet in the treatment of hypertension%降压药物联合饮食治疗高血压的疗效观察

    Institute of Scientific and Technical Information of China (English)

    廖镀金

    2014-01-01

    Objective:To explore the curative effect of antihypertensive drugs combined with diet in the treatment of hypertension. Methods:216 patients with hypertension were selected from June 2011 to June 2013.They were divided into the observation group and the control group with 108 cases in each group according to random number table method.The observation group and the control group were treated with antihypertensive drugs,and the observation group added diet therapy,including health propaganda, giving up smoking and drinking,dietary recommendations and so on.After 4 months of treatment,we measured the blood pressure and evaluated the clinical efficacy of two groups of patients.Results:The differences of systolic pressure and diastolic pressure of the observation group and the control group were statistically significant(P<0.05).The systolic pressure and diastolic pressure of the observation group were decreased significantly.Patients in the observation group compared with the control group,efficiency and compliance rate were increased significantly(P<0.05).Conclusion:The combination of diet therapy and hypertension standardized drug treatment can better achieve the purpose of the treatment of hypertension,and diet therapy can be used as a good supplement and auxiliary therapy for hypertension standardized drug treatment.%目的:观察降压药物联合饮食治疗高血压的临床疗效。方法:2011年6月-2013年6月收治高血压患者216例,按照随机数字表的方法分为观察组和对照组,各108例。观察组和对照组患者使用降压药物治疗,观察组进一步使用饮食治疗方案,包括健康宣传、戒烟戒酒、膳食推荐等。治疗4个月后对两组患者的血压进行重复测量,对临床疗效进行评价。结果:观察组和对照组患者的收缩压及舒张压差异均有统计学意义(P<0.05),观察组的收缩压及舒张压显著较低,观察组患者与对照组相比较,有效率及达标率

  15. Drug-induced renal disorders.

    Science.gov (United States)

    Ghane Shahrbaf, Fatemeh; Assadi, Farahnak

    2015-01-01

    Drug-induced nephrotoxicity are more common among infants and young children and in certain clinical situations such as underlying renal dysfunction and cardiovascular disease. Drugs can cause acute renal injury, intrarenal obstruction, interstitial nephritis, nephrotic syndrome, and acid-base and fluid electrolytes disorders. Certain drugs can cause alteration in intraglomerular hemodynamics, inflammatory changes in renal tubular cells, leading to acute kidney injury (AKI), tubulointerstitial disease and renal scarring. Drug-induced nephrotoxicity tends to occur more frequently in patients with intravascular volume depletion, diabetes, congestive heart failure, chronic kidney disease, and sepsis. Therefore, early detection of drugs adverse effects is important to prevent progression to end-stage renal disease. Preventive measures requires knowledge of mechanisms of drug-induced nephrotoxicity, understanding patients and drug-related risk factors coupled with therapeutic intervention by correcting risk factors, assessing baseline renal function before initiation of therapy, adjusting the drug dosage and avoiding use of nephrotoxic drug combinations. PMID:26468475

  16. Quality of Artemisinin-Based Combination Formulations for Malaria Treatment: Prevalence and Risk Factors for Poor Quality Medicines in Public Facilities and Private Sector Drug Outlets in Enugu, Nigeria

    Science.gov (United States)

    Kaur, Harparkash; Allan, Elizabeth Louise; Mamadu, Ibrahim; Hall, Zoe; Ibe, Ogochukwu; El Sherbiny, Mohamed; van Wyk, Albert; Yeung, Shunmay; Swamidoss, Isabel; Green, Michael D.; Dwivedi, Prabha; Culzoni, Maria Julia; Clarke, Siân; Schellenberg, David; Fernández, Facundo M.; Onwujekwe, Obinna

    2015-01-01

    Background Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. Methods ACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. Results Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. Conclusion Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained

  17. Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria.

    Directory of Open Access Journals (Sweden)

    Harparkash Kaur

    Full Text Available Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296 of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs in Enugu metropolis, Nigeria, and compared the resulting quality estimates.ACAs were purchased using three sampling approaches--convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified.Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200, mystery (n=1,919 and overt (n=905 approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified and dihydroartemisinin (n=14 monotherapy tablets, not recommended by WHO, were also identified.Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained.

