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Sample records for chemotherapeutic treatment efficacy

  1. Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields)

    PubMed Central

    Kirson, Eilon D; Schneiderman, Rosa S; Dbalý, Vladimír; Tovaryš, František; Vymazal, Josef; Itzhaki, Aviran; Mordechovich, Daniel; Gurvich, Zoya; Shmueli, Esther; Goldsher, Dorit; Wasserman, Yoram; Palti, Yoram

    2009-01-01

    Background The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. Methods Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients. Results The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months. Conclusion These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity. PMID:19133110

  2. Chemotherapeutic Agents for the Treatment of Hepatocellular Carcinoma: Efficacy and Mode of Action

    PubMed Central

    Shaaban, Saad; Negm, Amr; Ibrahim, Elsayed E.; Elrazak, Ahmed A.

    2014-01-01

    Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be also described for each drug. PMID:25992234

  3. Vascular Priming Enhances Chemotherapeutic Efficacy against Head and Neck Cancer

    PubMed Central

    Folaron, Margaret; Kalmuk, James; Lockwood, Jaimee; Frangou, Costakis; Vokes, Jordan; Turowski, Steven G.; Merzianu, Mihai; Rigual, Nestor R.; Sullivan-Nasca, Maureen; Kuriakose, Moni A.; Hicks, Wesley L.; Singh, Anurag K.; Seshadri, Mukund

    2013-01-01

    Purpose The need to improve chemotherapeutic efficacy against head and neck squamous cell carcinomas (HNSCC) is well recognized. In this study, we investigated the potential of targeting the established tumor vasculature in combination with chemotherapy in head and neck cancer. Methods Experimental studies were carried out in multiple human HNSCC xenograft models to examine the activity of the vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in combination with chemotherapy. Multimodality imaging (magnetic resonance imaging, bioluminescence) in conjunction with drug delivery assessment (fluorescence microscopy), histopathology and microarray analysis was performed to characterize tumor response to therapy. Long-term treatment outcome was assessed using clinically-relevant end points of efficacy. Results Pretreatment of tumors with VDA prior to administration of chemotherapy increased intratumoral drug delivery and treatment efficacy. Enhancement of therapeutic efficacy was dependent on the dose and duration of VDA treatment but was independent of the chemotherapeutic agent evaluated. Combination treatment resulted in increased tumor cell kill and improvement in progression-free survival and overall survival in both ectopic and orthotopic HNSCC models. Conclusion Our results show that preconditioning of the tumor microenvironment with an antivascular agent primes the tumor vasculature and results in enhancement of chemotherapeutic delivery and efficacy in vivo. Further investigation into the activity of antivascular agents in combination with chemotherapy against HNSCC is warranted. PMID:23890930

  4. The Use of Chemotherapeutics for the Treatment of Keloid Scars

    PubMed Central

    Jones, Christopher David; Guiot, Luke; Samy, Mike; Gorman, Mark; Tehrani, Hamid

    2015-01-01

    Keloid scars are pathological scars, which develop as a result of exaggerated dermal tissue proliferation following cutaneous injury and often cause physical, psychological and cosmetic problems. Various theories regarding keloidogenesis exist, however the precise pathophysiological events remain unclear. Many different treatment modalities have been implicated in their management, but currently there is no entirely satisfactory method for treating all keloid lesions. We review a number of different chemotherapeutic agents which have been proposed for the treatment of keloid and hypertrophic scars while giving insight into some of the novel chemotherapeutic drugs which are currently being investigated. Non-randomized trials evaluating the influence of different chemotherapeutic agents, such as 5-fluorouracil (5-FU); mitomycin C; bleomycin and steroid injection, either alone or in combination with other chemotherapeutic agents or alternative treatment modalities, for the treatment of keloids were identified using a predefined PubMed search strategy. Twenty seven papers were identified. Scar improvement ≥50% was found in the majority of cases treated with 5-FU, with similar results found for mitomycin C, bleomycin and steroid injection. Combined intralesional 5-FU and steroid injection produced statistically significant improvements when compared to monotherapy. Monotherapy recurrence rates ranged from 0-47% for 5-FU, 0-15% for bleomycin and 0-50% for steroid injection. However, combined therapy in the form of surgical excision and adjuvant 5-FU or steroid injections demonstrated lower recurrence rates; 19% and 6% respectively. Currently, most of the literature supports the use of combination therapy (usually surgery and adjuvant chemotherapy) as the mainstay treatment of keloids, however further investigation is necessary to determine success rates over longer time frames. Furthermore, there is the potential for novel therapies, but further investigation is

  5. Efficacy of combined photothermal therapy and chemotherapeutic drugs

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Shih, En-Chung; Hirschberg, Henry

    2015-03-01

    Hyperthermia has been shown to enhance the effects of chemotherapeutic agents in a wide variety of cancers. The purpose of this study was to investigate the combined effects of a number of commonly used chemotherapeutic drugs (bleomycin, doxorubicin and cisplatin) with photothermal therapy (PTT)-induced hyperthermia in an in vitro system consisting of human head and neck squamous carcinoma cells and murine lymphocytic monocytes which were used as delivery vehicles for gold-silica nanoshells (AuNS). PTT was accomplished via near infra-red (NIR) irradiation of AuNS. The results showed that PTT combined with cisplatin resulted in only a mild degree of synergism while additive effects were observed for concurrent treatments of PTT and doxorubicin and PTT and bleomycin.

  6. Synthetic lethal approaches for assessing combinatorial efficacy of chemotherapeutic drugs.

    PubMed

    Jackson, Rebecca A; Chen, Ee Sin

    2016-06-01

    The recent advances in pharmacogenomics have made personalized medicine no longer a pipedream but a precise and powerful way to tailor individualized cancer treatment strategies. Cancer is a devastating disease, and contemporary chemotherapeutic strategies now integrate several agents in the treatment of some types of cancer, with the intent to block more than one target simultaneously. This constitutes the premise of synthetic lethality, an attractive therapeutic strategy already demonstrating clinical success in patients with breast and ovarian cancers. Synthetic lethal combinations offer the potential to also target the hitherto "undruggable" mutations that have challenged the cancer field for decades. However, synthetic lethality in clinical cancer therapy is very much still in its infancy, and selecting the most appropriate combinations-or synthetic lethal pairs-is not always an intuitive process. Here, we review some of the recent progress in identifying synthetic lethal combinations and their potential for therapy and highlight some of the tools through which synthetic lethal pairs are identified.

  7. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment.

    PubMed

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-05-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  8. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment

    PubMed Central

    Kang, Lin; Gao, Zhonggao; Huang, Wei; Jin, Mingji; Wang, Qiming

    2015-01-01

    The efficacy of chemotherapeutic drug in cancer treatment is often hampered by drug resistance of tumor cells, which is usually caused by abnormal gene expression. RNA interference mediated by siRNA and miRNA can selectively knock down the carcinogenic genes by targeting specific mRNAs. Therefore, combining chemotherapeutic drugs with gene agents could be a promising strategy for cancer therapy. Due to poor stability and solubility associated with gene agents and drugs, suitable protective carriers are needed and have been widely researched for the co-delivery. In this review, we summarize the most commonly used nanocarriers for co-delivery of chemotherapeutic drugs and gene agents, as well as the advances in co-delivery systems. PMID:26579443

  9. Improvement of chemotherapeutic drug efficacy by endoplasmic reticulum stress.

    PubMed

    Mihailidou, Chrysovalantou; Chatzistamou, Ioulia; Papavassiliou, Athanasios G; Kiaris, Hippokratis

    2015-04-01

    Tunicamycin (TUN), an inhibitor of protein glycosylation and therefore a potent stimulator of endoplasmic reticulum (ER) stress, has been used to improve anticancer drug efficacy, but the underlying mechanism remains obscure. In this study, we show that acute administration of TUN in mice induces the unfolded protein response and suppresses the levels of P21, a cell cycle regulator with anti-apoptotic activity. The inhibition of P21 after ER stress appears to be C/EBP homologous protein (CHOP)-dependent because in CHOP-deficient mice, TUN not only failed to suppress, but rather induced the expression of P21. Results of promoter-activity reporter assays using human cancer cells and mouse fibroblasts indicated that the regulation of P21 by CHOP operates at the level of transcription and involves direct binding of CHOP transcription factor to the P21 promoter. The results of cell viability and clonogenic assays indicate that ER-stress-related suppression of P21 expression potentiates caspase activation and sensitizes cells to doxorubicin treatment, while administration of TUN to mice increases the therapeutic efficacy of anticancer therapy for HepG2 liver and A549 lung cancers.

  10. Role of pregnane X receptor in chemotherapeutic treatment

    PubMed Central

    Zhuo, Wei; Hu, Lei; Lv, Jinfeng; Wang, Hongbing; Zhou, Honghao; Fan, Lan

    2015-01-01

    Pregnane X receptor (PXR) is a member of the nuclear receptor superfamily that differently expresses not only in human normal tissues but also in numerous types of human cancers. PXR can be activated by many endogenous substances and exogenous chemicals, and thus affects chemotherapeutic effects and intervenes drug–drug interactions by regulating its target genes involving drug metabolism and transportation, cell proliferation and apoptosis, and modulating endobiotic homeostasis. Tissue and context-specific regulation of PXR contributes to diverse effects in the treatment for numerous cancers. Genetic variants of PXR lead to intra- and inter-individual differences in the expression and inducibility of PXR, resulting in different responses to chemotherapy in PXR-positive cancers. The purpose of this review is to summarize and discuss the role of PXR in the metabolism and clearance of anticancer drugs. It is also expected that this review will provide insights into PXR-mediated enhancement for chemotherapeutic treatment, prediction of drug–drug interactions and personalized medicine. PMID:24889719

  11. Engineering novel targeted nanoparticle formulations to increase the therapeutic efficacy of conventional chemotherapeutics against multiple myeloma

    NASA Astrophysics Data System (ADS)

    Ashley, Jonathan D.

    Multiple myeloma (MM) is a hematological malignancy which results from the uncontrolled clonal expansion of plasma cells within the body. Despite recent medical advances, this disease remains largely incurable, with a median survival of ˜7 years, owing to the development of drug resistance. This dissertation will explore new advances in nanotechnology that will combine the cytotoxic effects of small molecule chemotherapeutics with the tumor targeting capabilities of nanoparticles to create novel nanoparticle formulations that exhibit enhanced therapeutic indices in the treatment of MM. First, doxorubicin was surfaced conjugated onto micellar nanoparticles via an acid labile hydrazone bond to increase the drug accumulation at the tumor. The cell surface receptor Very Late Antigen-4 (VLA-4; alpha4beta1) is expressed on cancers of hematopoietic origin and plays a vital role in the cell adhesion mediated drug resistance (CAM-DR) in MM. Therefore, VLA-4 antagonist peptides were conjugated onto the nanoparticles via a multifaceted procedure to actively target MM cells and simultaneously inhibit CAM-DR. The micellar doxorubicin nanoparticles were able to overcome CAM-DR and demonstrated improved therapeutic index relative to free doxorubicin. In addition to doxorubicin, other classes of therapeutic agents, such as proteasome inhibitors, can be incorporated in nanoparticles for improved therapeutic outcomes. Utilizing boronic acid chemistry, bortezomib prodrugs were synthesized using a reversible boronic ester bond and then incorporated into liposomes. The different boronic ester bonds that could be potentially used in the synthesis of bortezomib prodrugs were screened based on stability using isobutylboronic acid. The liposomal bortezomib nanoparticles demonstrated significant proteasome inhibition and cytotoxicity in MM cells in vitro, and dramatically reduced the non-specific toxicities associated with free bortezomib while maintaining significant tumor growth

  12. Nobiletin enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cancer cells.

    PubMed

    Ma, Wenzhe; Feng, Senling; Yao, Xiaojun; Yuan, Zhongwen; Liu, Liang; Xie, Ying

    2015-12-22

    Multidrug resistance (MDR) is the major obstacle to the successful chemotherapy treatment of many cancers. Here we found that nobiletin, a citrus methoxyflavone, significantly sensitized ABCB1 overexpressing cells A2780/T and A549/T to chemotherapeutic agents such as paclitaxel (a 433-fold reversal of MDR to PTX at 9 μM), doxorubicin (DOX), docetaxel and dounorubicin. Nobiletin profoundly inhibited ABCB1 transporter activity since it significantly increased the intracellular accumulation of DOX and Flutax-2 in A2780/T cells and decreased the efflux of ABCB1 substrates in Caco2 cells without altering the mRNA and protein expression of ABCB1. Moreover, nobiletin stimulated ATPase activity and inhibited verapamil-stimulated ATPase activity in a concentration-dependent manner, indicating a direct interaction with the transporter. Consistent with these findings, molecular docking analysis also identified favorable binding of nobiletin with the transmemberane region site 1 of homology modeled human ABCB1 transporter. Moreover, the Nrf2 protein expression and phosphorylation levels of AKT/ERK were suppressed by co-treated with nobiletin and PTX at the reversal concentrations, suggesting that inhibition of the AKT/ERK/Nrf2 pathway was associated with the sensitizing effect of nobiletin. These findings encourage further animal and clinical MDR studies with the combination therapy of nobiletin and chemotherapeutic drugs.

  13. Nobiletin enhances the efficacy of chemotherapeutic agents in ABCB1 overexpression cancer cells

    PubMed Central

    Ma, Wenzhe; Feng, Senling; Yao, Xiaojun; Yuan, Zhongwen; Liu, Liang; Xie, Ying

    2015-01-01

    Multidrug resistance (MDR) is the major obstacle to the successful chemotherapy treatment of many cancers. Here we found that nobiletin, a citrus methoxyflavone, significantly sensitized ABCB1 overexpressing cells A2780/T and A549/T to chemotherapeutic agents such as paclitaxel (a 433-fold reversal of MDR to PTX at 9 μM), doxorubicin (DOX), docetaxel and dounorubicin. Nobiletin profoundly inhibited ABCB1 transporter activity since it significantly increased the intracellular accumulation of DOX and Flutax-2 in A2780/T cells and decreased the efflux of ABCB1 substrates in Caco2 cells without altering the mRNA and protein expression of ABCB1. Moreover, nobiletin stimulated ATPase activity and inhibited verapamil-stimulated ATPase activity in a concentration-dependent manner, indicating a direct interaction with the transporter. Consistent with these findings, molecular docking analysis also identified favorable binding of nobiletin with the transmemberane region site 1 of homology modeled human ABCB1 transporter. Moreover, the Nrf2 protein expression and phosphorylation levels of AKT/ERK were suppressed by co-treated with nobiletin and PTX at the reversal concentrations, suggesting that inhibition of the AKT/ERK/Nrf2 pathway was associated with the sensitizing effect of nobiletin. These findings encourage further animal and clinical MDR studies with the combination therapy of nobiletin and chemotherapeutic drugs. PMID:26689156

  14. A Novel Agent Enhances the Chemotherapeutic Efficacy of Doxorubicin in MCF-7 Breast Cancer Cells

    PubMed Central

    Wang, Liang; Chan, Judy Y.; Zhou, Xinhua; Cui, Guozhen; Yan, Zhixiang; Wang, Li; Yan, Ru; Di, Lijun; Wang, Yuqiang; Hoi, Maggie P.; Shan, Luchen; Lee, Simon M.

    2016-01-01

    We have previously demonstrated that DT-010, a novel conjugate of danshensu (DSS) and tetramethylpyrazine (TMP), displays anti-tumor effects in breast cancer cells both in vitro and in vivo. In the present study, we investigated whether DT-010 enhances the chemotherapeutic effect of doxorubicin (Dox) in MCF-7 breast cancer cells and exerts concurrent cardioprotective benefit at the same time. Our findings showed that DT-010 was more potent than TMP, DSS, or their combination in potentiating Dox-induced toxicity in MCF-7 cells. Co-treatment with DT-010 and Dox increased apoptosis in MCF-7 cells relative to Dox alone. Further study indicated that glycolytic capacity, glycolytic reserve and lactate level of MCF-7 cells were significantly inhibited after DT-010 treatment. DT-010 also increased the expression of the pro-survival protein GRP78, which was inhibited by co-treatment with Dox. Both endoplasmic reticulum stress inhibitor 4-PBA and knockdown of the expression of GRP78 protein potentiated DT-010-mediated apoptosis in MCF-7 cells. Moreover, DT-010 inhibited Dox-induced cardiotoxicity in H9c2 myoblasts. In conclusion, DT-010 and Dox confer synergistic anti-tumor effect in MCF-7 breast cancer cells through downregulation of the glycolytic pathway and inhibition of the expression of GRP78. Meanwhile, DT-010 also protects against Dox-induced cardiotoxicity. PMID:27559313

  15. [Nutrition, lifestyle, physical activity, and supportive care during chemotherapeutic treatment].

    PubMed

    Lümmen, G; Jäger, T; Sommer, F; Ebert, T; Schmitz-Draeger, B

    2006-05-01

    With improvements in cancer survival rates, more patients with cancer are living longer and the influence of nutrition, lifestyle, physical activity as well as supportive care during and after chemotherapy is of increasing interest. In several malignancies smoking cessation increases cancer survival. Similar effects are expected by healthy nutrition. Regular physical activity of cancer patients reduces drug interactions of chemotherapy, decreases the number of comorbid conditions, and helps patients maintain independence as long as possible. For supportive care during chemotherapy the 5-HT3 receptor antagonists are more effective for the prevention of chemotherapy-induced nausea and vomiting. There are several colony-stimulating factors (e.g. GCSF, erythropoietin) for hematopoietic recovery post-chemotherapy. Altogether supportive care of chemotherapy reduces toxicity and increases efficacy.

  16. Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics

    PubMed Central

    2016-01-01

    Conventional chemotherapeutics remain essential treatments for most cancers, but their combination with other anticancer drugs (including targeted therapeutics) is often complicated by unpredictable synergies and multiplicative toxicities. As cytotoxic anticancer chemotherapeutics generally function through induction of apoptosis, we hypothesized that a molecularly targeted small molecule capable of facilitating a central and defining step in the apoptotic cascade, the activation of procaspase-3 to caspase-3, would broadly and predictably enhance activity of cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1) enhances cancer cell death induced by 15 different FDA-approved chemotherapeutics, across many cancer types and chemotherapeutic targets. In particular, the promising combination of PAC-1 and doxorubicin induces a synergistic reduction in tumor burden and enhances survival in murine tumor models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of 4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC-1 with doxorubicin resulted in no additional toxicity. On the basis of the mode of action of PAC-1 and the high expression of procaspase-3 in many cancers, these results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a potent and general strategy to enhance therapeutic response.

  17. Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics

    PubMed Central

    2016-01-01

    Conventional chemotherapeutics remain essential treatments for most cancers, but their combination with other anticancer drugs (including targeted therapeutics) is often complicated by unpredictable synergies and multiplicative toxicities. As cytotoxic anticancer chemotherapeutics generally function through induction of apoptosis, we hypothesized that a molecularly targeted small molecule capable of facilitating a central and defining step in the apoptotic cascade, the activation of procaspase-3 to caspase-3, would broadly and predictably enhance activity of cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1) enhances cancer cell death induced by 15 different FDA-approved chemotherapeutics, across many cancer types and chemotherapeutic targets. In particular, the promising combination of PAC-1 and doxorubicin induces a synergistic reduction in tumor burden and enhances survival in murine tumor models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of 4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC-1 with doxorubicin resulted in no additional toxicity. On the basis of the mode of action of PAC-1 and the high expression of procaspase-3 in many cancers, these results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a potent and general strategy to enhance therapeutic response. PMID:27610416

  18. Small-Molecule Procaspase-3 Activation Sensitizes Cancer to Treatment with Diverse Chemotherapeutics.

    PubMed

    Botham, Rachel C; Roth, Howard S; Book, Alison P; Roady, Patrick J; Fan, Timothy M; Hergenrother, Paul J

    2016-08-24

    Conventional chemotherapeutics remain essential treatments for most cancers, but their combination with other anticancer drugs (including targeted therapeutics) is often complicated by unpredictable synergies and multiplicative toxicities. As cytotoxic anticancer chemotherapeutics generally function through induction of apoptosis, we hypothesized that a molecularly targeted small molecule capable of facilitating a central and defining step in the apoptotic cascade, the activation of procaspase-3 to caspase-3, would broadly and predictably enhance activity of cytotoxic drugs. Here we show that procaspase-activating compound 1 (PAC-1) enhances cancer cell death induced by 15 different FDA-approved chemotherapeutics, across many cancer types and chemotherapeutic targets. In particular, the promising combination of PAC-1 and doxorubicin induces a synergistic reduction in tumor burden and enhances survival in murine tumor models of osteosarcoma and lymphoma. This PAC-1/doxorubicin combination was evaluated in 10 pet dogs with naturally occurring metastatic osteosarcoma or lymphoma, eliciting a biologic response in 3 of 6 osteosarcoma patients and 4 of 4 lymphoma patients. Importantly, in both mice and dogs, coadministration of PAC-1 with doxorubicin resulted in no additional toxicity. On the basis of the mode of action of PAC-1 and the high expression of procaspase-3 in many cancers, these results suggest the combination of PAC-1 with cytotoxic anticancer drugs as a potent and general strategy to enhance therapeutic response. PMID:27610416

  19. Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001.

    PubMed

    Uneke, C J

    2010-01-01

    Soil transmitted helminth infections (STH) and schistosomiasis constitute major public health challenges among school-age children in sub-Saharan Africa. This review assessed the efficacy of chemotherapeutic intervention in line with the World Health Assembly (WHA) resolution since the passage in 2001. Using the Medline Entrez-Pubmed search, relevant publications were identified via combinations of key words such as helminth infection, school children, chemotherapy, Africa. Albendazole, mebendazole, and praziquantel were the antihelminthic drugs most commonly evaluated. Cure rates >80% and egg reduction rates >90% were recorded in most cases of schistosomiasis using praziquantel. Albendazole was very effective against A. lumbricoides and hookworm infections with majority of the studies recording cure rates >75%, but the efficacy of the drug was poor against T. trichiura. To ensure the realization of the WHA resolution, there is need for regular treatment of school children, development of alternative antihelminthic drugs and vaccines, environmental control measures and health education.

  20. Soil transmitted helminth infections and schistosomiasis in school age children in sub-Saharan Africa: efficacy of chemotherapeutic intervention since World Health Assembly Resolution 2001.

    PubMed

    Uneke, C J

    2010-01-01

    Soil transmitted helminth infections (STH) and schistosomiasis constitute major public health challenges among school-age children in sub-Saharan Africa. This review assessed the efficacy of chemotherapeutic intervention in line with the World Health Assembly (WHA) resolution since the passage in 2001. Using the Medline Entrez-Pubmed search, relevant publications were identified via combinations of key words such as helminth infection, school children, chemotherapy, Africa. Albendazole, mebendazole, and praziquantel were the antihelminthic drugs most commonly evaluated. Cure rates >80% and egg reduction rates >90% were recorded in most cases of schistosomiasis using praziquantel. Albendazole was very effective against A. lumbricoides and hookworm infections with majority of the studies recording cure rates >75%, but the efficacy of the drug was poor against T. trichiura. To ensure the realization of the WHA resolution, there is need for regular treatment of school children, development of alternative antihelminthic drugs and vaccines, environmental control measures and health education. PMID:20737834

  1. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction.

    PubMed

    Das, Anindita; Durrant, David; Mitchell, Clint; Mayton, Eric; Hoke, Nicholas N; Salloum, Fadi N; Park, Margaret A; Qureshi, Ian; Lee, Ray; Dent, Paul; Kukreja, Rakesh C

    2010-10-19

    We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induced apoptosis in PC-3 and DU145 prostate cancer cells, which was mediated by enhanced generation of reactive oxygen species, up-regulation of caspase-3 and caspase-9 activities, reduced expression of Bcl-xL, and phosphorylation of Bad. Overexpression of Bcl-xL or dominant negative caspase 9 attenuated the synergistic effect of sildenafil and DOX on prostate cancer cell killing. Furthermore, treatment with sildenafil and DOX in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. The reduced tumor size was associated with amplified apoptotic cell death and increased expression of activated caspase 3. Doppler echocardiography showed that sildenafil treatment ameliorated DOX-induced left ventricular dysfunction. In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit. PMID:20884855

  2. Intravoxel incoherent motion diffusion-weighted imaging for monitoring chemotherapeutic efficacy in gastric cancer

    PubMed Central

    Song, Xiao-Li; Kang, Heoung Keun; Jeong, Gwang Woo; Ahn, Kyu Youn; Jeong, Yong Yeon; Kang, Yang Joon; Cho, Hye Jung; Moon, Chung Man

    2016-01-01

    AIM: To assess intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for monitoring early efficacy of chemotherapy in a human gastric cancer mouse model. METHODS: IVIM-DWI was performed with 12 b-values (0-800 s/mm2) in 25 human gastric cancer-bearing nude mice at baseline (day 0), and then they were randomly divided into control and 1-, 3-, 5- and 7-d treatment groups (n = 5 per group). The control group underwent longitudinal MRI scans at days 1, 3, 5 and 7, and the treatment groups underwent subsequent MRI scans after a specified 5-fluorouracil/calcium folinate treatment. Together with tumor volumes (TV), the apparent diffusion coefficient (ADC) and IVIM parameters [true water molecular diffusion coefficient (D), perfusion fraction (f) and pseudo-related diffusion coefficient (D*)] were measured. The differences in those parameters from baseline to each measurement (ΔTV%, ΔADC%, ΔD%, Δf% and ΔD*%) were calculated. After image acquisition, tumor necrosis, microvessel density (MVD) and cellular apoptosis were evaluated by hematoxylin-eosin (HE), CD31 and terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining respectively, to confirm the imaging findings. Mann-Whitney test and Spearman's correlation coefficient analysis were performed. RESULTS: The observed relative volume increase (ΔTV%) in the treatment group were significantly smaller than those in the control group at day 5 (ΔTVtreatment% = 19.63% ± 3.01% and ΔTVcontrol% = 83.60% ± 14.87%, P = 0.008) and day 7 (ΔTVtreatment% = 29.07% ± 10.01% and ΔTVcontrol% = 177.06% ± 63.00%, P = 0.008). The difference in ΔTV% between the treatment and the control groups was not significant at days 1 and 3 after a short duration of treatment. Increases in ADC in the treatment group (ΔADC%treatment, median, 30.10% ± 18.32%, 36.11% ± 21.82%, 45.22% ± 24.36%) were significantly higher compared with the control group (ΔADC%control, median, 4.98% ± 3.39%, 6.26% ± 3

  3. In vitro evaluation of antitumoral efficacy of catalase in combination with traditional chemotherapeutic drugs against human lung adenocarcinoma cells.

    PubMed

    de Oliveira, Valeska Aguiar; da Motta, Leonardo Lisbôa; De Bastiani, Marco Antônio; Lopes, Fernanda Martins; Müller, Carolina Beatriz; Gabiatti, Bernardo Papini; França, Fernanda Stapenhorst; Castro, Mauro Antônio Alves; Klamt, Fabio

    2016-08-01

    Lung cancer is the most lethal cancer-related disease worldwide. Since survival rates remain poor, there is an urgent need for more effective therapies that could increase the overall survival of lung cancer patients. Lung tumors exhibit increased levels of oxidative markers with altered levels of antioxidant defenses, and previous studies demonstrated that the overexpression of the antioxidant enzyme catalase (CAT) might control tumor proliferation and aggressiveness. Herein, we evaluated the effect of CAT treatment on the sensitivity of A549 human lung adenocarcinoma cells toward various anticancer treatments, aiming to establish the best drug combination for further therapeutic management of this disease. Exponentially growing A549 cells were treated with CAT alone or in combination with chemotherapeutic drugs (cisplatin, 5-fluorouracil, paclitaxel, daunorubicin, and hydroxyurea). CalcuSyn(®) software was used to assess CAT/drug interactions (synergism or antagonism). Growth inhibition, NFκB activation status, and redox parameters were also evaluated in CAT-treated A549 cells. CAT treatment caused a cytostatic effect, decreased NFκB activation, and modulated the redox parameters evaluated. CAT treatment exhibited a synergistic effect among most of the anticancer drugs tested, which is significantly correlated with an increased H2O2 production. Moreover, CAT combination caused an antagonism in paclitaxel anticancer effect. These data suggest that combining CAT (or CAT analogs) with traditional chemotherapeutic drugs, especially cisplatin, is a promising therapeutic strategy for the treatment of lung cancer.

  4. An MMP-2 Responsive Liposome Integrating Antifibrosis and Chemotherapeutic Drugs for Enhanced Drug Perfusion and Efficacy in Pancreatic Cancer.

    PubMed

    Ji, Tianjiao; Li, Suping; Zhang, Yinlong; Lang, Jiayan; Ding, Yanping; Zhao, Xiao; Zhao, Ruifang; Li, Yiye; Shi, Jian; Hao, Jihui; Zhao, Ying; Nie, Guangjun

    2016-02-10

    Fibrotic stroma, a critical character of pancreatic tumor microenvironment, provides a critical barrier against the penetration and efficacy of various antitumor drugs. Therefore, new strategies are urgently needed to alleviate the fibrotic mass and increase the drug perfusion within pancreatic cancer tissue. In our current work, we developed a β-cyclodextrin (β-CD) modified matrix metalloproteinase-2 (MMP-2) responsive liposome, integrating antifibrosis and chemotherapeutic drugs for regulation of pancreatic stellate cells (PSCs), a key source of the fibrosis, and targeted delivery of cytotoxic drugs for pancreatic cancer therapy. These liposomes disassembed into two functional parts upon MMP-2 cleavage at the tumor site. One part was constituted by the β-CDs and the antifibrosis drug pirfenidone, which was kept in the stroma and inhibited the expression of collagen I and TGF-β in PSCs, down-regulating the fibrosis and decreasing the stromal barrier. The other segment, the RGD peptide-modified-liposome loading the chemotherapeutic drug gemcitabine, targeted and killed pancreatic tumor cells. This integrated nanomedicine, showing an increased drug perfusion without any overt side effects, may provide a potential strategy for improvement of the pancreatic cancer therapy. PMID:26759926

  5. Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells.

    PubMed

    Wang, Fang; Chen, Yifan; Huang, Lihua; Liu, Tao; Huang, Yue; Zhao, Jianming; Wang, Xiaokun; Yang, Ke; Ma, Shaolin; Huang, Liyan; To, Kenneth Kin Wah; Gu, Yong; Fu, Liwu

    2015-12-01

    The overexpression of ATP-binding cassette (ABC) transporters is closely associated with the development of multidrug resistance (MDR) in certain types of cancer, which represents a formidable obstacle to the successful cancer chemotherapy. Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed the chemoresistance mediated by ABCB1, ABCG2 or ABCC1. Our results showed that cetuximab significantly enhanced the cytotoxicity of ABCB1 substrate agent in ABCB1-overexpressing MDR cells but had no effect in their parental drug sensitive cells and ABCC1, ABCG2 overexpressing cells. Furthermore, cetuximab markedly increased intracellular accumulation of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABCB1-overexpressing MDR cancer cells in a concentration-dependent manner. Cetuximab stimulated the ATPase activity but did not alter the expression level of ABCB1 or block phosphorylation of AKT and ERK. Interestingly, cetuximab decreased the cell membrane fluidity which was known to decrease the function of ABCB1. Our findings advocate further clinical investigation of combination chemotherapy of cetuximab and conventional chemotherapeutic drugs in ABCB1 overexpressing cancer patients.

  6. Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells

    PubMed Central

    Liu, Tao; Huang, Yue; Zhao, Jianming; Wang, Xiaokun; Yang, Ke; Ma, Shaolin; Huang, Liyan; Wah To, Kenneth Kin; Gu, Yong; Fu, Liwu

    2015-01-01

    The overexpression of ATP-binding cassette (ABC) transporters is closely associated with the development of multidrug resistance (MDR) in certain types of cancer, which represents a formidable obstacle to the successful cancer chemotherapy. Here, we investigated that cetuximab, an EGFR monoclonal antibody, reversed the chemoresistance mediated by ABCB1, ABCG2 or ABCC1. Our results showed that cetuximab significantly enhanced the cytotoxicity of ABCB1 substrate agent in ABCB1-overexpressing MDR cells but had no effect in their parental drug sensitive cells and ABCC1, ABCG2 overexpressing cells. Furthermore, cetuximab markedly increased intracellular accumulation of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABCB1-overexpressing MDR cancer cells in a concentration-dependent manner. Cetuximab stimulated the ATPase activity but did not alter the expression level of ABCB1 or block phosphorylation of AKT and ERK. Interestingly, cetuximab decreased the cell membrane fluidity which was known to decrease the function of ABCB1. Our findings advocate further clinical investigation of combination chemotherapy of cetuximab and conventional chemotherapeutic drugs in ABCB1 overexpressing cancer patients. PMID:26506420

  7. Chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract against chromium-induced testicular toxicity in rats.

    PubMed

    Sadek, K M

    2014-01-01

    This study was conducted to determine the mechanism underlying the chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract (MOLEE) against chromium-induced impairments of rat testes using biochemical methods. Twenty male Wistar rats were divided into four groups of five animals each. Group I (control), group II injected potassium dichromate (8 mg kg(-1) ) i.p., group III gastrogavaged MOLEE (500 mg kg(-1) ) p.o. and group IV received (potassium dichromate plus MOLEE) by the same doses for 60 days. After the blood samples were collected, the animals were sacrificed to determine the testicular antioxidant status and sperm parameters. The chromium-treated group exhibited a significant decrease in testicular antioxidant enzymatic activities, local immunity and sperm parameters as well as an increase in inflammatory markers when compared with the control and MOLEE-treated group. However, concurrent administration of chromium and MOLEE significantly ameliorated the chromium effects on the sperm parameters, local immunity, inflammatory markers and antioxidant enzymatic activities compared with rats exposed to chromium alone. This study concludes that chronic exposure to chromium produces clear testicular toxicity, which can either be prevented or at least decreased by concomitant administration of MOLEE. Interestingly, the metal ion chelation could attribute partly the antioxidant activities of MOLEE. PMID:24215114

  8. Chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract against chromium-induced testicular toxicity in rats.

    PubMed

    Sadek, K M

    2014-01-01

    This study was conducted to determine the mechanism underlying the chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract (MOLEE) against chromium-induced impairments of rat testes using biochemical methods. Twenty male Wistar rats were divided into four groups of five animals each. Group I (control), group II injected potassium dichromate (8 mg kg(-1) ) i.p., group III gastrogavaged MOLEE (500 mg kg(-1) ) p.o. and group IV received (potassium dichromate plus MOLEE) by the same doses for 60 days. After the blood samples were collected, the animals were sacrificed to determine the testicular antioxidant status and sperm parameters. The chromium-treated group exhibited a significant decrease in testicular antioxidant enzymatic activities, local immunity and sperm parameters as well as an increase in inflammatory markers when compared with the control and MOLEE-treated group. However, concurrent administration of chromium and MOLEE significantly ameliorated the chromium effects on the sperm parameters, local immunity, inflammatory markers and antioxidant enzymatic activities compared with rats exposed to chromium alone. This study concludes that chronic exposure to chromium produces clear testicular toxicity, which can either be prevented or at least decreased by concomitant administration of MOLEE. Interestingly, the metal ion chelation could attribute partly the antioxidant activities of MOLEE.

  9. Identification of plumbagin and sanguinarine as effective chemotherapeutic agents for treatment of schistosomiasis☆

    PubMed Central

    Zhang, Si-Ming; Coultas, Kristen A.

    2012-01-01

    Schistosomiasis, a snail-borne parasitic disease, affects more than 200 million people worldwide. Currently the treatment of schistosomiasis relies on a single therapy of praziquantel, a drug developed over 30 years ago. Thus, there is an urgent need to develop alternative antischistosomal drugs. In the pursuit of novel antischistosomal drugs, we examined the antischistosomal activities of 45 compounds that had been reported to exhibit antimicrobial and/or antiparasitic activities. Two plant-derived compounds, plumbagin and sanguinarine, were found to possess potent antischistosomal activities in vitro. For both the compounds, a concentration of 10 μM (equivalent to 1.88 μg/ml for plumbagin and 3.68 μg/ml for sanguinarine) resulted in 100% mortality at 48 h, which meets the World Health Organization’s (WHO) criterion of “hit” compounds for the control of schistosomiasis. Morphological changes and tegumental alterations of the dead worms treated by the two compounds were quite different. The significant morphological changes of worms after treatment by the two compounds suggest the two compounds target different biological pathways, both of which result in parasite’s death. This study provides evidence to suggest plumbagin and sanguinarine have real potential as effective alternative chemotherapeutic agents for the treatment of schistosomiasis. PMID:23641325

  10. NOVP: a novel chemotherapeutic regimen with minimal toxicity for treatment of Hodgkin's disease

    SciTech Connect

    Hagemeister, F.B.; Cabanillas, F.; Velasquez, W.S.; Meistrich, M.L.; Liang, J.C.; McLaughlin, P.; Redman, J.R.; Romaguera, J.E.; Rodriguez, M.A.; Swan, F. Jr. )

    1990-12-01

    Patients with early-staged Hodgkin's disease have had a higher relapse rate following radiotherapy alone if they have B symptoms, large mediastinal masses, hilar involvement, or stage III disease. From June 1988 to December 1989, 27 previously untreated patients with early-staged Hodgkin's disease with adverse features for disease-free survival received combined-modality therapy. Seventeen patients had stage I or II disease, 10 had stage III, 5 had B symptoms, 13 had large mediastinal masses, and 6 had peripheral masses measuring 10 cm or more in diameter. All patients initially received three cycles of a novel chemotherapeutic regimen combining Novantrone (mitoxantrone, American Cyanamid Company), vincristine, vinblastine, and prednisone (NOVP). Twenty-four patients with clinically staged I or II disease with adverse features or stage III disease did not undergo laparotomy; three patients had favorable stage I or II disease and at laparotomy had stage III disease. Radiotherapy-treatment fields depended on the extent of nodal involvement. Twenty-six patients completed all therapy as planned to complete remission (CR) and one of these has had progression; she is in second CR following additional radiotherapy. With a median follow-up of 12 months, all patients are alive. Tolerance to treatment was excellent with only grade 1 or 2 nausea, alopecia and myalgias, and brief myelosuppression. NOVP is an effective adjuvant chemotherapy regimen for inducing responses, with minimal toxicity, prior to definitive radiotherapy for patients with early-staged Hodgkin's disease.