  18. Study on the treatment of children dependent on network game of psychological intervention combined with drug%心理干预联合药物对网络游戏依赖儿童的疗效

    Institute of Scientific and Technical Information of China (English)

    王东平; 卫世强; 詹合琴

    2014-01-01

    Objective To study the curative effect of psychological intervention combined with drug treatment of children addicted to the network game.Methods One hundred and twelve children addicted to the network game were selected,who were admitted to the outpatient department of the Second Affiliated Hospital of Xinxiang Medical University from Feb.2009 to Oct.2013 were selected,according to the admission time sequence,they were randomly divided into drug treatment group,psychological intervention group(as control group) and psychological intervention combined with drug therapy group(test group).Each of the control groups had 38 cases of patients,while treatment group had 36 cases.Drug treatment group was treated with oral Fluoxetine Hydrochloride Capsules 10 mg,1 time/d; the psychological intervention group was given the general psychological conversation,until discharged from the hospital; the test group adopted the cognitive restructuring,imagine the debate,self suggestion,remind yourself of cognitive therapy and behavior contract,behavior reinforcement,behavior extinction,aversive stimulus,self-regulation of behavior therapy combined with drug therapy.Respectively,before treatment,2 weeks,4 weeks and 8 weeks after the end of the treatment,Chinese Internet Addiction Scale,Coping Style Questionnaire (CSQ) and symptom checklist 90 (SCL-90) of each factor were evaluated.Results By the end of the 2 weeks and 8 weeks after the treatment,CIAS scores in the treatment group were significantly lower than that in drug therapy and psychological intervention group,the differences were statistically significant (t =2.49,2.03,all P < 0.05 ; t =2.72,2.72,all P < 0.01) ; scores of 3 factors of fantasy,self accusation and retreat in CSQ group in coping style questiennaire in the coping style questionnaire in the treatment group were lower than those in control groups,the differences were statistically significant (t =3.99,3.78,2.15,all P < 0.05; t=2.64,4.20,3.72,all P < 0

  19. Curative Effect Observation of Anti VEGF Drugs Combined Laser Photocoagulation in Treatment of Diabetic Macular Edema%抗VEGF药物联合激光光凝治疗糖尿病黄斑水肿的疗效观察

    Institute of Scientific and Technical Information of China (English)

    张凤; 王琇; 公慧敏

    2015-01-01

    目的:分析和研究抗 VEGF 药物联合激光光凝治疗糖尿病黄斑水肿的疗效。方法选取2012年8月~2014年9月糖尿病黄斑水肿患者44例,分为抗 VEGF +光凝组与光凝组,光凝组患者给予激光光凝;抗 VEGF +光凝组患者给予抗 VEGF 药物联合激光光凝治疗,对比治疗前和治疗6个月两组最佳矫正视力(BCVA)、黄斑中心凹厚度(CMT)、安全性和注射次数。结果治疗前,两组患者两组 BCVA 水平、CMT 水平经 t 检验显示差异无统计学意义(P >0.05)。治疗6个月两组 BCVA 水平均提高、CMT 水平均降低,经 t 检验显示差异有统计学意义(P <0.05),但抗 VEGF +光凝组 BCVA 水平、CMT 水平改善幅度优于光凝组,经t 检验显示差异有统计学意义(P <0.05)。经随访,光凝组和抗 VEGF +光凝组均未出现视网膜脱落、眼内炎、晶状体损伤、眼压升高、玻璃体积血、色素上皮撕裂、地图状萎缩等眼部不良反应或中风、心脏病等全身不良反应,组间经χ2检验显示差异无统计学意义(P >0.05)。结论抗 VEGF 药物联合激光光凝治疗糖尿病黄斑水肿的疗效确切,可改善患者视力和视网膜厚度。%Objective To analyze and research of VEGF drugs combined laser photocoagulation for treatment of diabetic macular edema. Methods Selected 44 patients with diabetic macular edema in August 2012 to September 2014,divided into anti VEGF+photocoagulation and photocoagulation group. Photocoagulation group patients given laser photocoagulation. Anti VEGF + photocoagulation group patients given fight VEGF drugs combined laser photocoagulation for treatment,compared before and 6 months after treatment in the two groups best corrected visual acuity(BCVA)and macular center concave thickness(CMT),security,and injection time. Results Before the treatment,two groups of patients,the CMT the BCVA level two groups of t test showed that