  11. The DNA damage/repair cascade in glioblastoma cell lines after chemotherapeutic agent treatment.

    PubMed

    Annovazzi, Laura; Caldera, Valentina; Mellai, Marta; Riganti, Chiara; Battaglia, Luigi; Chirio, Daniela; Melcarne, Antonio; Schiffer, Davide

    2015-01-01

    Therapeutic resistance in glioblastoma multiforme (GBM) has been linked to a subpopulation of cells with stem cell-like properties, the glioma stem cells (GSCs), responsible for cancer progression and recurrence. This study investigated the in vitro cytotoxicity of three chemotherapeutics, temozolomide (TMZ), doxorubicin (Dox) and paclitaxel (PTX) on glioma cell lines, by analyzing the molecular mechanisms leading to DNA repair and cell resistance, or to cell death. The drugs were tested on 16 GBM cell lines, grown as neurospheres (NS) or adherent cells (AC), by studying DNA damage occurrence by Comet assay, the expression by immunofluorescence and western blotting of checkpoint/repair molecules and apoptosis. The three drugs were able to provoke a genotoxic injury and to inhibit dose- and time-dependently cell proliferation, more evidently in AC than in NS. The first cell response to DNA damage was the activation of the damage sensors (p-ATM, p-53BP1, γ-H2AX), followed by repair effectors; the expression of checkpoint/repair molecules appeared higher in NS than in AC. The non-homologous repair pathway (NHEJ) seemed more involved than the homologous one (HR). Apoptosis occurred after long treatment times, but only a small percentage of cells in NS underwent death, even at high drug concentration, whereas most cells survived in a quiescent state and resumed proliferation after drug removal. In tumor specimens, checkpoint/repair proteins were constitutively expressed in GBMs, but not in low-grade gliomas.

  12. Treatment of cancer using pulsed electric field in combination with chemotherapeutic agents or genes.

    PubMed

    Nishi, T; Dev, S B; Yoshizato, K; Kuratsu, J; Ushio, Y

    1997-03-01

    Electroporation is a standard laboratory technique originally developed for in vitro transfer of molecules into cells. It involves application of electrical pulses ranging from micro- to milliseconds that create transient pores in the cell membrane allowing intracellular access of exogenous molecules. This technique has been successfully applied to regress tumors in animal models by combining electroporation with chemotherapeutic agents--a process known as electrochemotherapy (ECT) which substantially enhance cytotoxicity of some antineoplastic agents. Recently ECT has moved into clinical arena and patients with cutaneous tumors and head and neck cancers have been treated very effectively with ECT. Parallel to ECT, a technique has also been developed which makes it possible to inject plasmid DNA and combine it with in vivo electroporation--electro--genetherapy (EGT)--to deliver in a highly efficient manner both marker and functional genes into target tissue and achieve gene expression. Thus, in vivo electroporation is contributing to the development of a new strategy for cancer treatment with both drugs and genes. PMID:9234068

  13. The anti-Fn14 antibody BIIB036 inhibits tumor growth in xenografts and patient derived primary tumor models and enhances efficacy of chemotherapeutic agents in multiple xenograft models.

    PubMed

    Michaelson, Jennifer S; Kelly, Rebecca; Yang, Lu; Zhang, Xiamei; Wortham, Kathleen; Joseph, Ingrid B J K

    2012-07-01

    Agonistic antibodies targeting Fn14, the receptor for TWEAK, have demonstrated anti-tumor activity in xenograft models. Herein, we further explore the therapeutic potential of the humanized anti-Fn14 agonistic antibody, BIIB036, as a single agent and in combination with standard of care cancer therapeutics. Pharmacokinetic studies of BIIB036 in tumor-bearing mice revealed a half-life of approximately three days suggesting twice a week dosing would be necessary to maintain efficacy. However, in multiple xenograft models, BIIB036 treatment resulted in extended tumor growth inhibition up to 40-50 d following cessation of dosing, suggesting that frequent administration of BIIB036 may not be necessary to maintain prolonged anti-tumor activity. Subsequent xenograft studies revealed that maximal efficacy was achieved with BIIB036 dosing once every two weeks, by either intraperitoneal or subcutaneous administration. Xenograft tumors that were initially treated with BIBI036 and then re-grew up to 1000 mm³ following cessation of the first cycle of treatment remained sensitive to a second cycle of treatment. BIIB036 was also evaluated in patient derived primary colon tumor models, where efficacy compared favorably with a standard of care agent. Lastly, BIIB036 enhanced the efficacy of several standard of care chemotherapeutics, including paclitaxel in MDA-MBA-231 breast tumor xenografts, paclitaxel or carboplatin in HOP62 non-small cell lung xenografts, and 5-FU in NCI-N87 gastric xenografts, with no overlapping toxicities. These studies thus establish BIIB036 as a promising therapeutic agent with durable anti-tumor activity in human xenografts as well as patient derived primary tumor models, and enhanced activity and tolerability in combination with standard of care chemotherapeutics. Taken together, the data presented herein suggest that BIIB036 warrants evaluation in the clinic.

  14. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  15. Arylimidamide DB766, a Potential Chemotherapeutic Candidate for Chagas' Disease Treatment

    PubMed Central

    Batista, Denise da Gama Jaén; Batista, Marcos Meuser; Oliveira, Gabriel Melo de; Amaral, Patrícia Borges do; Lannes-Vieira, Joseli; Britto, Constança Carvalho; Junqueira, Angela; Lima, Marli Maria; Romanha, Alvaro José; Sales Junior, Policarpo Ademar; Stephens, Chad E.; Boykin, David W.; Soeiro, Maria de Nazaré Correia

    2010-01-01

    Chagas' disease, a neglected tropical illness for which current therapy is unsatisfactory, is caused by the intracellular parasite Trypanosoma cruzi. The goal of this work is to investigate the in vitro and in vivo effects of the arylimidamide (AIA) DB766 against T. cruzi. This arylimidamide exhibits strong trypanocidal activity and excellent selectivity for bloodstream trypomastigotes and intracellular amastigotes (Y strain), giving IC50s (drug concentrations that reduce 50% of the number of the treated parasites) of 60 and 25 nM, respectively. DB766 also exerts striking effects upon different parasite stocks, including those naturally resistant to benznidazole, and displays higher activity in vitro than the reference drugs. By fluorescent and transmission electron microscopy analyses, we found that this AIA localizes in DNA-enriched compartments and induces considerable damage to the mitochondria. DB766 effectively reduces the parasite load in the blood and cardiac tissue and presents efficacy similar to that of benznidazole in mouse models of T. cruzi infection employing the Y and Colombian strains, using oral and intraperitoneal doses of up to 100 mg/kg/day that were given after the establishment of parasite infection. This AIA ameliorates electrocardiographic alterations, reduces hepatic and heart lesions induced by the infection, and provides 90 to 100% protection against mortality, which is similar to that provided by benznidazole. Our data clearly show the trypanocidal efficacy of DB766, suggesting that this AIA may represent a new lead compound candidate to Chagas' disease treatment. PMID:20457822

  16. Nilotinib enhances the efficacy of conventional chemotherapeutic drugs in CD34⁺CD38⁻ stem cells and ABC transporter overexpressing leukemia cells.

    PubMed

    Wang, Fang; Wang, Xiao-Kun; Shi, Cheng-Jun; Zhang, Hui; Hu, Ya-Peng; Chen, Yi-Fan; Fu, Li-Wu

    2014-03-19

    Incomplete chemotherapeutic eradication of leukemic CD34⁺CD38⁻ stem cells is likely to result in disease relapse. The purpose of this study was to evaluate the effect of nilotinib on eradicating leukemia stem cells and enhancing the efficacy of chemotherapeutic agents. Our results showed that ABCB1 and ABCG2 were preferentially expressed in leukemic CD34⁺CD38⁻ cells. Nilotinib significantly enhanced the cytotoxicity of doxorubicin and mitoxantrone in CD34⁺CD38⁻ cells and led to increased apoptosis. Moreover, nilotinib strongly reversed multidrug resistance and increased the intracellular accumulation of rhodamine 123 in primary leukemic blasts overexpressing ABCB1 and/or ABCG2. Studies with ABC transporter-overexpressing carcinoma cell models confirmed that nilotinib effectively reversed ABCB1- and ABCG2-mediated drug resistance, while showed no significant reversal effect on ABCC1- and ABCC4-mediated drug resistance. Results from cytotoxicity assays showed that CD34⁺CD38⁻ cells exhibited moderate resistance (2.41-fold) to nilotinib, compared with parental K562 cells. Furthermore, nilotinib was less effective in blocking the phosphorylation of Bcr-Abl and CrkL (a substrate of Bcr-Abl kinase) in CD34⁺CD38⁻ cells. Taken together, these data suggest that nilotinib particularly targets CD34⁺CD38⁻ stem cells and MDR leukemia cells, and effectively enhances the efficacy of chemotherapeutic drugs by blocking the efflux function of ABC transporters.

  17. Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas

    PubMed Central

    KITA, HIROKO; OKAMOTO, KEISEI; KUSHIMA, RYOJI; KAWAUCHI, AKIHIRO; CHANO, TOKUHIRO

    2015-01-01

    Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is used as a solvent in biological studies and as a vehicle for drug therapy. The present study was designed to evaluate the potential effects of DMSO as a solvent in the treatment of testicular embryonal carcinomas (ECs). DMSO was applied to two human EC cell lines (NEC8 and NEC14), with the treated cells evaluated in relation to cisplatin (CDDP) resistance, differentiation (using Vimentin, Fibronectin, TRA-1-60, and SSEA-1 and -3 as markers) and stemness (denoted by expression of SOX2 and OCT3/4). Furthermore, DNA methyltransferase (DNMT-1, -3A and -3L) expression and methylation status were analyzed. DMSO induced resistance to CDDP, aberrant differentiation and reduction of stemness-related markers in each of the EC cell lines. The expression levels of DNMT-3L and -3A were reduced in response to DMSO, while this treatment also affected DNA methylation. The data demonstrated that DMSO perturbed differentiation, reduced stemness and induced resistance to CDDP in human EC cells. Therefore, DMSO could reduce drug efficacy against EC cells and its use should be carefully managed in the clinical application of chemotherapy. PMID:26622550

  18. Crystal structure and chemotherapeutic efficacy of the novel compound, gallium tetrachloride betaine, against breast cancer using nanotechnology.

    PubMed

    Salem, Ahmed; Noaman, Eman; Kandil, Eman; Badawi, Abdelfattah; Mostafa, Nihal

    2016-08-01

    The objective of this study was to investigate the antitumor efficacy of a novel synthesized compound, betaine gallium-tetrachloride (BTG), alone or combined with ZnO-nanoparticles (BTG + ZnO-NPs) on the incidence of 7, 12-dimethylbenz-anthrathene-induced mammary tumor in female rats. Crystal and molecular structure of the prepared BTG were identified using X-ray crystallography. In vitro study revealed BTG more cytotoxic than BTG + ZnO-NPs on human breast cancer (MCF-7) cell line. In vivo study demonstrated that the blood antioxidant status of tumor-bearing rats (DMBA group) was significantly lower than normal noticeable by a significant decrease in GSH content, GPx, SOD, and CAT activities associated with a significantly high MDA content. Both treatments have significantly elevated SOD and CAT activities with a concomitant decrease of MDA level compared to DMBA group. However, BTG + ZnO-NPs accentuated the decrease of GSH regarding DMBA group. The results showed also that both treatments significantly activate caspase-3 enzyme and apoptosis in mammary glands. Their administration to tumor-bearing rats was found to significantly reduce plasma iron and iron-binding capacity (TIBC) compared to DMBA group. Regarding liver function, both treatments significantly reduced the increase of ALT and AST activities compared to DMBA group. However, BTG + ZnO-NPs decreased albumin below normal level. Histopathological studies showed that normalization of tissue structures was higher in BTG than BTG + ZnO-NPs treatment. According to the results obtained, it is observed that the antitumor effect of BTG alone was as strong as BTG + ZnO-NPs and even more efficient in some aspects accordingly, a combination is not needed. Thus, the novel synthetic gallium derivatives may potentially present a new hope for the development of breast cancer therapeutics, which should attract further scientific and pharmaceutical interest. PMID:26894603

  19. NOTCH1 inhibition enhances the efficacy of conventional chemotherapeutic agents by targeting head neck cancer stem cell

    PubMed Central

    Zhao, Zhi-Li; Zhang, Lu; Huang, Cong-Fa; Ma, Si-Rui; Bu, Lin-Lin; Liu, Jian-Feng; Yu, Guang-Tao; Liu, Bing; Gutkind, J. Silvio; Kulkarni, Ashok B.; Zhang, Wen-Feng; Sun, Zhi-Jun

    2016-01-01

    Cancer stem cells (CSCs) are considered responsible for tumor initiation and chemoresistance. This study was aimed to investigate the possibility of targeting head neck squamous cell carcinoma (HNSCC) by NOTCH1 pathway inhibition and explore the synergistic effect of combining NOTCH inhibition with conventional chemotherapy. NOTCH1/HES1 elevation was found in human HNSCC, especially in tissue post chemotherapy and lymph node metastasis, which is correlated with CSCs markers. NOTCH1 inhibitor DAPT (GSI-IX) significantly reduces CSCs population and tumor self-renewal ability in vitro and in vivo. Flow cytometry analysis showed that NOTCH1 inhibition reduces CSCs frequency either alone or in combination with chemotherapeutic agents, namely, cisplatin, docetaxel, and 5-fluorouracil. The combined strategy of NOTCH1 blockade and chemotherapy synergistically attenuated chemotherapy-enriched CSC population, promising a potential therapeutic exploitation in future clinical trial. PMID:27108536

  20. Multiphysics and Multiscale Analysis for Chemotherapeutic Drug

    PubMed Central

    Zhang, Linan; Kim, Sung Youb; Kim, Dongchoul

    2015-01-01

    This paper presents a three-dimensional dynamic model for the chemotherapy design based on a multiphysics and multiscale approach. The model incorporates cancer cells, matrix degrading enzymes (MDEs) secreted by cancer cells, degrading extracellular matrix (ECM), and chemotherapeutic drug. Multiple mechanisms related to each component possible in chemotherapy are systematically integrated for high reliability of computational analysis of chemotherapy. Moreover, the fidelity of the estimated efficacy of chemotherapy is enhanced by atomic information associated with the diffusion characteristics of chemotherapeutic drug, which is obtained from atomic simulations. With the developed model, the invasion process of cancer cells in chemotherapy treatment is quantitatively investigated. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of chemotherapy treatment. PMID:26491672

  1. Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer

    PubMed Central

    Chen, Jing; Guo, Jiawei; Chen, Zhi; Wang, Jieqiong; Liu, Mingyao; Pang, Xiufeng

    2016-01-01

    Gastric cancer, highly dependent on tumor angiogenesis, causes uncontrolled lethality, in part due to chemoresistance. Here, we demonstrate that linifanib (ABT-869), a novel multi-targeted receptor tyrosine kinase inhibitor, markedly augments cytotoxicity of chemotherapies in human gastric cancer. ABT-869 and chemotherapeutic agents exhibited a strong synergy to inhibit the viability of several gastric cancer cell lines, with combination index values ranging from 0.017 to 0.589. Additionally, the combination of ABT-869 and chemotherapeutic agents led to remarkable suppression of vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo. Importantly, in a preclinical gastric cancer xenograft mouse model, drug co-treatments led to increased mouse survival as well as a synergistic reduction in tumor size and the inhibition of tumor angiogenesis. Mechanistic studies further revealed that all of the co-treatments containing ABT-869 resulted in decreased activation of the VEGF receptor, the epidermal growth factor receptor and the insulin growth factor receptor. Inhibition of these receptor tyrosine kinases consequently attenuated the activation of the downstream AKT/mTOR signaling pathway both in cultured gastric cancer cells and in gastric cancer xenografts. Collectively, our findings suggest that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer. PMID:27387652

  2. The over-expression of survivin enhances the chemotherapeutic efficacy of YM155 in human hepatocellular carcinoma.

    PubMed

    Xia, Hongping; Chen, Jianxiang; Shi, Ming; Deivasigamani, Amudha; Ooi, London Lucien P J; Hui, Kam M

    2015-03-20

    Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. The inability of chemotherapeutic drugs to selectively target HCC tumor cells because of their predominant resistant phenotype to most conventional anticancer agents bestows a major obstacle for the clinical management of HCC. In this report, we have examined and demonstrated the remarkable heterogeneity of expression of survivin and its phosphorylated active form (p-survivin) in HCC patients' tissues and cell lines. Furthermore, the expression of survivin and p-survivin in HCC cell lines was found to be associated with response to the small-molecule survivin suppressant YM155. Therefore, in the HCC cell lines that express elevated level of survivin and p-survivin, YM155 efficiently inhibited their proliferation, induced cell cycle arrest and apoptosis resulting in DNA damage through the dysregulation of cell-cycle checkpoint-related regulatory genes. Importantly, YM155 yielded significantly better therapeutic effect than sorafenib when tested in an orthotopic mouse model using patient-derived HCC xenografts with elevated survivin and p-survivin expression. Our results clearly demonstrated that the level of survivin and p-survivin expression could serve as molecular predictive biomarkers to select potential YM155-responsive patients, in a move towards delivering precision medicine for HCC patients.

  3. Effects of Early Chemotherapeutic Treatment on Learning in Adolescent Mice: Implications for Cognitive Impairment and Remediation in Childhood Cancer Survivors

    PubMed Central

    Bisen-Hersh, Emily B.; Hineline, Philip N.; Walker, Ellen A.

    2013-01-01

    Purpose Among children diagnosed with acute lymphoblastic leukemia (ALL) and given chemotherapy-only treatment, 40-70% of survivors experience neurocognitive impairment. The present study used a preclinical mouse model to investigate the effects of early exposure to common ALL chemotherapeutics methotrexate (MTX) and cytarabine (Ara-C) on learning and memory. Experimental Design Pre-weanling mouse pups were treated on postnatal day (PND) 14, 15, and 16 with saline, MTX, Ara-C, or a combination of MTX and Ara-C. Nineteen days following treatment (PND 35), behavioral tasks measuring different aspects of learning and memory were administered. Results Significant impairment in acquisition and retention over both short (1h) and long (24h) intervals, as measured by autoshaping and novel object recognition tasks, were found following treatment with MTX and Ara-C. Similarly, a novel conditional discrimination task revealed impairment in acquisition for chemotherapy-treated mice. No significant group differences were found following the extensive training component of this task, with impairment following the rapid training component occurring only for the highest MTX and Ara-C combination group. Conclusions Findings are consistent with clinical studies suggesting that childhood cancer survivors are slower at learning new information and primarily exhibit deficits in memory years after successful completion of chemotherapy treatment. The occurrence of mild deficits on a novel conditional discrimination task suggests that chemotherapy-induced cognitive impairment may be ameliorated through extensive training or practice. PMID:23596103

  4. Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

    SciTech Connect

    DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

    1985-04-01

    The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin.