  20. The effect of drugs combined with psychological intervention on children with attention deficit hyperactivity disorder%药物联合心理干预治疗儿童多动症患者疗效观察

    Institute of Scientific and Technical Information of China (English)

    常宪鲁; 王华云

    2012-01-01

    Objective: To explore effect of psychological intervention combined with drugs on children with attention-deficit/hyperactivity disorder. Method:56 children with attention-deficit/hyperactivity disorder were divided into intervention group ( n = 28) and control group ( n = 28 ) . The intervention group received both methylphenidate treatment and psychological intervention which included behavioral, family supportive and bio-feedback therapy,while the control group received methylphenidate therapy only. All patients were evaluated with ConnerS parent rating scale before and after 6-week treatment. Results: The symptom of two groups im proved significantly after 6-week treatment (P <0. 01) ,but conduct,hyperactivity and hyperactivity index im proved more in the intervention group than in the control group ( P < 0. 01). Conclusion: Psychological inter vention plus drug treatment may improve symptoms more than single drug treatment in the treatment of children with attention-deficit/hyperactivity.%目的:探讨药物联合心理干预对儿童多动症患者的疗效.方法:56例多动症患儿随机分为干预组(28例)和对照组(28例),对干预组予哌甲酯治疗外,实施6周心理干预(行为干预、家庭支持治疗及生物反馈);对照组仅予哌甲酯治疗.两组均于治疗开始及治疗6周实施Corners父母问卷测验.结果:治疗6周后,两组症状较治疗前均有改善,差异有统计学意义(P<0.01).干预组较对照组品行问题、冲动多动问题、多动指数因子分进步更为明显(P<0.01).结论:心理干预联合药物治疗比单独药物治疗可更好地改善多动症患儿的症状.

  1. New antiretrovirals and new combinations.

    Science.gov (United States)

    Havlir, D V; Lange, J M

    1998-01-01

    The appearance in the clinic of two to three new antiretroviral agents yearly since 1995 has permitted unprecedented advances in HIV treatment. This remarkable pace of drug development is a testimony to an extraordinary international effort involving scientists, clinicians, governments, community activists and industry dedicated to the rapid and safe development of novel therapies. New drugs present the opportunity to improve HIV therapy. They also create an enormous challenge to the clinician, who must constantly assimilate data on new drugs and incorporate this information into practical management strategies. Combination therapy has proven the most effective approach to treat HIV disease. The profound and sustained viral suppression achievable with combinations such as indinavir (IDV), lamivudine (3TC) and zidovudine (ZDV) have resulted in a dramatic shift in HIV treatment paradigms over the last year. The full potential of combination therapy with available drugs has yet to be realized as only a limited number of the possible combinations incorporating new drugs have been fully tested. Even drugs available for many years may have untapped potential. Didanosine (ddI) and stavudine (d4T), once thought to be contraindicated in combination because of their overlapping peripheral neuropathy toxicity, have proven well tolerated and effective. Combination therapy can increase antiviral suppression, prevent drug resistance, optimize drug exposure and simplify dosing, but it can also result in pharmacologic antagonism, subtherapeutic drug concentrations and unexpected toxicities. Clinical studies have confirmed in vitro studies showing pharmacologic antagonism for the combination of ZDV and d4T. Combining protease inhibitors with each other or with non-nucleoside reverse transcriptase inhibitors is complicated by effects both classes of drugs have on drug metabolism and clearance. These observations underline the importance of carefully conducted clinical studies to

  2. Drug Facts

    Medline Plus

    Full Text Available ... form Search Menu Home Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) ... addiction and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other ...

  3. Drug Facts

    Medline Plus

    Full Text Available ... People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, ... and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Bodies Drug Abuse Hurts Brains Drug Abuse and Mental Health Problems Often Happen Together The Link Between ... This Website Tools and Resources | Contact Us | Site Map | Accessibility | Privacy | FOIA (NIH) The National Institute on ...