  5. Ethanol Extract of Oldenlandia diffusa – an Effective Chemotherapeutic for the Treatment of Colorectal Cancer in Humans

    PubMed Central

    Lee, Soojin; Shim, Ji Hwan; Gim, Huijin; Park, Hyun Soo

    2016-01-01

    Objectives: Oldenlandia diffusa is traditionally used to relieve the symptoms of and to treat various diseases, but its anti-cancer activity has not been well studied. In the present study, the authors investigated the anti-cancer effects of an ethanol extract of Oldenlandia diffusa (EOD) on HT-29 human adenocarcinoma cells. Methods: Cells were treated with different concentrations of an EOD, and cell death was assessed by using a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Analyses of the sub G1 peak, the caspase-3 and -9 activities, and the mitochondrial membrane depolarizations were conducted to confirm cell death by apoptosis. Also, intracellular reactive oxygen species (ROS) generation was determined using carboxy-H2DCFDA (5-(and-6)-carboxy-20,70-dichlorodihydrofluorescein diacetate). Results: EOD inhibited the proliferation of HT-29 cells for 24 hours by 78.6% ± 8.1% at 50 μg/mL, 74.4% ± 4.6% at 100 μg/mL, 65.9% ± 5.2% at 200 μg/mL, 51.4% ± 6.2% at 300 μg/mL, and by 41.7% ± 8.9% at 400 μg/mL, and treatment for 72 hours reduced the proliferation at the corresponding concentrations by 43.3% ± 8.8%, 24.3 ± 5.1 mV, 13.5 ± 3.2 mV, 6.5 ± 2.3 mV, and by 2.6 ± 2.3 mV. EOD increased the number of cells in the sub-G1 peak in a dose-dependent manner. The mitochondrial membrane depolarization was elevated by EOD. Also, caspase activities were dose-dependently elevated in the presence of EOD, and these activities were repressed by a pan-caspase inhibitor (zVAD-fmk). The ROS generation was significantly increased by EOD and N-acetyl-L-cysteine (NAC; a ROS scavenger) remarkably abolished EOD-induced cell death. In addition, a combination of sub-optimal doses of EOD and chemotherapeutic agents noticeably suppressed the growth of HT-29 cancer cells. Conclusion: These results indicate that EOD might be an effective chemotherapeutic for the treatment of human colorectal cancer. PMID:27280050

  6. [Nutritional and defunctionalized jejunostomy in the chemotherapeutic treatment of gastric non-Hodgkin's lymphoma. Preliminary experience].

    PubMed

    Messinetti, S; Martelli, M; Giacomelli, L; Brescia, A; Miglietta, A M; Pulcini, A; Finizio, R; Porcelli, C

    1993-01-01

    The authors propose a jejunostomy on an omega loop distal to the Treitz ligament as a treatment for unresectable gastric lymphomas. The rationale is to provide nutritional support during chemotherapy in a situation when the stomach is defunctionalised. As assessed by clinical, morphological and biological parameters, the association of chemotherapy and jejunostomy may represent a valid therapeutical strategy for patients considered unresectable.

  7. Treatment Outcomes and Efficacy in the Schools.

    ERIC Educational Resources Information Center

    Logemann, Jeri A.

    1998-01-01

    Introduces six articles which address treatment outcomes and efficacy in audiology and speech-language pathology in the schools. Stresses the importance of practitioners participating in studies of treatment outcomes and efficacy to demonstrate that their evaluations and treatments make a significant difference to individuals served. (DB)

  8. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

    PubMed

    Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

    2015-01-01

    6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

  9. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

    PubMed Central

    Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

    2015-01-01

    6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

  10. Glioma cell VEGFR-2 confers resistance to chemotherapeutic and antiangiogenic treatments in PTEN-deficient glioblastoma.

    PubMed

    Kessler, Tobias; Sahm, Felix; Blaes, Jonas; Osswald, Matthias; Rübmann, Petra; Milford, David; Urban, Severino; Jestaedt, Leonie; Heiland, Sabine; Bendszus, Martin; Hertenstein, Anne; Pfenning, Philipp-Niclas; Ruiz de Almodóvar, Carmen; Wick, Antje; Winkler, Frank; von Deimling, Andreas; Platten, Michael; Wick, Wolfgang; Weiler, Markus

    2015-10-13

    Loss of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a prerequisite for tumor cell-specific expression of vascular endothelial growth factor receptor (VEGFR)-2 in glioblastoma defining a subgroup prone to develop evasive resistance towards antiangiogenic treatments. Immunohistochemical analysis of human tumor tissues showed VEGFR-2 expression in glioma cells in 19% of specimens examined, mainly in the infiltration zone. Glioma cell VEGFR-2 positivity was restricted to PTEN-deficient tumor specimens. PTEN overexpression reduced VEGFR-2 expression in vitro, as well as knock-down of raptor or rictor. Genetic interference with VEGFR-2 revealed proproliferative, antiinvasive and chemoprotective functions for VEGFR-2 in glioma cells. VEGFR-2-dependent cellular effects were concomitant with activation of 'kappa-light-chain-enhancer' of activated B-cells, protein kinase B, and N-myc downstream regulated gene 1. Two-photon in vivo microscopy revealed that expression of VEGFR-2 in glioma cells hampers antiangiogenesis. Bevacizumab induces a proinvasive response in VEGFR-2-positive glioma cells. Patients with PTEN-negative glioblastomas had a shorter survival after initiation of bevacizumab therapy compared with PTEN-positive glioblastomas. Conclusively, expression of VEGFR-2 in glioma cells indicates an aggressive glioblastoma subgroup developing early resistance to temozolomide or bevacizumab. Loss of PTEN may serve as a biomarker identifying those tumors upfront by routine neuropathological methods.

  11. Natural and Synthetic Flavonoids: Structure-Activity Relationship and Chemotherapeutic Potential for the Treatment of Leukemia.

    PubMed

    Menezes, José C J M D S; Orlikova, Barbora; Morceau, Franck; Diederich, Marc

    2016-07-29

    Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family. PMID:26463658

  12. Identification of novel markers that demarcate the nucleolus during severe stress and chemotherapeutic treatment.

    PubMed

    Su, Haitong; Kodiha, Mohamed; Lee, Sunghoon; Stochaj, Ursula

    2013-01-01

    The nucleolus, the ribosomal factory of the cell, has emerged as a key player that regulates many aspects of cell biology. Several thousand proteins associate at least transiently with nucleoli, thereby generating a highly dynamic compartment with a protein profile which is sensitive to changes in cell physiology and pharmacological agents. Powerful tools that reliably demarcate the nucleoli are a prerequisite to measure their composition and activities. Previously, we developed quantitative methods to measure fluorescently labeled molecules in nucleoli. While these tools identify nucleoli under control and mild stress conditions, the accurate detection of nucleolar boundaries under harsh experimental conditions is complicated by the lack of appropriate markers for the nucleolar compartment. Using fluorescence microscopy we have now identified new marker proteins to detect nucleoli upon (a) severe stress and (b) drug treatments that trigger a pronounced reorganization of nucleoli. Our results demonstrate that nucleolin is an ideal marker to delimit nucleoli when cells are exposed to heat or oxidative stress. Furthermore, we show for the first time that cellular apoptosis susceptibility protein (CAS) and human antigen R protein (HuR) are excluded from nucleoli and can be employed to delimit these compartments under severe conditions that redistribute major nucleolar proteins. As proof-of-principle, we used these markers to demarcate nucleoli in cells treated with pharmacological compounds that disrupt the nucleolar organization. Furthermore, to gain new insights into the biology of the nucleolus, we applied our protocols and quantified stress- and drug-induced changes in nucleolar organization and function. Finally, we show that CAS, HuR and nucleolin not only identify nucleoli in optical sections, but are also suitable to demarcate the nucleolar border following 3D reconstruction. Taken together, our studies present novel marker proteins that delimit nucleoli with

  13. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma.

    PubMed

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG.

  14. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

    PubMed Central

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  15. PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma.

    PubMed

    Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

    2015-01-01

    The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

  16. Improving chemotherapeutic efficiency in acute myeloid leukemia treatments by chemically synthesized peptide interfering with CXCR4/CXCL12 axis

    PubMed Central

    Li, Xiaojin; Guo, Hua; Duan, Hongyang; Yang, Yanlian; Meng, Jie; Liu, Jian; Wang, Chen; Xu, Haiyan

    2015-01-01

    Bone marrow stroma can protect acute myeloid leukemia (AML) cells against chemotherapeutic agents and provide anti-apoptosis and chemoresistance signals through secreting chemokine CXCL12 to activate its receptor CXCR4 on AML cells, resulting in minimal residual leukemia and relapse. Therefore disrupting the CXCR4/CXCL12 axis with antagonists is of great significance for improving chemosensitivity and decreasing relapse rate. In a previous study, we reported a novel synthetic peptide E5 with its remarkable effect on inhibiting CXCR4/CXCL12-mediated adhesion and migration of AML cells. Here we presented E5’s capacity of enhancing the therapeutic efficiency of various chemotherapeutics on AML in vitro and in vivo. Results showed that E5 can diminish bone marrow stromal cell-provided protection to leukemia cells, significantly increasing the apoptosis induced by various chemotherapeutics in multiple AML cell lines. In an AML mouse xenograft model, E5 induced 1.84-fold increase of circulating AML cells out of protective stroma niche. Combined with vincristine or cyclophosphamide, E5 inhibited infiltration of AML cells into bone marrow, liver and spleen, as well as prolonged the lifespan of AML mice compared with mice treated with chemotherapy alone. In addition, E5 presented no toxicity in vivo according to the histological analysis and routine clinical parameters of serum analysis. PMID:26538086

  17. Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, TAS-102, with Oxaliplatin on Human Colorectal and Gastric Cancer Xenografts.

    PubMed

    Nukatsuka, Mamoru; Nakagawa, Fumio; Takechi, Teiji

    2015-09-01

    TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine (FTD) and the thymidine phosphorylase inhibitor tipiracil hydrochloride (at a molar ratio of 1:0.5) that was approved in Japan in 2014 for the treatment of unresectable advanced or recurrent colorectal cancer. In the present study, the enhancement of therapeutic efficacy using a combination of TAS-102 and oxaliplatin was evaluated in a xenograft-bearing nude mouse model of colorectal and gastric cancer. TAS-102 was orally administered twice-a-day from day 1 to 14, and oxaliplatin was administered intravenously on days 1 and 8. The in vivo growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, was estimated based on the period required to reach a tumor volume five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and RTV5 in mice administered TAS-102 with oxaliplatin were significantly superior to those associated with either monotherapy in mice with colorectal (HCT 116, SW-48; p<0.001) and gastric cancer (SC-2, MKN74; p<0.001). MKN74/5FU, a 5-fluorouracil-resistant MKN74 sub-line, was sensitive to both FTD and oxaliplatin in vitro. In vivo, TAS-102 alone was effective in MKN74/5FU, and its anti-tumor activity was significantly enhanced in combination with oxaliplatin (p<0.001). No significant decrease in body weight or toxicity was observed compared to either monotherapy. The present pre-clinical findings indicate that combination of TAS-102 and oxaliplatin is a promising treatment option for colorectal or gastric cancer, and can be utilized in both chemo-naïve tumors and recurrent tumors after 5-fluorouracil treatment.

  18. 24-h Efficacy of Glaucoma Treatment Options.

    PubMed

    Konstas, Anastasios G P; Quaranta, Luciano; Bozkurt, Banu; Katsanos, Andreas; Garcia-Feijoo, Julian; Rossetti, Luca; Shaarawy, Tarek; Pfeiffer, Norbert; Miglior, Stefano

    2016-04-01

    Current management of glaucoma entails the medical, laser, or surgical reduction of intraocular pressure (IOP) to a predetermined level of target IOP, which is commensurate with either stability or delayed progression of visual loss. In the published literature, the hypothesis is often made that IOP control implies a single IOP measurement over time. Although the follow-up of glaucoma patients with single IOP measurements is quick and convenient, such measurements often do not adequately reflect the untreated IOP characteristics, or indeed the quality of treated IOP control during the 24-h cycle. Since glaucoma is a 24-h disease and the damaging effect of elevated IOP is continuous, it is logical that we should aim to understand the efficacy of all treatment options throughout the 24-h period. This article first reviews the concept and value of diurnal and 24-h IOP monitoring. It then critically evaluates selected available evidence on the 24-h efficacy of medical, laser and surgical therapy options. During the past decade several controlled trials have significantly enhanced our understanding on the 24-h efficacy of all glaucoma therapy options. Nevertheless, more long-term evidence is needed to better evaluate the 24-h efficacy of glaucoma therapy and the precise impact of IOP characteristics on glaucomatous progression and visual prognosis.

  19. Treatment efficacy: hearing loss in children.

    PubMed

    Carney, A E; Moeller, M P

    1998-02-01

    This article provides a review of the topic of treatment efficacy for children with hearing loss. Efficacy is related to a wide range of treatment goals in the areas of sensory and perceptual skill development, language development (regardless of communication modality), speech-production skill development, academic performance, and social-emotional growth. Topics addressed in this article include (a) the definition of hearing loss in children; (b) incidence and prevalence data; (c) the effects of childhood hearing loss on daily life, including language and literacy, speech perception and production, socialization and family dynamics; (d) the role of audiologists and speech-language pathologists in managing children with hearing loss; and (e) a summary of pertinent efficacy research for children with hearing loss. The analysis of the available research suggests that (a) early intervention for children who are deaf or hard of hearing has long-term positive effects on overall development; (b) a variety of communication modalities exist for this population, and research to date has been more descriptive than prognostic on the choice of modality; (c) sensory aids (hearing aids, tactile aids, and cochlear implants) provide different degrees of benefit for children in the areas of speech perception, production, and language development, depending upon the extent of their hearing loss; (d) few studies have addressed rates of learning and long-term outcomes, but existing data suggest that enriched programs provide some children with hearing loss with the ability to overcome developmental lags in language and academic skills. PMID:9493747

  20. Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells

    PubMed Central

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David Lawson

    2016-01-01

    Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient’s treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research. PMID:27186409

  1. Potentiation of chemotherapeutics by bromelain and N-acetylcysteine: sequential and combination therapy of gastrointestinal cancer cells.

    PubMed

    Amini, Afshin; Masoumi-Moghaddam, Samar; Ehteda, Anahid; Liauw, Winston; Morris, David Lawson

    2016-01-01

    Intraperitoneal chemotherapy together with cytoreductive surgery is the standard of care for a number of peritoneal surface malignancies. However, this approach fails to maintain the complete response and disease recurs due to microscopic residual disease. Although safer than systemic chemotherapy regimens, locoregional treatment with chemotherapeutics can induce toxicity which is a major concern affecting the patient's treatment protocol and outcome. For an enhanced treatment efficacy, efforts should be made to maximize cytotoxic effects of chemotherapeutic agents on tumor cells while minimizing their toxic effects on host cells. Bromelain and N-acetylcysteine are two natural agents with good safety profiles shown to have anti-cancer effects. However, their interaction with chemotherapeutics is unknown. In this study, we investigated if these agents have the potential to sensitize in vitro gastrointestinal cancer models to cisplatin, paclitaxel, 5-fluorouracil, and vincristine. The drug-drug interaction was also analyzed. Our findings suggest that combination of bromelain and N-acetylcysteine with chemotherapeutic agents could give rise to an improved chemotherapeutic index in therapeutic approaches to peritoneal surface malignancies of gastrointestinal origin so that maximum benefits could result from less toxic and more patient-friendly doses. This represents a potentially efficacious strategy for the enhancement of microscopic cytoreduction and is a promising area for future research.

  2. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer.

    PubMed

    Niu, J; Xue, A; Chi, Y; Xue, J; Wang, W; Zhao, Z; Fan, M; Yang, C H; Shao, Z-M; Pfeffer, L M; Wu, J; Wu, Z-H

    2016-03-10

    Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The upregulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription but also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction had a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis.

  3. Induction of miRNA-181a by genotoxic treatments promotes chemotherapeutic resistance and metastasis in breast cancer

    PubMed Central

    Chi, Yayun; Xue, Jingyan; Wang, Wei; Zhao, Ziqin; Fan, Meiyun; Yang, Chuan He; Shao, Zhi-ming; Pfeffer, Lawrence M.; Wu, Jiong; Wu, Zhao-Hui

    2015-01-01

    Acquired therapeutic resistance is the major drawback to effective systemic therapies for cancers. Aggressive triple-negative breast cancers (TNBC) develop resistance to chemotherapies rapidly, whereas the underlying mechanisms are not completely understood. Here we show that genotoxic treatments significantly increased the expression of miR-181a in TNBC cells, which enhanced TNBC cell survival and metastasis upon Doxorubicin treatment. Consistently, high miR-181a level associated with poor disease free survival and overall survival after treatments in breast cancer patients. The up-regulation of miR-181a was orchestrated by transcription factor STAT3 whose activation depended on NF-κB-mediated IL-6 induction in TNBC cells upon genotoxic treatment. Intriguingly, activated STAT3 not only directly bound to MIR181A1 promoter to drive transcription, it also facilitated the recruitment of MSK1 to the same region where MSK1 promoted a local active chromatin state by phosphorylating histone H3. We further identified BAX as a direct functional target of miR-181a, whose suppression decreased apoptosis and increased invasion of TNBC cells upon Dox treatment. These results were further confirmed by evidence that suppression of miR-181a significantly enhanced therapeutic response and reduced lung metastasis in a TNBC orthotopic model. Collectively, our data suggested that miR-181a induction played a critical role in promoting therapeutic resistance and aggressive behavior of TNBC cells upon genotoxic treatment. Antagonizing miR-181a may serve as a promising strategy to sensitize TNBC cells to chemotherapy and mitigate metastasis. PMID:26028030

  4. Direct chemotherapeutic dual drug delivery through intra-articular injection for synergistic enhancement of rheumatoid arthritis treatment

    PubMed Central

    Reum Son, A; Kim, Da Yeon; Hun Park, Seung; Yong Jang, Ja; Kim, Kyungsook; Ju Kim, Byoung; Yun Yin, Xiang; Ho Kim, Jae; Hyun Min, Byoung; Keun Han, Dong; Suk Kim, Moon

    2015-01-01

    The effectiveness of systemic rheumatoid arthritis (RA) treatments is limited by difficulties in achieving therapeutic doses within articular joints. We evaluated the ability of intra-articular administration of injectable formulations to synergistically enhance repair of RA joints. Methotrexate-loaded hyaluronic acid (Met-HA), dexamethasone-loaded microcapsules (Dex-M), and Dex-M dispersed inside Met-HA were prepared as viscous emulsions and injected into articular joints using a needle to form a drug depot. By near-infrared (NIR) fluorescence imaging, we confirmed the local release of NIR from the depot injected into the articular joint over an extended period. In comparison with the subjects treated with Met-HA or Dex-M alone, subjects treated simultaneously with Met-HA and Dex-M exhibited faster and more significant RA repair. Collectively, these results indicated that the drug depot formed after intra-articular injection of Met-HA/Dex-M induced long-lasting drug release and allowed Met and Dex to effectively act in the articular joint, resulting in enhanced RA repair. PMID:26424611

  5. Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer

    PubMed Central

    Puhalla, Shannon; Brufsky, Adam

    2008-01-01

    Taxane therapy is commonly used in the treatment of metastatic breast cancer. However, most patients will eventually become refractory to these agents. Ixabepilone is a newly approved chemotherapeutic agent for the treatment of metastatic breast cancer. Although it targets microtubules similarly to docetaxel and paclitaxel, ixabepilone has activity in patients that are refractory to taxanes. This review summarizes the pharmacology of ixapebilone and clinical trials with the drug both as a single agent and in combination. Data were obtained using searches of PubMed and abstracts of the annual meetings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium from 1995 to 2008. Ixapebilone is a semi-synthetic analog of epothilone B that acts to induce apoptosis of cancer cells via the stabilization of microtubules. Phase I clinical trials have employed various dosing schedules ranging from daily to weekly to 3-weekly. Dose-limiting toxicites included neuropathy and neutropenia. Responses were seen in a variety of tumor types. Phase II studies verified activity in taxane-refractory metastatic breast cancer. The FDA has approved ixabepilone for use as monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer. Ixabepilone is an efficacious option for patients with refractory metastatic breast cancer. The safety profile is similar to that of taxanes, with neuropathy and neutropenia being dose-limiting. Studies are ongoing with the use of both iv and oral formulations and in combination with other chemotherapeutic and biologic agents. PMID:19707381

  6. The Burkholderia pseudomallei Enoyl-Acyl Carrier Protein Reductase FabI1 Is Essential for In Vivo Growth and Is the Target of a Novel Chemotherapeutic with Efficacy

    PubMed Central

    Cummings, Jason E.; Kingry, Luke C.; Rholl, Drew A.; Schweizer, Herbert P.