  5. Drug Facts

    Medline Plus

    Full Text Available Easy-to-Read Drug Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) ... and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs ...

  7. Drug Facts

    Medline Plus

    Full Text Available ... abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco ... 662-HELP (4357) at any time to find drug treatment centers near you. I want my daughter ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... Search form Search Menu Home Drugs That People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, ... Pain Medicine (Oxy, Vike) Facts Other Drugs of Abuse What is Addiction? Do You or a Loved ...

  9. Drug Facts

    Medline Plus

    Full Text Available ... Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts Meth ( ... treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... People Abuse Alcohol Facts Cigarette and Tobacco Facts Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana ( ... and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Cocaine (Coke, Crack) Facts Heroin (Smack, Junk) Facts Marijuana (Weed, Pot) Facts Meth (Crank, Ice) Facts Pain ... Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Numbers and Websites Search Share Listen English Español Information about this page Click on the button that ... about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain ...

  13. 桂枝汤药物规律性组合及其类方系统结合病机理论探讨“证”内涵(二)%Regularity Drugs Combination of Cinnamon Twig Decoction and Study on Connotation of Syndrome Based on Its Class Decoction System Combined with the Theory of Pathogenesis (Two)

    Institute of Scientific and Technical Information of China (English)

    郭文娟; 烟建华

    2012-01-01

    用文献和数据挖掘的[方法]和方药——病机——证的逆向思维,从桂枝汤的药物规律性组合及其类方系统与证机相关性来探讨“证”的内涵.得出“证”内涵具有如下特性:功能关系性、整体关联性、动态时空性、模型性、多维意象性.%By the methods of literature and data mining and the reverse thinking of herbs - pathogenesis - syndrome, study on the connotation of syndrome from regularity drugs combination of cinnamon twig decoction was made from its class decoction system combined with the theory of pathogenesis. We obtained the following characteristics of the connotation of syndrome:function relation, integrated relation,dynamic 3pace-time relation,modularity and multi -dimensional image.

  14. Study on Connotation of Syndrome by Combination of Regularity Drugs Combination of Cinnamon Twig Decoction and Its Class Decoction System and Theory of Pathogenesis(One)%桂枝汤药物规律性组合及其类方系统结合病机理论探讨“证”内涵(一)

    Institute of Scientific and Technical Information of China (English)

    郭文娟; 烟建华

    2012-01-01

    用文献和数据挖掘的方法和方药——病机——证的逆向思维,从桂枝汤的药物规律性组合及其类方系统与其证机相关性来探讨“证”内涵.得出“证”内涵具有如下特性:功能关系性、整体关联性、动态时空性、模型性、多维意象性.%Study on the connotation of syndrome from regularity drugs combination of cinnamon twig decoction and its class decoction system combined with the theory of pathogenesis was made with the methods of literature and data mining and the reverse thinking of herbs - pathogenesis - syndrome. We obtained the following characteristics of the connotation of syndrome:function,overall and relative relation, dynamics of space - time,model and multi - dimensional image.

  15. Drug Addiction

    OpenAIRE

    Justinova, Zuzana; Panlilio, Leigh V; Goldberg, Steven R.

    2009-01-01

    Many drugs of abuse, including cannabinoids, opioids, alcohol and nicotine, can alter the levels of endocannabinoids in the brain. Recent studies show that release of endocannabinoids in the ventral tegmental area can modulate the reward-related effects of dopamine and might therefore be an important neurobiological mechanism underlying drug addiction. There is strong evidence that the endocannabinoid system is involved in drug-seeking behavior (especially behavior that is reinforced by drug-...

  16. Medicaid Drugs

    OpenAIRE

    Poisal, John A.

    2004-01-01

    The following commentary unites a collection of articles primarily concerned with prescription drug issues in Medicaid. It also features highlights from a piece outlining Australia's pharmaceutical delivery system. Specifically, in this issue, you will find comprehensive analyses of drug expenditure trends, issues regarding access to pharmaceuticals in Medicaid, and an evaluation of ongoing generic drug cost-containment programs.

  17. Drug Facts

    Medline Plus

    Full Text Available ... you. This web site talks about drug abuse, addiction and treatment. Watch Videos Information About Drugs Alcohol Cocaine Heroin ... HELP (4357) at any time to find drug treatment centers near you. ... addiction. Counseling is very helpful to her. All I ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Watch Videos Information About Drugs Alcohol Cocaine Heroin Marijuana Meth Pain Medicines Tobacco Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment centers near ... different people around me. To stop using marijuana, "Cristina" is making positive changes in her life. ...

  19. Inhibition of Single Drug and Combined Drugs in Qizhu Decoction to the Proliferation of Human Gastric Cancer Cell MGC -803%芪竹方中单体及配伍对人胃癌细胞MGC-803抑制作用研究

    Institute of Scientific and Technical Information of China (English)

    王卯; 叶丽红

    2012-01-01

    目的:观察芪竹方单体成分薯蓣皂苷、莪术醇及两者配伍对人胃癌细胞MGC - 803的增殖抑制作用,初步探讨芪竹方复方在抗肿瘤治疗中的有效成分及作用机制.方法:选用5个剂量的薯蓣皂苷、莪术醇单药组,及2个剂量的两药配伍组在24h、48h 2个不同时间点作用人胃癌细胞MGC - 803,采用MTT法检测药物对MGC - 803的增殖抑制率.结果:一定浓度范围内,薯蓣皂苷及莪术醇均对MGC -803细胞的增殖有剂量、时间依赖性抑制作用,且两药配伍使用较单药能产生更好的抑制作用.结论:薯蓣皂苷及莪术醇可能为芪竹方抑制人胃癌细胞MGC - 803增殖的有效成分.%Objective;To observe the inhibition of curcumol and dioscin and their combination from Qizhu decoction to the proliferation of human gastric cancer cell MGC - 803, and to investigate the active principles and anti - tumor mechanisms of Qizhu decoction. Methods; MGC - 803 was treated with five dosages of curcumol and dioscin single and two dosages of the combination of curcumol and dioscin for two times at the points of 24h and 48h, and the inhibitory rate of the drugs on MGC - 803 proliferation was detected by MTT assay. Results: Within a certain concentration range, both curcumol dioscin have the time - and - dose - dependent inhibitional effect on the proliferation of MGC - 803, and using the combination of curcumol and dioscin has a better effect than using single of the two drugs. Conclusions; Curcumol and dioscin from the Qizhu decoction might be the active principles in inhibiting the proliferation of MGC -803.

  20. Drug allergy

    Directory of Open Access Journals (Sweden)

    Warrington Richard

    2011-11-01

    Full Text Available Abstract Drug allergy encompasses a spectrum of immunologically-mediated hypersensitivity reactions with varying mechanisms and clinical presentations. This type of adverse drug reaction (ADR not only affects patient quality of life, but may also lead to delayed treatment, unnecessary investigations, and even mortality. Given the myriad of symptoms associated with the condition, diagnosis is often challenging. Therefore, referral to an allergist experienced in the identification, diagnosis and management of drug allergy is recommended if a drug-induced allergic reaction is suspected. Diagnosis relies on a careful history and physical examination. In some instances, skin testing, graded challenges and induction of drug tolerance procedures may be required. The most effective strategy for the management of drug allergy is avoidance or discontinuation of the offending drug. When available, alternative medications with unrelated chemical structures should be substituted. Cross-reactivity among drugs should be taken into consideration when choosing alternative agents. Additional therapy for drug hypersensitivity reactions is largely supportive and may include topical corticosteroids, oral antihistamines and, in severe cases, systemic corticosteroids. In the event of anaphylaxis, the treatment of choice is injectable epinephrine. If a particular drug to which the patient is allergic is indicated and there is no suitable alternative, induction of drug tolerance procedures may be considered to induce temporary tolerance to the drug. This article provides a backgrounder on drug allergy and strategies for the diagnosis and management of some of the most common drug-induced allergic reactions, such allergies to penicillin, sulfonamides, cephalosporins, radiocontrast media, local anesthetics, general anesthetics, acetylsalicylic acid (ASA and non-steroidal anti-inflammatory drugs.