    2014-01-01

    The bacterial fatty acid biosynthesis pathway is a validated target for the development of novel chemotherapeutics. However, since Burkholderia pseudomallei carries genes that encode both FabI and FabV enoyl-acyl carrier protein (ACP) reductase homologues, the enoyl-ACP reductase that is essential for in vivo growth needs to be defined so that the correct drug target can be chosen for development. Accordingly, ΔfabI1, ΔfabI2, and ΔfabV knockout strains were constructed and tested in a mouse model of infection. Mice infected with a ΔfabI1 strain did not show signs of morbidity, mortality, or dissemination after 30 days of infection compared to the wild-type and ΔfabI2 and ΔfabV mutant strains that had times to mortality of 60 to 84 h. Although signs of morbidity and mortality of ΔfabI2 and ΔfabV strains were not significantly different from those of the wild-type strain, a slight delay was observed. A FabI1-specific inhibitor was used to confirm that inhibition of FabI1 results in reduced bacterial burden and efficacy in an acute B. pseudomallei murine model of infection. This work establishes that FabI1 is required for growth of Burkholderia pseudomallei in vivo and is a potential molecular target for drug development. PMID:24277048

  7. Medication Treatment Efficacy and Chronic Orofacial Pain.

    PubMed

    Clark, Glenn T; Padilla, Mariela; Dionne, Raymond

    2016-08-01

    Chronic pain in the orofacial region has always been a vexing problem for dentists to diagnose and treat effectively. For trigeminal neuropathic pain, there are 3 medications (gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors) to use plus topical anesthetics that have therapeutic efficacy. For chronic daily headaches (often migraine in origin), 3 prophylactic medications have reasonable therapeutic efficacy (β-blockers, tricyclic antidepressants, and antiepileptic drugs). The 3 Food and Drug Administration-approved drugs for fibromyalgia (pregabalin, duloxetine, and milnacipran) are not robust, with poor efficacy. For osteroarthritis, nonsteroidal anti-inflammatory drugs have therapeutic efficacy and when gastritis contraindicates them, corticosteriod injections are helpful. PMID:27475515

  8. Spectroscopic detection of chemotherapeutics and antioxidants

    NASA Astrophysics Data System (ADS)

    Latka, Ines; Grüner, Roman; Matthäus, Christian; Dietzek, Benjamin; Werncke, W.; Lademann, Jürgen; Popp, Jürgen

    2012-06-01

    The hand-foot-syndrome presents a severe dermal side-effect of chemotherapeutic cancer treatment. The cause of this side-effect is the elimination of systemically administered chemotherapeutics with the sweat. Transported to the skin surface, the drugs subsequently penetrate into the skin in the manner of topically applied substances. Upon accumulation of the chemotherapeutics in the skin the drugs destroy cells and tissue - in the same way as they are supposed to act in cancer cells. Aiming at the development of strategies to illuminate the molecular mechanism underlying the handfoot- syndrome (and, in a second step, strategies to prevent this severe side-effect), it might be important to evaluate the concentration and distribution of chemotherapeutics and antioxidants in the human skin. The latter can be estimated by the carotenoid concentration, as carotenoids serve as marker substances for the dermal antioxidative status.Following the objectives outlined above, this contribution presents a spectroscopic study aiming at the detection and quantification of carotenoids and selected chemotherapeutics in human skin. To this end, spontaneous Raman scattering and coherent anti-Stokes Raman scattering (CARS) microspectroscopy are combined with two-photon excited fluorescence. While the latter technique is Please verify that (1) all pages are present, (2) all figures are correct, (3) all fonts and special characters are correct, and (4) all text and figures fit within the red margin lines shown on this review document. Complete formatting information is available at http://SPIE.org/manuscripts Return to your MySPIE To Do List at http://myspie.org and approve or disapprove this submission. Your manuscript will not be published without this approval.restricted to the detection of fluorescent chemotherapeutics, e.g., doxorubicin, the vibrational spectroscopic techniques can - in principle - be applied to any type of analyte molecules. Furthermore, we will present the

  9. Fabrication of water-soluble polymer-encapsulated As4S4 to increase oral bioavailability and chemotherapeutic efficacy in AML mice

    PubMed Central

    Ma, Qiang; Wang, Chuan; Li, Xiaojin; Guo, Hua; Meng, Jie; Liu, Jian; Xu, Haiyan

    2016-01-01

    Realgar (As4S4) has been demonstrated to be effective for the treatment of acute myeloid leukemia (AML); it has the advantages of no drug resistance and oral administration. Nevertheless, its poor solubility has been an obstacle to its bioavailability, requiring high-dose administration over a long period. We investigated whether crushing realgar crystals to the nanoscale and encapsulating the particles in a water-soluble polymer in one step using hot-melt extrusion would increase the bioavailability of As4S4. Raw As4S4 (r-As4S4) and water-soluble polymer were processed via co-rotating twin screw extrusion. The resulting product (e-As4S4) was characterized by SEM, XRD, and DLS. The cytotoxicity and therapeutic effects of e-As4S4 were evaluated in vivo and in vitro. The results show that e-As4S4 dissolved rapidly in water, forming a stable colloid solution. The average size of e-As4S4 particles was 680 nm, which was reduced by more than 40-fold compared with that of r-As4S4. The bioavailability of e-As4S4 was up to 12.6-fold higher than that of r-As4S4, and it inhibited the proliferation of HL-60 cells much more effectively than did r-As4S4, inducing apoptosis and significantly reducing the infiltration of HL-60 cells into the bone marrow, spleen, and liver. This in turn prolonged the survival of AML mice. PMID:27383126

  10. Inhibition of Lysyl Oxidases Improves Drug Diffusion and Increases Efficacy of Cytotoxic Treatment in 3D Tumor Models

    PubMed Central

    Schütze, Friedrich; Röhrig, Florian; Vorlová, Sandra; Gätzner, Sabine; Kuhn, Anja; Ergün, Süleyman; Henke, Erik

    2015-01-01

    Tumors are characterized by a rigid, highly cross-linked extracellular matrix (ECM), which impedes homogeneous drug distribution and potentially protects malignant cells from exposure to therapeutics. Lysyl oxidases are major contributors to tissue stiffness and the elevated expression of these enzymes observed in most cancers might influence drug distribution and efficacy. We examined the effect of lysyl oxidases on drug distribution and efficacy in 3D in vitro assay systems. In our experiments elevated lysyl oxidase activity was responsible for reduced drug diffusion under hypoxic conditions and consequently impaired cytotoxicity of various chemotherapeutics. This effect was only observed in 3D settings but not in 2D-cell culture, confirming that lysyl oxidases affect drug efficacy by modification of the ECM and do not confer a direct desensitizing effect. Both drug diffusion and efficacy were strongly enhanced by inhibition of lysyl oxidases. The results from the in vitro experiments correlated with tumor drug distribution in vivo, and predicted response to therapeutics in murine tumor models. Our results demonstrate that lysyl oxidase activity modulates the physical barrier function of ECM for small molecule drugs influencing their therapeutic efficacy. Targeting this process has the potential to significantly enhance therapeutic efficacy in the treatment of malignant diseases. PMID:26620400

  11. Evolving Evidence of the Efficacy and Safety of nab-Paclitaxel in the Treatment of Cancers with Squamous Histologies

    PubMed Central

    Loong, Herbert H.; Chan, Alvita C.Y.; Wong, Ashley C.Y.

    2016-01-01

    Taxanes, such as paclitaxel and docetaxel, are well-established cytotoxic chemotherapeutics used in the treatment of a variety of cancers, including those of squamous histology. In their formulation, both agents require solvents, which have been associated with hypersensitivity reactions, peripheral neuropathy, hepatic toxicities, and impaired drug delivery. nab-Paclitaxel is a novel, albumin-bound form of paclitaxel with improved tolerability, bioavailability, and efficacy compared with solvent-based paclitaxel. Currently, nab-paclitaxel is approved for the treatment of metastatic breast cancer, locally advanced/metastatic non-small cell lung cancer (NSCLC), and metastatic pancreatic cancer. Clinical studies suggest that nab-paclitaxel may be particularly effective in cancers with squamous histology, including NSCLC. This article reviews the emerging evidence supporting nab-paclitaxel as an effective agent in the treatment of malignancies of squamous histology. PMID:26918039

  12. Identifying Efficacious Treatment Components of Panic Control Treatment for Adolescents: A Preliminary Examination

    ERIC Educational Resources Information Center

    Micco, Jamie A.; Choate-Summers, Molly L.; Ehrenreich, Jill T.; Pincus, Donna B.; Mattis, Sara G.

    2007-01-01

    Panic Control Treatment for Adolescents (PCT-A) is a developmentally sensitive and efficacious treatment for adolescents with panic disorder. The present study is a preliminary examination of the relative efficacy of individual treatment components in PCT-A in a sample of treatment completers; the study identified when rapid improvements in panic…

  13. The Role of Transporters in the Toxicity of Chemotherapeutic Drugs: Focus on Transporters for Organic Cations.

    PubMed

    Hucke, Anna; Ciarimboli, Giuliano

    2016-07-01

    The introduction of chemotherapy in the treatment of cancer is one of the most important achievements of modern medicine, even allowing the cure of some lethal diseases such as testicular cancer and other malignant neoplasms. The number and type of chemotherapeutic agents available have steadily increased and have developed until the introduction of targeted tumor therapy. It is now evident that transporters play an important role for determining toxicity of chemotherapeutic drugs not only against target but also against nontarget cells. This is of special importance for intracellularly active hydrophilic drugs, which cannot freely penetrate the plasma membrane. Because many important chemotherapeutic agents are substrates of transporters for organic cations, this review discusses the known interaction of these substances with these transporters. A particular focus is given to the role of transporters for organic cations in the development of side effects of chemotherapy with platinum derivatives and in the efficacy of recently developed tyrosine kinase inhibitors to specifically target cancer cells. It is evident that specific inhibition of uptake transporters may be a possible strategy to protect against undesired side effects of platinum derivatives without compromising their antitumor efficacy. These transporters are also important for efficient targeting of tyrosine kinase inhibitors to cancer cells. However, in order to achieve the aims of protecting from undesired toxicities and improving the specificity of uptake by tumor cells, an exact knowledge of transporter expression, function, regulation under normal and pathologic conditions, and of genetically and epigenetically regulation is mandatory. PMID:27385173

  14. The Role of Transporters in the Toxicity of Chemotherapeutic Drugs: Focus on Transporters for Organic Cations.

    PubMed

    Hucke, Anna; Ciarimboli, Giuliano

    2016-07-01

    The introduction of chemotherapy in the treatment of cancer is one of the most important achievements of modern medicine, even allowing the cure of some lethal diseases such as testicular cancer and other malignant neoplasms. The number and type of chemotherapeutic agents available have steadily increased and have developed until the introduction of targeted tumor therapy. It is now evident that transporters play an important role for determining toxicity of chemotherapeutic drugs not only against target but also against nontarget cells. This is of special importance for intracellularly active hydrophilic drugs, which cannot freely penetrate the plasma membrane. Because many important chemotherapeutic agents are substrates of transporters for organic cations, this review discusses the known interaction of these substances with these transporters. A particular focus is given to the role of transporters for organic cations in the development of side effects of chemotherapy with platinum derivatives and in the efficacy of recently developed tyrosine kinase inhibitors to specifically target cancer cells. It is evident that specific inhibition of uptake transporters may be a possible strategy to protect against undesired side effects of platinum derivatives without compromising their antitumor efficacy. These transporters are also important for efficient targeting of tyrosine kinase inhibitors to cancer cells. However, in order to achieve the aims of protecting from undesired toxicities and improving the specificity of uptake by tumor cells, an exact knowledge of transporter expression, function, regulation under normal and pathologic conditions, and of genetically and epigenetically regulation is mandatory.

  15. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    ERIC Educational Resources Information Center

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  16. Conventional and Unconventional Treatments for Stress among Methadone-Maintained Patients: Treatment Willingness and Perceived Efficacy

    PubMed Central

    Barry, Declan T.; Beitel, Mark; Breuer, Timothy; Cutter, Christopher J.; Savant, Jonathan; Schottenfeld, Richard S.; Rounsaville, Bruce J.

    2010-01-01

    We surveyed 150 methadone maintenance treatment (MMT) program patients about willingness to use, and perceived efficacy of, conventional and unconventional nonpharmacological stress-related treatments. Although levels of treatment willingness and perceived efficacy for both conventional and unconventional treatments were high, ratings for conventional interventions were, on average, significantly higher than those for unconventional ones. Dimensions of psychiatric distress—but not demographic or MMT characteristics—predicted treatment willingness for conventional therapies and treatment willingness and perceived efficacy for unconventional therapies. These findings are likely to have implications for resource and program planning in MMT programs. PMID:21314756

  17. Efficacy of newer generation antipsychotics in the treatment of schizophrenia.

    PubMed

    Tandon, R; Jibson, M D

    2003-01-01

    The advent of the newer 'atypical' antipsychotic medications has revolutionized the pharmacologic treatment of schizophrenia and other psychotic disorders. In contrast to the older conventional antipsychotic agents, atypical medications have a broader spectrum of efficacy (greater efficacy in negative, cognitive, and mood symptoms) and a lower risk of extrapyramidal symptoms (EPS) and tardive dyskinesia. Due to concerns surrounding hematological safety and other adverse effects, clozapine is used principally in patients refractory to treatment with other antipsychotic agents. The other three universally available atypical agents (risperidone, olanzapine, and quetiapine) collectively constitute about 70% of all antipsychotic prescriptions in the USA. Despite the broad popularity of these medications and their rapid adoption in general clinical practice, there are limited data on how they compare to each other with regards to their overall efficacy and also as to their efficacy in specific symptom domains. To address this question, two separate analyses were undertaken. First, all published, short-term, randomized, controlled clinical trials of these agents in schizophrenia and schizoaffective disorder were reviewed and the extent of improvement across these agents was compared. While the amount of improvement with a particular agent across its different studies varied, the average improvement was similar for the agents for all efficacy parameters considered. Secondly, all randomized, controlled clinical trials directly comparing two or more of these agents in patients with schizophrenia or schizoaffective disorder were analyzed. Only three such trials (all industry sponsored) were identified; while there were differences in methodology and small differences in efficacy on a minority of measures on which comparisons were undertaken, the preponderance of data suggested no differences in efficacy. While data thus far do not support assertions of differential efficacy

  18. BMX Negatively Regulates BAK Function, Thereby Increasing Apoptotic Resistance to Chemotherapeutic Drugs.

    PubMed

    Fox, Joanna L; Storey, Alan

    2015-04-01

    The ability of chemotherapeutic agents to induce apoptosis, predominantly via the mitochondrial (intrinsic) apoptotic pathway, is thought to be a major determinant of the sensitivity of a given cancer to treatment. Intrinsic apoptosis, regulated by the BCL2 family, integrates diverse apoptotic signals to determine cell death commitment and then activates the nodal effector protein BAK to initiate the apoptotic cascade. In this study, we identified the tyrosine kinase BMX as a direct negative regulator of BAK function. BMX associates with BAK in viable cells and is the first kinase to phosphorylate the key tyrosine residue needed to maintain BAK in an inactive conformation. Importantly, elevated BMX expression prevents BAK activation in tumor cells treated with chemotherapeutic agents and is associated with increased resistance to apoptosis and decreased patient survival. Accordingly, BMX expression was elevated in prostate, breast, and colon cancers compared with normal tissue, including in aggressive triple-negative breast cancers where BMX overexpression may be a novel biomarker. Furthermore, BMX silencing potentiated BAK activation, rendering tumor cells hypersensitive to otherwise sublethal doses of clinically relevant chemotherapeutic agents. Our finding that BMX directly inhibits a core component of the intrinsic apoptosis machinery opens opportunities to improve the efficacy of existing chemotherapy by potentiating BAK-driven cell death in cancer cells. PMID:25649765

  19. Efficacy of an Emotion-Focused Treatment for Prolonged Fatigue

    ERIC Educational Resources Information Center

    Schutte, Nicola S.; Malouff, John M.; Brown, Rhonda F.

    2008-01-01

    Previous research findings have suggested a relationship between less adaptive emotional functioning and fatigue. The present study used a research design involving multiple baselines across participants to evaluate the efficacy of a new emotion-focused treatment for prolonged fatigue delivered in a cognitive behavioral therapy framework. The 13…

  20. Reviewing efficacy of alternative water treatment techniques.

    PubMed

    Hambidge, A

    2001-06-01

    synergistic effect in the inactivation of coliphage MS-2 and poliovirus. Other techniques: There are a number of other techniques. We have conducted trials of most of these in the control of Legionella sp., but these fall out of the scope of this article, and as such less emphasis has been placed on them here. Ozonation: Ozone [O3] is an oxidising gas, generated electrically from oxygen [O2]. L. pneumophila can be killed at < 1 mg/L of ozone [Edelstien et al 1982]. Muraca et al [1987] found that 1-2 mg/L of continuous ozone over a six hour contact time, produced a 5 logarithm decrease of L. pneumophila. The effectiveness of ozone treatment against a range of bacteria and coliphages has been studied Botzenhart et al [1993]. E. coli was least resistant to ozone, followed by MS 2-coliphage and PhiX 174-coliphage, with L. pneumophila and Bacillus subtilis spores being the most resistant. (ABSTRACT TRUNCATED)

  1. Evaluation of treatment efficacy in sleep apnea hypopnea syndrome.

    PubMed

    Sériès, F

    1996-11-01

    The evaluation of treatment efficacy consists in evaluating their efficacy to normalize sleep-related breathing disorders and neuropsychological consequences and witness complaints, patients' compliance, and the risk or side effects to benefits ratio. Polysomnographic studies are the gold standard for assessing the effects of treatments on nocturnal breathing the sleep characteristics, but the timing of control sleep studies must take into account the possible changes in treatment efficacy with time. Determining the effective positive pressure level during split nights or with a multifactorial regression model may be helpful but can result in an underestimation of the pressure setting. The utility of unassisted home sleep recordings during CPAP therapy is limited by the number of signals recorded and the absence of sleep recording. The evaluation of neuropsychological improvements has to be multifactorial to evaluate the subjective and objective effects of SAHS treatments. The compliance to CPAP therapy must be evaluated by pressure counter or time counter measurements rather than on the reported use. CPAP observance can be reliably estimated after the first month of therapy is linked to improvement in diurnal symptoms. As for any disease, SAHS treatment must be adapted to the individual characteristics of the patient and of his or her disease. Therefore, the choice between weight loss, pharyngeal or maxillomandibular surgery, anterior mandibular positioners or tongue retaining devices, nasal CPAP, BiPAP, and tracheostomy depends on the patient's complaints and morbidity risk factors and on the respective side effects to benefits ratio of these therapeutic procedures.

  2. Suppression of PRKAR1A expression enhances anti-proliferative and apoptotic effects of protein kinase inhibitors and chemotherapeutic drugs on cholangiocarcinoma cells.

    PubMed

    Loilome, Watcharin; Juntana, Sirinun; Pinitsoontorn, Chadamas; Namwat, Nisana; Tassaneeyakul, Wichittra; Yongvanit, Puangrat

    2012-01-01

    Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. In the present study, we aimed to determine synergistic and/or additive effects of chemotherapeutic agents, including protein kinase inhibitors (i.e. sorafenib, sunitinib, gefitinib, Met inhibitor) and conventional chemotherapeutic drugs (i.e. 5-fluorouracil, doxorubicin, paclitaxel, gemcitabine), in PRKARIA knockdown CCA cell lines. The results revealed that PRKAR1A suppressed CCA cell lines demonstrated enhanced sensitivity to some chemotherapeutic drugs when compared to control cells. Moreover, PRKAR1A knockdown in combination with either sorafenib or 5-fluorouracil increased apoptotic effects on CCA cell lines. Therefore, selective inhibition of PRKAR1A appears to enhance the growth inhibitory effects of chemotherapeutic drugs as well as induce apoptotic cell death. Our findings suggest that additional suppression of PRKAR1A expression may increase the efficacy of conventional CCA chemotherapeutic treatment. Clinical studies in CCA patients now need to be conducted. PMID:23480756

  3. Synergistic activities of a silver(I) glutamic acid complex and reactive oxygen species (ROS): a novel antimicrobial and chemotherapeutic agent.

    PubMed

    Batarseh, K I; Smith, M A

    2012-01-01

    The antimicrobial and chemotherapeutic activities of a silver(I) glutamic acid complex with the synergistic concomitant generation of reactive oxygen species (ROS) were investigated here. The ROS generation system employed was via Fenton chemistry. The antimicrobial and chemotherapeutic activities were investigated on Staphylococcus aureus ATCC 43300 and Escherichia coli bacteria, and Vero and MCF-7 tumor cell lines, respectively. Antimicrobial activities were conducted by determining minimum inhibitory concentration (MIC), while chemotherapeutic efficacies were done by serial dilution using standard techniques to determine the half maximal inhibitory concentration (IC50). The antimicrobial and chemotherapeutic results obtained were compared with positive control drugs gentamicin, oxacillin, penicillin, streptomycin and cisplatin, a ubiquitously used platinum-based antitumor drug, and with the silver(I) glutamic acid complex and hydrogen peroxide separately. Based on MIC and IC50 values, it was determined that this synergistic approach was very effective at extremely low concentrations, especially when compared with the other drugs evaluated here. This finding might be of great significance regarding metronomic dosing when this synergistic approach is clinically implemented. Since silver at low concentrations exhibits no toxic, mutagenic and carcinogenic activities, this might offer an alternative approach for the development of safer silver-based antimicrobial and chemotherapeutic drugs, thereby reducing or even eliminating the toxicity associated with current drugs. Accordingly, the present approach might be integrated into the systemic clinical treatment of infectious diseases and cancer. PMID:22680634

  4. Antibody–drug conjugates as novel anti-cancer chemotherapeutics

    PubMed Central

    Peters, Christina; Brown, Stuart

    2015-01-01

    Over the past couple of decades, antibody–drug conjugates (ADCs) have revolutionized the field of cancer chemotherapy. Unlike conventional treatments that damage healthy tissues upon dose escalation, ADCs utilize monoclonal antibodies (mAbs) to specifically bind tumour-associated target antigens and deliver a highly potent cytotoxic agent. The synergistic combination of mAbs conjugated to small-molecule chemotherapeutics, via a stable linker, has given rise to an extremely efficacious class of anti-cancer drugs with an already large and rapidly growing clinical pipeline. The primary objective of this paper is to review current knowledge and latest developments in the field of ADCs. Upon intravenous administration, ADCs bind to their target antigens and are internalized through receptor-mediated endocytosis. This facilitates the subsequent release of the cytotoxin, which eventually leads to apoptotic cell death of the cancer cell. The three components of ADCs (mAb, linker and cytotoxin) affect the efficacy and toxicity of the conjugate. Optimizing each one, while enhancing the functionality of the ADC as a whole, has been one of the major considerations of ADC design and development. In addition to these, the choice of clinically relevant targets and the position and number of linkages have also been the key determinants of ADC efficacy. The only marketed ADCs, brentuximab vedotin and trastuzumab emtansine (T-DM1), have demonstrated their use against both haematological and solid malignancies respectively. The success of future ADCs relies on improving target selection, increasing cytotoxin potency, developing innovative linkers and overcoming drug resistance. As more research is conducted to tackle these issues, ADCs are likely to become part of the future of targeted cancer therapeutics. PMID:26182432

  5. AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy.

    PubMed

    Wei, Xi; Duan, Wei; Li, Ying; Zhang, Sheng; Xin, Xiaojie; Sun, Lei; Gao, Ming; Li, Qing; Wang, Dong

    2016-06-01

    Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer.

  6. AT101 exerts a synergetic efficacy in gastric cancer patients with 5-FU based treatment through promoting apoptosis and autophagy

    PubMed Central

    Wei, Xi; Duan, Wei; Li, Ying; Zhang, Sheng; Xin, Xiaojie; Sun, Lei; Gao, Ming; Li, Qing; Wang, Dong

    2016-01-01

    Gastric cancer remains a disease with a high mortality rate despite of multiple therapeutic strategies. So far, it is very important to develop new treatment approaches to improve current therapeutic efficacy in gastric cancer. Apurinic/apyrimidinic endonuclease (APE1) involves in DNA base excision repair (BER) during DNA damage pathway. APE1 was found to be associated with poor overall survival with gastric cancer patients. In the in vitro experiment, we tested APE1 inhibitor-AT101 could potently inhibit gastric cancer cell growth and further induce cancer cell apoptosis and autophagy through p53-dependent pathway. Downregulation of APE1 by AT101 has ability to suppress gastric cancer cell migration and renewal through inhibition of CD133, Nanog and LC3expression. Based on findings that Her-2 positive expression cases has poor prognosis from our dataset and TCGA database, we investigated the role of AT101 in synergetic efficacy with 5-FU treatment in Her-2 overexpression gastric cancer in vivo, indicating that AT101 is able to enhance 5-FU in the shrinkage of xenograft mice tumor and induction of cell apoptosis. In summary, the data obtained from our study showed APE1 is guided as a potential therapeutic target for gastric cancer. AT101 could be regarded as a potent inhibitor to promote chemotherapeutic sensitivity in patients with gastric cancer. PMID:27144437

  7. Treatment efficacy of algae-based sewage treatment plants.

    PubMed

    Mahapatra, Durga Madhab; Chanakya, H N; Ramachandra, T V

    2013-09-01

    Lagoons have been traditionally used in India for decentralized treatment of domestic sewage. These are cost effective as they depend mainly on natural processes without any external energy inputs. This study focuses on the treatment efficiency of algae-based sewage treatment plant (STP) of 67.65 million liters per day (MLD) capacity considering the characteristics of domestic wastewater (sewage) and functioning of the treatment plant, while attempting to understand the role of algae in the treatment. STP performance was assessed by diurnal as well as periodic investigations of key water quality parameters and algal biota. STP with a residence time of 14.3 days perform moderately, which is evident from the removal of total chemical oxygen demand (COD) (60 %), filterable COD (50 %), total biochemical oxygen demand (BOD) (82 %), and filterable BOD (70 %) as sewage travels from the inlet to the outlet. Furthermore, nitrogen content showed sharp variations with total Kjeldahl nitrogen (TKN) removal of 36 %; ammonium N (NH4-N) removal efficiency of 18 %, nitrate (NO3-N) removal efficiency of 22 %, and nitrite (NO2-N) removal efficiency of 57.8 %. The predominant algae are euglenoides (in facultative lagoons) and chlorophycean members (maturation ponds). The drastic decrease of particulates and suspended matter highlights heterotrophy of euglenoides in removing particulates.

  8. Using LASSO Regression to Predict Rheumatoid Arthritis Treatment Efficacy

    PubMed Central

    Odgers, David J.; Tellis, Natalie; Hall, Heather; Dumontier, Michel

    2016-01-01

    Rheumatoid arthritis (RA) accounts for one-fifth of the deaths due to arthritis, the leading cause of disability in the United States. Finding effective treatments for managing arthritis symptoms are a major challenge, since the mechanisms of autoimmune disorders are not fully understood and disease presentation differs for each patient. The American College of Rheumatology clinical guidelines for treatment consider the severity of the disease when deciding treatment, but do not include any prediction of drug efficacy. Using Electronic Health Records and Biomedical Linked Open Data (LOD), we demonstrate a method to classify patient outcomes using LASSO penalized regression. We show how Linked Data improves prediction and provides insight into how drug treatment regimes have different treatment outcome. Applying classifiers like this to decision support in clinical applications could decrease time to successful disease management, lessening a physical and financial burden on patients individually and the healthcare system as a whole. PMID:27570666

  9. Using LASSO Regression to Predict Rheumatoid Arthritis Treatment Efficacy.

    PubMed

    Odgers, David J; Tellis, Natalie; Hall, Heather; Dumontier, Michel

    2016-01-01

    Rheumatoid arthritis (RA) accounts for one-fifth of the deaths due to arthritis, the leading cause of disability in the United States. Finding effective treatments for managing arthritis symptoms are a major challenge, since the mechanisms of autoimmune disorders are not fully understood and disease presentation differs for each patient. The American College of Rheumatology clinical guidelines for treatment consider the severity of the disease when deciding treatment, but do not include any prediction of drug efficacy. Using Electronic Health Records and Biomedical Linked Open Data (LOD), we demonstrate a method to classify patient outcomes using LASSO penalized regression. We show how Linked Data improves prediction and provides insight into how drug treatment regimes have different treatment outcome. Applying classifiers like this to decision support in clinical applications could decrease time to successful disease management, lessening a physical and financial burden on patients individually and the healthcare system as a whole. PMID:27570666

  10. Efficacy of extended cefquinome treatment of clinical Staphylococcus aureus mastitis.

    PubMed

    Swinkels, J M; Cox, P; Schukken, Y H; Lam, T J G M

    2013-08-01

    Clinical Staphylococcus aureus mastitis is difficult to cure. Extended antimicrobial treatment is often advocated as a practical approach to improve cure rates; however, scientific evidence of this hypothesis is lacking. A multi-centered, nonblinded, randomized, positive-controlled clinical trial was conducted in 5 European countries-France, Hungary, Italy, the Netherlands, and the United Kingdom-to study the efficacy of an extended intramammary cefquinome treatment (5 d) compared with a standard intramammary cefquinome treatment (1.5 d) of Staph. aureus clinical mastitis. Least squares means estimates of bacteriological cure during lactation were 34% [standard error (SE)=9.9%] for the standard treatment group and 27% (SE=8.4%) for the extended treatment group. In the final model, extended therapy was not significantly better. The only factor predicting bacteriological cure was pretreatment cow somatic cell count (SCC). Cows with >250,000 cells/mL in milk before treatment were less likely to cure. Least squares means of clinical cure during lactation was 60% (SE=19%) for the standard treatment group and 82% (SE=12%) for the extended treatment group. In the final model, clinical cure after extended treatment was significantly better. Pretreatment cow udder firmness predicted clinical cure. Firm udders were less likely to cure clinically. Irrespective of treatment regimen, new infection rates with pathogens other than Staph. aureus were higher (42%) after bacteriological cure than after nonbacteriological cure (22%) and cured cows had a significantly lower SCC. In conclusion, independent of the treatment protocol, cows with an SCC <250,000 cells/mL before treatment showed a higher probability of bacteriological cure. It appears that successful treatment of clinical Staph. aureus mastitis with cefquinome is associated with an increased number of new infections with coagulase-negative staphylococci. Extended treatment improved clinical, but not bacteriological, cure

  11. Treatment efficacy of intramuscular promethazine for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey R.; Jennings, Richard T.; Beck, Bradley G.; Bagian, James P.

    1993-01-01

    Intramuscular promethazine and its efficacy in the treatment of Space Motion Sickness (SMS) were evaluated using standardized questions administered during postflight debriefings to crewmembers immediately after their first Shuttle flight. The comparison showed that 25 percent of crewmembers treated with IM promethazine were 'sick' on flight day 2, compared to 50 percent of crewmembers who did not receive promethazine, 90 percent reported immediate symptom relief as well. Untreated crewmembers typically have slow symptom resolution over 72-96 h, and those treated with oral scopolamine/dextroamphetamine show delayed symptom development. This study suggests that intramuscular promethazine is an effective treatment for SMS and merits continued use and further controlled investigations.

  12. Apoptosis of human tumor cells by chemotherapeutic anthracyclines is enhanced by Bax overexpression.

    PubMed

    Lu, Y; Yagi, T

    1999-09-01

    One of the major factors for efficacy of a chemotherapeutic drug is its activity to induce apoptosis of tumor cells. Doxorubicin and daunorubicin, radiomimetic anthracycline-group drugs, have been used for chemotherapy for about 30 years. Here we established the colorectal tumor and osteosarcoma cells in which Bax expression can be induced by the treatment of isopropyl-beta-D-thiogalactopyranoside, and examined the effect of the Bax overexpression on the cell death caused by these drugs. While the Bax overexpression neither affected growth nor morphology of the undamaged cells, it enhanced the cell death caused by these drugs. Increase in cellular nucleus fragmentation and DNA ladder formation indicates that the Bax-enhanced cell death is due to enhanced apoptosis of the drug-treated cells. The enhanced cell death was not observed when the cells were irradiated with X-ray or treated with other chemotherapeutic agents we examined. These results indicate that Bax may have a specific role to enhance the efficacy of chemotherapy with anthracycline-group agents.

  13. Follow up of patients who start treatment with antidepressants: treatment satisfaction, treatment compliance, efficacy and safety

    PubMed Central

    2013-01-01

    Background Measuring satisfaction with treatment has proved useful to ascertain the treatment features that are most important to the patients, and to explain increased treatment compliance. However, there are few studies that relate satisfaction to other clinical or self-perceived health status indicators. Recent studies have shown the close relationship between satisfaction with treatment, treatment compliance, and effectiveness. This study attempts to design and validate a scale to evaluate satisfaction with antidepressant drug therapy, assess treatment compliance (self-reported, validated questionnaire, drug accountability and electronic monitorization system), assess efficacy in reducing depressive symptoms and safety in patients who initiate antidepressant drug therapy, as well as to establish predictors of satisfaction, compliance and effectiveness with these drugs. Methods/design This is an observational longitudinal study with a cohort of adults initiating treatment with antidepressant drugs. A multi-centre study will be performed in which 20 Primary Care practices from Castilla-La Mancha are expected to participate. An initial interview and follow-up visits at 15 days, 1, 3, 6, 9 and 12 months will be conducted with all study participants. 706 subjects will be studied (95% confidence interval, precision ± 3%, expected rate of non-compliance 50%, expected non-responders and lost to follow up rate 15%). The following measurements will be performed: development and validation of a scale of satisfaction with antidepressant therapy, participant and antidepressant characteristics, treatment compliance evaluation (Haynes-Sackett Test, Morisky-Green Test, drug accountability and Medication Event Monitoring System), depression symptom reduction (Hamilton Depression Rating Scale and Montgomery-Asberg Depression Rating Scale), observation of adverse effects, and beliefs about treatment (The Beliefs about Medicines Questionnaire). Discussion Antidepressant drugs are

  14. Efficacy of myrrh in the treatment of human Schistosomiasis mansoni.

    PubMed

    Barakat, Rashida; Elmorshedy, Hala; Fenwick, Alan

    2005-08-01

    Myrrh (Mirazid) has been produced and marketed as an antischistosomal drug since 2001. The current study was designed to assess the efficacy of a commercially available product of myrrh. One hundred four individuals, infected with Schistosoma mansoni, were randomized in two groups, one for myrrh and the second for praziquantel. Treatment-whether myrrh or praziquantel-was given twice with a 3-week interval. The cure rate with myrrh was very low, 15.6% after the first treatment, and 8.9% after the second treatment. Egg reduction among uncured persons was also very low, being 17.2% after the first treatment, and 28% after the second treatment. Praziquantel cure rate was 73.7% and 76.3%, and individuals still passing S. mansoni ova after praziquantel treatment showed a substantial reduction in the geometric mean egg counts (84% and 88.2% after the first and second treatments, respectively). When 34 individuals-uncured after two myrrh treatments-were offered praziquantel in the standard dose, 32 of them stopped passing S. mansoni eggs when tested 4 weeks post-treatment. The results of the current study raise serious doubts about the antischistosomal properties of Mirazid. PMID:16103605

  15. Nanostructured Lipid Carriers: A Novel Platform for Chemotherapeutics.

    PubMed

    Rizwanullah, Md; Ahmad, Javed; Amin, Saima

    2016-01-01

    Cancer is a disease manifested as abnormal cells division without control. If it is not detected and cured very timely, it can invade other healthy tissues resulting in metastasis. Chemotherapy is the first line treatment for cancer, but due to lack of specificity of most of the anticancer drugs, is associated with side effects that affect the quality of life. Nanostructured lipid carriers (NLC) are one of the promising nano-carriers for the development of effective targeted therapies for cancer chemotherapeutics. These bio-compatible and/or bio-degradable lipids based nanoparticles are composed of solid and liquid lipids as a core matrix dispersed in surfactant solution. NLC improve the aqueous solubility of most of the hydrophobic cancer therapeutics. Their surface modification can be used for overcoming drug resistance in cancer chemotherapy, to achieve site specific targeting for better efficacy and reduced dose related toxicity. The present review is an attempt to contemplate their pharmaceutical, biopharmaceutical aspects and application in cell targeting, gene delivery and in theranostics. PMID:26279117

  16. Tunable release of chemotherapeutic and vascular disrupting agents from injectable fiber fragments potentiates combination chemotherapy.

    PubMed

    Luo, Xiaoming; Xu, Guisen; Wei, Jiaojun; Chen, Maohua; Zhang, Hong; Li, Xiaohong

    2016-06-15

    Cancer progression and metastasis relies much on vasculature networks in tumor microenvironment, and the combination treatment with chemotherapeutic drugs and vascular disrupting agents represents apparent clinical benefits. In the current study, fiber fragments with loadings of hydroxycamptothecin (HCPT) or combretastatin A-4 (CA4) were proposed for tumor inhibition and blood vessel disruption after local administration in tumors. To address challenges in balancing the disruption of tumor vessels and intratumoral uptake of chemotherapeutic agents, this study is focus on release tuning of HCPT and CA4 from the fiber fragment mixtures. Hydroxypropyl-β-cyclodextrin (HPCD) was blended at ratios from 0 to 10% into CA4-loaded fiber fragments (Fc) to modulate CA4 release durations from 0.5 to 24days, and HCPT-loaded fiber fragments (Fh) indicated a sustained release for over 35days. In vitro cytotoxicity tests indicated a sequential inhibition on the endothelial and tumor cell growth, and the growth inhibition of tumor cells was more significant after treatment with mixtures of Fh and Fc containing 2% HPCD (Fc2) than that of other mixtures. In an orthotopic breast tumor model, compared with those of free CA4, or Fc with a fast or slow release of CA4, Fh/Fc mixtures with CA4 release durations from 2 to 12days indicated a lower tumor growth rate, a prolonged animal survival, a lower vessel density in tumors, and a less significant tumor metastasis. In addition, the tumor cell proliferation rate, hypoxia-inducible factor-1α expression within tumors, and the number of surface metastatic nodules in lungs were significantly lower after treatment with Fh/Fc2 mixtures with a CA4 release duration of 5days than those of other mixtures. It demonstrates the advantages of fiber fragment mixtures in independently modulating the release of multiple drugs and the essential role of release tuning of chemotherapeutic drugs and vascular disrupting agents in improving the therapeutic

  17. Clinical efficacy of Yingliu treatment for Graves disease

    PubMed Central

    Yang, Hua; Bi, Xiaojuan; Tang, Hong; Zeng, Juanhua; Cong, Yilei; Wu, Tengfei; Chen, Qiuye

    2015-01-01

    Objective: To observe the clinical efficacy and safety of the traditional Chinese medicine (TCM) mixture Yingliu combined with methimazole medication for the treatment of Graves disease (GD). Method: In a randomized, paralleled control study, 92 GD patients were randomized into a Yingliu mixture treatment and a control treatment group, both receiving methimazole. Both treatments lasted for 12 weeks and outcome parameter were thyroid function, thyroid autoantibodies, TCM symptome scores and safety indicators. Results: The clinical efficiency of the Yingliu mixture-methimazole combination was 92.5% vs. 82.5% (P < 0.05) of the solely methimazole medication group. After 12 weeks treatments the Yingliu mixture in combination with methimazole improved free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyroid-stimulating hormone (TSH) receptor antibody (TRAb) and thyroglobulin antibody (TGAb) values significantly more than methimazole alone and TCM symptome scores were significant lower after 12 week treatment in the Yingliu mixture- methimazole group (P < 0.05). The thyroid enlargement (21 vs. 10, P < 0.05), fatigue (39 vs. 30, P < 0.01) and dry mouth symptoms (37 vs. 29, P < 0.05) were superior improved in the Yingliu than in the control medication group, respectively. There was no significant difference regarding safety evaluations between both treatment groups (P = 0.499). Conclusion: Yingliu mixture as combined medication with methimazole can significantly improve the outcome of a solely methimazole application for GD treatments. PMID:26131218

  18. Low-power laser efficacy in peripheral nerve lesion treatment

    NASA Astrophysics Data System (ADS)

    Antipa, Ciprian; Nacu, Mihaela; Bruckner, Ion I.; Bunila, Daniela; Vlaiculescu, Mihaela; Pascu, Mihail-Lucian; Ionescu, Elena

    1998-07-01

    In order to establish the low energy laser (LEL) effects on nervous tissue regeneration in clinical practice, we evaluated in double blind, placebo controlled study, the efficacy of LEL in the functional recovery of 46 patients with distal forearm post- traumatic nerve lesion, after surgical suture. The patients were divided into two groups: A-26 patients were treated with LEL; B- 20 patients, as control, were treated with placebo lasers and classical medical and physical therapy. Lasers used were: HeNe, 632.5 nm wavelength, 2 mW power, and GaAlAs diode laser, 880 nm wavelength, pulsed emission with an output power about 3 mW. Before, during and after the treatment, electromyography (EMG) and electroneurography (ENG) were done in order to measure objectively the efficacy of the treatment. We obtained good results after 4 - 5 months at 80.7% patients from group A and about the same results at 70% patients from group B, but after at least 8 months. The good results were noticed concerning the improvement of EMG and ENG registrations and on the involution of pain, inflammations, movements and force of the fingers. Finally we can say that the favorable results were obtained in at least half the time with LEL treatment faster than with classical therapy.

  19. Comparison of Cantharidin Toxicity in Breast Cancer Cells to Two Common Chemotherapeutics

    PubMed Central

    Kern, Katie M.; Schroeder, Jennifer R.

    2014-01-01

    As part of a larger study synthesizing a more directed form of chemotherapy, we have begun to assess the efficacy of different potential toxins that could be delivered locally rather than systemically. In doing so, we hope to reduce the systemic side effects commonly observed, while maintaining a high level of toxicity and eliminating the need for metabolic alterations. In a search for this more efficient method for killing cancerous cells, we have begun studying cantharidin, a toxin used in traditional Chinese medicine, as a potential chemotherapeutic. Using an MTT cell viability assay, the toxicity of cantharidin was compared to both cyclophosphamide and paclitaxel in three different breast cancer cell lines: MCF-7, MDA-MB-231, and SK-BR-3. Increasing the concentration of chemotherapy drugs did decrease cell viability in all cell lines when cantharidin and cyclophosphamide were applied; however differences for paclitaxel were cell-specific. Additionally, cantharidin exhibited the highest decrease in cell viability regardless of cell type, indicating it may be a much more potent and less specific chemotherapeutic. These results will help us move forward in developing a potentially more potent treatment for breast cancer that might eliminate the need for subtype-specific treatments. PMID:25302124

  20. Self-Efficacy and Illicit Opioid Use in a 180-Day Methadone Detoxification Treatment.

    ERIC Educational Resources Information Center

    Reilly, Patrick M.; And Others

    1995-01-01

    Studied self-efficacy and treatment outcomes in a sample of opioid addicts. Results show self-efficacy influenced subsequent drug use in parallel with previous behavior. Suggests that psychological constructs like self-efficacy may hold promise for understanding and decreasing illicit opioid use during long-term methadone detoxification treatment.…

  1. [Special recommendations for lipid-lowering treatment: efficacy and safety].

    PubMed

    Martinez, Tania Leme da Rocha; Nascimento, Helena Maria do

    2005-10-01

    Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.

  2. Active nanodiamond hydrogels for chemotherapeutic delivery.

    PubMed

    Huang, Houjin; Pierstorff, Erik; Osawa, Eiji; Ho, Dean

    2007-11-01

    Nanodiamond materials can serve as highly versatile platforms for the controlled functionalization and delivery of a wide spectrum of therapeutic elements. In this work, doxorubicin hydrochloride (DOX), an apoptosis-inducing drug widely used in chemotherapy, was successfully applied toward the functionalization of nanodiamond materials (NDs, 2-8 nm) and introduced toward murine macrophages as well as human colorectal carcinoma cells with preserved efficacy. The adsorption of DOX onto the NDs and its reversible release were achieved by regulating Cl- ion concentration, and the NDs were found to be able to efficiently ferry the drug inside living cells. Comprehensive bioassays were performed to assess and confirm the innate biocompatibility of the NDs, via real-time quantitative polymerase chain reaction (RT-PCR), and electrophoretic DNA fragmentation as well as MTT analysis confirmed the functional apoptosis-inducing mechanisms driven by the DOX-functionalized NDs. We extended the applicability of the DOX-ND composites toward a translational context, where MTT assays were performed on the HT-29 colon cancer cell line to assess DOX-ND induced cell death and ND-mediated chemotherapeutic sequestering for potential slow/sustained released capabilities. These and other medically relevant capabilities enabled by the NDs forge its strong potential as a therapeutically significant nanomaterial.

  3. Suppression of STN1 enhances the cytotoxicity of chemotherapeutic agents in cancer cells by elevating DNA damage

    PubMed Central

    Zhou, Qing; Chai, Weihang

    2016-01-01

    DNA damage-inducing agents are among the most effective treatment regimens in clinical chemotherapy. However, drug resistance and severe side effects caused by these agents greatly limit their efficacy. Sensitizing malignant cells to chemotherapeutic agents has long been a goal of chemotherapy. In the present study, suppression of STN1, a gene important for safeguarding genome stability, potentiated the anticancer effect of chemotherapeutic agents in tumor cells. Using multiple cancer cells from a variety of origins, it was observed that downregulation of STN1 resulted in a significant decrease in the half maximal inhibitory concentration values of several conventional anticancer agents. When cells are treated with anticancer agents, STN1 suppression leads to a decline in colony formation and diminished anchorage-independent growth. Furthermore, it was additionally observed that STN1 knockdown augmented the levels of DNA damage caused by damage-inducing agents. The present study concluded that suppression of STN1 enhances the cytotoxicity of damage-inducing chemotherapeutic agents by increasing DNA damage in cancer cells. PMID:27446354

  4. Chemotherapeutic effect of Berberis integerrima hydroalcoholic extract on colon cancer development in the 1,2-dimethyl hydrazine rat model.

    PubMed

    Malayeri, Mohammad R Mohammadi; Dadkhah, Abolfazl; Fatemi, Faezeh; Dini, Salome; Torabi, Fatemeh; Tavajjoh, Mohammad M; Rabiei, Javad

    2016-01-01

    The aim of this study was to investigate the efficacy of a Berberis integerrima hydroalcoholic extract as a chemotherapeutic agent in colon carcinogenesis in the rat induced by 1,2-dimethyl hydrazine (DMH). Male Wistar rats were divided into five groups: a negative control group without DMH treatment; a control group injected DMH (20 mg/kg b.w); two groups receiving B. integerrima extract (50 and 100 mg/kg b.w), concomitant with injected DMH, as chemotherapeutic groups; a positive control group receiving 5-fluorouracil (5-FU) along with DMH. The effects of the extracts were determined by assessment of hepatic malondialdehyde (MDA), glutathione (GSH), ferric reducing ability of plasma (FRAP), and the activities of hepatic glutathione S-transferase and cytochrome P450 (GST and CYP450). Additionally, colon tissues were assessed for colonic β-catenin and histopathological analysis. In DMH-treated rats, the extracts partially normalized the levels of FRAP, CYP450, β-catenin, and GST. Likewise, formation of aberrant crypt foci (ACF) in colon tissue of DMH-treated was reduced by the extracts. Thus, the extracts possess chemotherapeutic activity against colon carcinogenesis.

  5. Human toxoplasmosis-Searching for novel chemotherapeutics.

    PubMed

    Antczak, Magdalena; Dzitko, Katarzyna; Długońska, Henryka

    2016-08-01

    The protozoan Toxoplasma gondii, an obligate intracellular parasite, is an etiological agent of human and animal toxoplasmosis. Treatment regimens for T. gondii-infected patients have not essentially changed for years. The most common chemotherapeutics used in the therapy of symptomatic toxoplasmosis are a combination of pyrimethamine and sulfadiazine plus folinic acid or a combination of pyrimethamine with lincosamide or macrolide antibiotics. To protect a fetus from parasite transplacental transmission, therapy of pregnant women is usually based on spiramycin, which is quite safe for the organism, but not efficient in the treatment of infected children. Application of recommended drugs limits replication of T. gondii, however, it may be associated with numerous an severe adverse effects. Moreover, medicines have no impact on the tissue cysts of the parasite located predominantly in a brain and muscles. Thus, there is urgent need to develop new drugs and establish "gold standard" treatment. In this review classical treatment of toxoplasmosis as well as potential compounds active against T. gondii have been discussed. For two last decades studies on the development of new anti-T. gondii medications have been focused on both natural and novel synthetic compounds based on existing chemical scaffolds. They have revealed several promising drug candidates characterized by a high selectivity, the low IC50 (the half maximal inhibitory concentration) and low cytotoxicity towards host cells. These drugs are expected to replace or supplement current anti-T. gondii drug arsenal soon. PMID:27470411

  6. Analgesic Placebo Treatment Perceptions: Acceptability, Efficacy, and Knowledge

    PubMed Central

    Kisaalita, Nkaku R.; Robinson, Michael E.

    2012-01-01

    Current evidence supports the efficacy of placebo analgesia and illustrates that patients may be open to placebo use despite uncertainty regarding its mechanisms. Debate persists, however, concerning the ethics of placebo treatments. The purpose of the present web-based study was to expand upon the empirical literature on placebo analgesia ethics and acceptability. Participants (n = 100) provided their definition of a placebo and responded to 24 questions addressing placebo analgesia perceived knowledge, acceptability, effectiveness, and likelihood of placebo use among different healthcare providers. Results support previous research on the effects of placebo on negative mood and healthcare provider attributions, with findings illustrating that negative consequences of administration were largely mitigated by a beneficial treatment outcome. Results showed that participants conceptualized placebo as predominately “inert” and were mixed regarding interpretations of placebo effectiveness. Though acceptability ratings were dependent on the context of placebo administration, participants endorsing even moderate placebo acceptability were more open to placebo interventions and reported overall more positive treatment outcomes. Participants believed that placebos were used differentially among healthcare providers. Additional studies are needed to determine if placebo education can beneficially impact perceptions of placebo analgesia knowledge, acceptability, and treatment effectiveness. PMID:22854011

  7. Efficacy of azithromycin in the treatment of childhood typhoid Fever.

    PubMed

    Islam, M N; Rahman, M E; Rouf, M A; Islam, M N; Khaleque, M A; Siddika, M; Hossain, M A

    2007-07-01

    An intervention study was carried out in Paediatric wards for a period of one year from January 2003 to December 2003 to determine the efficacy and safety of azithromycin in the treatment of uncomplicated childhood typhoid fever. A total of 50 cases were enrolled in the study. The inclusion criteria of the cases were: documented fever for more than 7 days plus two or more of the following clinical features: toxic appearance, abdominal tenderness, hepatomegaly, splenomegaly, diarrhoea, constipation and coated tongue plus positive Widal test and/or blood culture positivity. Patients who had complication like gastrointestinal tract (GIT) haemorrhage; intestinal perforation and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg /day for a period of 07 days. The time to defervescence was 3.82+/-1.49 days. The minimum defervescence time was 02 days and maximum was 07 days. Clinical cure rate was 94%. No serious adverse effect was noted related to azithromycin therapy except nausea, vomiting, and jaundice. Prior treatment with antibiotics did not affect defervescence time (P>0.05). Pre-treatment febrile period has got positive and linear correlation with clinical response (r = +0.593). It was found that once daily administration of oral azithromycin for seven days in the treatment of uncomplicated typhoid fever was effective and reasonably safe. PMID:17703150

  8. Efficacy of Dapoxetine in the Treatment of Premature Ejaculation

    PubMed Central

    McMahon, Chris G.

    2011-01-01

    Introduction Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological factors. Pharmacotherapy of PE with off-label antidepressant SSRI drugs is common. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill a unmet treatment need. Aim To review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. Methods MEDLINE and the proceedings of major international and regional scientific meetings during the period 1994–2010 were searched for publications or abstracts using the word dapoxetine in the title, abstract or keywords. This search was then manually cross-referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase 1, 2 and 3 efficacy and safety studies and drug-interaction studies. Results Dapoxetine is a potent selective serotonin re-uptake inhibitor, which is administered on-demand 1–3 hours prior to planned sexual contact. Dapoxetine is rapidly absorbed and eliminated, resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in 5 randomized, double-blind, placebo-controlled studies in 6081 men aged ≥18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, clinical global impression of change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P < 0.001 for all). The most common treatment related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (586% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI

  9. The influence of self-efficacy expectations on the treatment of preorgasmic women.

    PubMed

    Bogat, G A; Hamernik, K; Brooks, L A

    1987-01-01

    One of the most successful treatments developed for women who never or rarely experience orgasm is Barbach's preorgasmic treatment program. We propose that Bandura's theory of self-efficacy provides a useful framework for understanding the success of Barbach's program. This pilot study was designed to determine whether treatment affects subjects' Certainty of and Comfort with Sexual Efficacy. Treatment (n = 5) and control (n = 6) subjects completed prepoint and postpoint instruments that measured sexual efficacy expectations, body satisfaction, locus of control, and assertiveness. Although most postpoint differences were nonsignificant (probably due to small sample size), intriguing trends emerged. In particular, treatment seemed to contribute to increased Certainty of Sexual Efficacy and body satisfaction.

  10. Design and synthesis of a MAO-B-selectively activated prodrug based on MPTP: a mitochondria-targeting chemotherapeutic agent for treatment of human malignant gliomas.

    PubMed

    Sharpe, Martyn A; Han, Junyan; Baskin, Alexandra M; Baskin, David S

    2015-04-01

    Malignant gliomas, including glioblastomas, are extremely difficult to treat. The median survival for glioblastoma patients with optimal therapeutic intervention is 15 months. We developed a novel MAO-B-selectively activated prodrug, N,N-bis(2-chloroethyl)-2-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)propanamide (MP-MUS), for the treatment of gliomas based on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The design of neutral MP-MUS involved the use of a seeker molecule capable of binding to mitochondrial MAO-B, which is up-regulated ≥fourfold in glioma cells. Once the binding occurs, MP-MUS is converted into a positively charged moiety, P(+) -MUS, which accumulates inside mitochondria at a theoretical maximal value of 1000:1 gradient. The LD50 of MP-MUS against glioma cells is 75 μM, which is two- to threefold more potent than temozolomide, a primary drug for gliomas. Importantly, MP-MUS was found to be selectively toxic toward glioma cells. In the concentration range of 150-180 μM MP-MUS killed 90-95 % of glioma cells, but stimulated the growth of normal human astrocytes. Moreover, maturation of MP-MUS is highly dependent on MAO-B, and inhibition of MAO-B activity with selegiline protected human glioma cells from apoptosis. PMID:25677185

  11. Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins.

    PubMed

    de Oliveira, M S; de Assis, D B; Freire, M P; Boas do Prado, G V; Machado, A S; Abdala, E; Pierrotti, L C; Mangini, C; Campos, L; Caiaffa Filho, H H; Levin, A S

    2015-02-01

    Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy. PMID:25599940

  12. Efficacy of dry needling for treatment of myofascial pain syndrome.

    PubMed

    Fogelman, Yacov; Kent, John

    2015-01-01

    Myofascial pain is a major cause of musculoskeletal regional pain. Myofascial pain, which is a high-prevalence but eminently treatable condition, is almost universally underdiagnosed by physicians and undertreated by physical therapy modalities. Large numbers of patients can be left suffering in chronic pain for years. Dry needling, also referred to as Intramuscular Stimulation, is a method in the arsenal of pain management which has been known for almost 200 years in Western medicine, yet has been almost completely ignored. With the increase in research in this field over the past two decades, there are many high-quality studies that demonstrate dry needling to be an effective and safe method for the treatment of myofascial pain when diagnosed and treated by adequately-trained physicians or physical therapists. This article provides an overview of recent literature regarding the treatment of myofascial pain syndrome, evidence for the efficacy of dry needling as a central component of its management, and a glimpse at developments in recent imaging methods to aid in the treatment of these problems.

  13. Efficacy of Viola odorata in Treatment of Chronic Insomnia

    PubMed Central

    Feyzabadi, Zohre; Jafari, Farhad; Kamali, Seyed Hamid; Ashayeri, Hassan; Badiee Aval, Shapour; Esfahani, Mohammad Mahdi; Sadeghpour, Omid

    2014-01-01

    Background: Insomnia is the most common sleep disorder that reduces quality of life. Objectives: Due to side effects of hypnotic drug and the increasing demand for alternative medicine substitutes, violet oil (VO) was used in this study. VO is a known medication in Iranian traditional medicine that induces sleep in insomniac patients. Patients and Methods: This study was conducted as an experimental pretest-posttest evaluation on VO efficacy in 50 patients with chronic insomnia in Iranian Traditional Medicine Clinic of Mashhad University of Medical Sciences, Mashhad, Iran. Treatment consisted of intranasal drop of VO, two drops containing 66 mg of VO in each nostril nightly before sleeping for one month. All patients were asked to complete an Insomnia Severity Index (ISI) questionnaire before the start of the trial and after one month of treatment. Results: Improvements in sleep and ISI scores were significantly greater in patients after a month receiving VO drop in comparison with before starting treatment (P < 0.05). A few patients reported some complications about VO consumption, most of which were mild and no serious adverse event was encountered. Conclusions: VO can be presented as a safe, well-tolerated, and effective herbal preparation in patients with chronic insomnia. PMID:25763239

  14. Abstinence Self-Efficacy and Abstinence 1 Year After Substance Use Disorder Treatment

    ERIC Educational Resources Information Center

    Ilgen, Mark; McKellar, John; Tiet, Quyen

    2005-01-01

    To better understand the relationship between abstinence self-efficacy and treatment outcomes in substance use disorder patients, experts in the field need more information about the levels of abstinence self-efficacy most predictive of treatment outcomes. Participants (N = 2,967) from 15 residential substance use disorder treatment programs were…

  15. Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.

    PubMed

    Giladi, Moshe; Weinberg, Uri; Schneiderman, Rosa S; Porat, Yaara; Munster, Michal; Voloshin, Tali; Blatt, Roni; Cahal, Shay; Itzhaki, Aviran; Onn, Amir; Kirson, Eilon D; Palti, Yoram

    2014-10-01

    Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Common treatment modalities for NSCLC include surgery, radiotherapy, chemotherapy, and, in recent years, the clinical management paradigm has evolved with the advent of targeted therapies. Despite such advances, the impact of systemic therapies for advanced disease remains modest, and as such, the prognosis for patients with NSCLC remains poor. Standard modalities are not without their respective toxicities and there is a clear need to improve both efficacy and safety for current management approaches. Tumor-treating fields (TTFields) are low-intensity, intermediate-frequency alternating electric fields that disrupt proper spindle microtubule arrangement, thereby leading to mitotic arrest and ultimately to cell death. We evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. We investigated the response of Lewis lung carcinoma and KLN205 squamous cell carcinoma in mice treated with TTFields in combination with pemetrexed, cisplatin, or paclitaxel and compared these to the efficacy observed in mice exposed only to the single agents. Combining TTFields with these therapeutic agents enhanced treatment efficacy in comparison with the respective single agents and control groups in all animal models. Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.

  16. From traditional medicine to witchcraft: why medical treatments are not always efficacious.

    PubMed

    Tanaka, Mark M; Kendal, Jeremy R; Laland, Kevin N

    2009-01-01

    Complementary medicines, traditional remedies and home cures for medical ailments are used extensively world-wide, representing more than US$60 billion sales in the global market. With serious doubts about the efficacy and safety of many treatments, the industry remains steeped in controversy. Little is known about factors affecting the prevalence of efficacious and non-efficacious self-medicative treatments. Here we develop mathematical models which reveal that the most efficacious treatments are not necessarily those most likely to spread. Indeed, purely superstitious remedies, or even maladaptive practices, spread more readily than efficacious treatments under specified circumstances. Low-efficacy practices sometimes spread because their very ineffectiveness results in longer, more salient demonstration and a larger number of converts, which more than compensates for greater rates of abandonment. These models also illuminate a broader range of phenomena, including the spread of innovations, medical treatment of animals, foraging behaviour, and self-medication in non-human primates.

  17. From Traditional Medicine to Witchcraft: Why Medical Treatments Are Not Always Efficacious

    PubMed Central

    Tanaka, Mark M.; Kendal, Jeremy R.; Laland, Kevin N.

    2009-01-01

    Complementary medicines, traditional remedies and home cures for medical ailments are used extensively world-wide, representing more than US$60 billion sales in the global market. With serious doubts about the efficacy and safety of many treatments, the industry remains steeped in controversy. Little is known about factors affecting the prevalence of efficacious and non-efficacious self-medicative treatments. Here we develop mathematical models which reveal that the most efficacious treatments are not necessarily those most likely to spread. Indeed, purely superstitious remedies, or even maladaptive practices, spread more readily than efficacious treatments under specified circumstances. Low-efficacy practices sometimes spread because their very ineffectiveness results in longer, more salient demonstration and a larger number of converts, which more than compensates for greater rates of abandonment. These models also illuminate a broader range of phenomena, including the spread of innovations, medical treatment of animals, foraging behaviour, and self-medication in non-human primates. PMID:19367333

  18. Physician Burnout: Improving Treatment Efficacy with Virtual Reality.

    PubMed

    Wiederhold, Brenda K; Riva, Giuseppe; Gaggioli, Andrea; Wiederhold, Mark D

    2016-01-01

    Creating a significant negative impact on both their quality of life and the quality of patient care with an evident economical burden for the healthcare system, there is a growing concern over physician burnout. The range of interventions and treatments that have been used to address this problem, however, appear quite fragmented and lack compelling efficacy. We describe the main factors known to contribute to the development of physician burnout as well as currently available treatments. Studies seem to indicate that both specialisation area as well as personality traits may contribute to the manifestation. The highest risk specialties appear to be critical care physicians, emergency physicians, oncologists and internal medicine physicians, while the highest risk personality attributes are high neuroticism, low agreeableness, introversion, and negative affectivity. In addition, being exceedingly enthusiastic about one's work and having high aspirations at work, with an idealistic approach, also serve as factors which contribute to increased risk of burnout, and in particular for those who are new to the occupation. PMID:27046622

  19. Use of mixed-treatment-comparison methods in estimating efficacy of treatments for heavy menstrual bleeding

    PubMed Central

    2013-01-01

    Background A variety of pharmacological and surgical treatments have been developed for heavy menstrual bleeding (HMB), which can have negative physical, social, psychological, and economic consequences. We conducted a systematic literature review and mixed-treatment-comparison (MTC) meta-analysis of available data from randomized controlled trials (RCTs) to derive estimates of efficacy for 8 classes of treatments for HMB, to inform health-economic analysis and future studies. Methods A systematic review identified RCTs that reported data on menstrual blood loss (MBL) at baseline and one or more follow-up times. Eight treatment classes were considered: COCs, danazol, endometrial ablation, LNG-IUS, placebo, progestogens given for less than 2 weeks out of 4 during the menstrual cycle, progestogens given for close to 3 weeks out of 4, and TXA. The primary measure of efficacy was the proportion of women who achieved MBL < 80 mL per cycle (month), as measured by the alkaline hematin method. A score less than 100 on an established pictorial blood-loss assessment chart (PBAC) was considered an acceptable substitute for MBL < 80 mL. Estimates of efficacy by treatment class and time were obtained from a Bayesian MTC model. The model also included effects for treatment class, study, and the combination of treatment class and study and an adjustment for baseline mean MBL. Several methodological challenges complicated the analysis. Some trials reported various summary statistics for MBL or PBAC, requiring estimation (with less precision) of % MBL < 80 mL or % PBAC < 100. Also, reported follow-up times varied substantially. Results The evidence network involved 34 RCTs, with follow-up times from 1 to 36 months. Efficacy at 3 months of follow-up (estimated as the posterior median) ranged from 87.5% for the levonorgestrel-releasing intrauterine system (LNG-IUS) to 14.2% for progestogens administered for less than 2 weeks out of 4 in the menstrual cycle. The 95% credible intervals

  20. Pharmacoeconomic evaluation of new treatments: efficacy versus effectiveness studies?

    PubMed Central

    Bombardier, C; Maetzel, A

    1999-01-01

    The juxtaposition of economic and clinical evaluation raises new issues in the design of clinical trials. Recent pharmacoeconomic guidelines provide some direction, but do not deal with the appropriate timing of economic evaluations in the drug developmental process. Ideally, pharmacoeconomic data should be available at the time of the regulatory and formulary decision making. Current pivotal phase III trials do not provide these data; they are designed to test safety and efficacy (does the drug work under optimal circumstances?) and not to answer questions about the effectiveness of a drug, the more relevant question for economic analysis (does the drug work in usual care?). The use of more "naturalistic" designs for some phase III randomised trials has been suggested. These so called "effectiveness trials" more closely reflect routine clinical practice. They use a more flexible dosage regimen, and a "usual care" instead of a placebo comparator. Patients randomised are more representative of actual practice and outcomes include quality of life and utility measures. They are more suited to provide the data needed to estimate the real benefit of the treatment in actual care. When costs are applied and compared with these benefits, you can estimate the efficiency of allocating resources to this new drug. Increasing the use of effectiveness trials in phase III would decrease the need for economic modelling.

 PMID:10577979

  1. Culture at a Higher Temperature Mildly Inhibits Cancer Cell Growth but Enhances Chemotherapeutic Effects by Inhibiting Cell-Cell Collaboration.

    PubMed

    Zhu, Shengming; Wang, Jiangang; Xie, Bingkun; Luo, Zhiguo; Lin, Xiukun; Liao, D Joshua

    2015-01-01

    Acute febrile infections have historically been used to treat cancer. To explore the underlying mechanism, we studied chronic effects of fever on cancer cell growth and chemotherapeutic efficacy in cell culture. We found that culturing cancer cells at 39°C mildly inhibited cell growth by arresting the cells at the G1 phase of the cell cycle. When cells were seeded in culture dishes at a lower density, e.g. about 1000-2000 cells per 35-mm dish, the growth inhibition was much greater, manifested as many fewer cell colonies in the 39°C dishes, compared with the results at a higher density seeding, e.g. 20,000 cells per dish, suggesting that cell-cell collaboration as the Allee effect in cell culture is inhibited at 39°C. Withdrawal of cells from serum enhanced the G1 arrest at 39°C and, for some cell lines such as A549 lung cancer cells, serum replenishment failed to quickly drive the cells from the G1 into the S and G2-M phases. Therapeutic effects of several chemotherapeutic agents, including clove bud extracts, on several cancer cell lines were more potent at 39°C than at 37°C, especially when the cells were seeded at a low density. For some cell lines and some agents, this enhancement is long-lasting, i.e. continuing after the cessation of the treatment. Collectively these results suggest that hyperthermia may inhibit cancer cell growth by G1 arrest and by inhibition of cell-cell collaboration, and may enhance the efficacy of several chemotherapeutic agents, an effect which may persist beyond the termination of chemotherapy. PMID:26495849

  2. Culture at a Higher Temperature Mildly Inhibits Cancer Cell Growth but Enhances Chemotherapeutic Effects by Inhibiting Cell-Cell Collaboration

    PubMed Central

    Zhu, Shengming; Wang, Jiangang; Xie, Bingkun; Luo, Zhiguo; Lin, Xiukun; Liao, D. Joshua

    2015-01-01

    Acute febrile infections have historically been used to treat cancer. To explore the underlying mechanism, we studied chronic effects of fever on cancer cell growth and chemotherapeutic efficacy in cell culture. We found that culturing cancer cells at 39°C mildly inhibited cell growth by arresting the cells at the G1 phase of the cell cycle. When cells were seeded in culture dishes at a lower density, e.g. about 1000–2000 cells per 35-mm dish, the growth inhibition was much greater, manifested as many fewer cell colonies in the 39°C dishes, compared with the results at a higher density seeding, e.g. 20,000 cells per dish, suggesting that cell-cell collaboration as the Allee effect in cell culture is inhibited at 39°C. Withdrawal of cells from serum enhanced the G1 arrest at 39°C and, for some cell lines such as A549 lung cancer cells, serum replenishment failed to quickly drive the cells from the G1 into the S and G2-M phases. Therapeutic effects of several chemotherapeutic agents, including clove bud extracts, on several cancer cell lines were more potent at 39°C than at 37°C, especially when the cells were seeded at a low density. For some cell lines and some agents, this enhancement is long-lasting, i.e. continuing after the cessation of the treatment. Collectively these results suggest that hyperthermia may inhibit cancer cell growth by G1 arrest and by inhibition of cell-cell collaboration, and may enhance the efficacy of several chemotherapeutic agents, an effect which may persist beyond the termination of chemotherapy. PMID:26495849

  3. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    SciTech Connect

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E. . E-mail: cng@ohri.ca

    2005-05-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  4. Treatment Implications Derived from Self-Efficacy Research with Children.

    ERIC Educational Resources Information Center

    Roth, William G.

    Self-efficacy, a person's perceived capacity to execute a behavior required to produce a desired oucome, can affect motivation and behavior. It appears that individuals gain self-efficacy information from performance accomplishments, vicarious experience, verbal persuasion, and emotional arousal. Effective clinical interventions must promote…

  5. Predicting chemotherapeutic drug combinations through gene network profiling

    PubMed Central

    Nguyen, Thi Thuy Trang; Chua, Jacqueline Kia Kee; Seah, Kwi Shan; Koo, Seok Hwee; Yee, Jie Yin; Yang, Eugene Guorong; Lim, Kim Kiat; Pang, Shermaine Yu Wen; Yuen, Audrey; Zhang, Louxin; Ang, Wee Han; Dymock, Brian; Lee, Edmund Jon Deoon; Chen, Ee Sin

    2016-01-01

    Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent, and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells. PMID:26791325

  6. Willpower versus "skillpower": Examining how self-efficacy works in treatment for marijuana dependence.

    PubMed

    Litt, Mark D; Kadden, Ronald M

    2015-09-01

    Self-efficacy has repeatedly been demonstrated to be a robust predictor of outcomes in the treatment of marijuana use disorders. It is not clear, however, how increases in confidence in ability to refrain from use get translated into actual improvements in drug-related outcomes. Marlatt, among others, viewed the acquisition and use of coping skills as the key to behavior change, and self-efficacy as a cognitive state that enabled coping. But that model of behavior change has not been supported, and few studies have shown that the effects of self-efficacy are mediated by coping or by other processes. The current study combined 3 marijuana treatment trials comprising 901 patients to examine the relationships between self-efficacy, coping, and potential mediators, to determine if the effects of self-efficacy on outcomes could be explained. Results of multilevel models indicated that self-efficacy was a strong predictor of adaptive outcomes in all trials, even when no active treatment was provided. Tests of mediation showed that effects of self-efficacy on marijuana use and on marijuana-related problems were partially mediated by use of coping skills and by reductions in emotional distress, but that direct effects of self-efficacy remained largely unexplained. The results are seen as supportive of efforts to improve coping skills and reduce distress in marijuana treatment, but also suggest that additional research is required to discover what is actually occurring when substance use changes, and how self-efficacy enables those changes.

  7. Effect of ceritinib (LDK378) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo

    PubMed Central

    Hu, Jing; Zhang, Xu; Wang, Fang; Wang, Xiaokun; Yang, Ke; Xu, Meng; To, Kenneth K.W.

    2015-01-01

    Multidrug resistance (MDR) is the leading cause of treatment failure in cancer chemotherapy. The overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2, play a key role in mediating MDR by pumping anticancer drugs out from cancer cells. Ceritinib (LDK378) is a second-generation tyrosine kinase inhibitor of anaplastic lymphoma kinase (ALK) currently in phase III clinical trial for the treatment of non-small cell lung cancer. Here, we found that ceritinib remarkably enhanced the efficacy of chemotherapeutic drugs in ABCB1 or ABCG2 over-expressing cancer cells in vitro and in vivo. Ceritinib significantly increased the intracellular accumulation of chemotherapeutic agents such as doxorubicin (DOX) by inhibiting ABCB1 or ABCG2-mediated drug efflux in the transporters-overexpressing cells. Mechanistically, ceritinib is likely a competitive inhibitor of ABCB1 and ABCG2 because it competed with [125I]-iodoarylazidoprazosin for photo affinity labeling of the transporters. On the other hand, at the transporters-inhibiting concentrations, ceritinib did not alter the expression level of ABCB1 and ABCG2, and phosphorylation status of AKT and ERK1/2. Thus the findings advocate further clinical investigation of combination chemotherapy of ceritinib and other conventional chemotherapeutic drugs in chemo-refractory cancer patients. PMID:26556876

  8. Testing the Efficacy of Theoretically Derived Improvements in the Treatment of Social Phobia

    ERIC Educational Resources Information Center

    Rapee, Ronald M.; Gaston, Jonathan E.; Abbott, Maree J.

    2009-01-01

    Recent theoretical models of social phobia suggest that targeting several specific cognitive factors in treatment should enhance treatment efficacy over that of more traditional skills-based treatment programs. In the current study, 195 people with social phobia were randomly allocated to 1 of 3 treatments: standard cognitive restructuring plus in…

  9. Efficacy of medical therapy in treatment of chronic rhinosinusitis.

    PubMed

    Young, Lee C; Stow, Nicholas W; Zhou, Lifeng; Douglas, Richard G

    2012-01-01

    Uncomplicated chronic rhinosinusitis (CRS) is generally treated with medical therapy initially and surgery is contemplated only after medical therapy has failed. However, there is considerable variation in the medical treatment regimens used and studies defining their efficacy are few. The aim of this study was to determine the proportion of patients treated medically who responded sufficiently well so that surgery was not required. Subgroup analysis to identify clinical features that predicted a favorable response to medical therapy was also performed. Eighty patients referred to the Otorhinolaryngology Clinic at North Shore Hospital were treated with a standardized medical therapy protocol (oral prednisone for 3 weeks, oral antibiotics and ongoing saline lavage and intranasal budesonide spray). Symptom scores were collected before and after medical therapy. Clinical features such as presence of polyps, asthma, and aspirin hypersensitivity were recorded. Failure of medical therapy was defined as the persistence of significant CRS symptoms, and those patients who failed medical therapy were offered surgery. Follow-up data were available for 72 (90%) patients. Of this group, 52.5%, (95% CI, 42.7%, 62.2%) failed to respond adequately to medical therapy and were offered surgery. The remaining patients (37.5%) were successfully treated with medical therapy and did not require surgery at the time of follow-up. The premedical therapy symptom scores were significantly higher than the postmedical therapy symptom scores (p < 0.01). The symptom scores of those patients postmedical therapy who proceeded to have surgery were significantly higher than the group who responded well to maximum medical therapy (MMT) and did not require surgery (p < 0.0001). There were no significant differences in the proportion of patients with asthma, aspirin sensitivity, or polyps between the groups failing or not failing MMT. In approximately one-third of patients with CRS, medical therapy

  10. Efficacy of treatments for anxiety disorders: a meta-analysis.

    PubMed

    Bandelow, Borwin; Reitt, Markus; Röver, Christian; Michaelis, Sophie; Görlich, Yvonne; Wedekind, Dirk

    2015-07-01

    To our knowledge, no previous meta-analysis has attempted to compare the efficacy of pharmacological, psychological and combined treatments for the three main anxiety disorders (panic disorder, generalized anxiety disorder and social phobia). Pre-post and treated versus control effect sizes (ES) were calculated for all evaluable randomized-controlled studies (n = 234), involving 37,333 patients. Medications were associated with a significantly higher average pre-post ES [Cohen's d = 2.02 (1.90-2.15); 28,051 patients] than psychotherapies [1.22 (1.14-1.30); 6992 patients; P < 0.0001]. ES were 2.25 for serotonin-noradrenaline reuptake inhibitors (n = 23 study arms), 2.15 for benzodiazepines (n = 42), 2.09 for selective serotonin reuptake inhibitors (n = 62) and 1.83 for tricyclic antidepressants (n = 15). ES for psychotherapies were mindfulness therapies, 1.56 (n = 4); relaxation, 1.36 (n = 17); individual cognitive behavioural/exposure therapy (CBT), 1.30 (n = 93); group CBT, 1.22 (n = 18); psychodynamic therapy 1.17 (n = 5); therapies without face-to-face contact (e.g. Internet therapies), 1.11 (n = 34); eye movement desensitization reprocessing, 1.03 (n = 3); and interpersonal therapy 0.78 (n = 4). The ES was 2.12 (n = 16) for CBT/drug combinations. Exercise had an ES of 1.23 (n = 3). For control groups, ES were 1.29 for placebo pills (n = 111), 0.83 for psychological placebos (n = 16) and 0.20 for waitlists (n = 50). In direct comparisons with control groups, all investigated drugs, except for citalopram, opipramol and moclobemide, were significantly more effective than placebo. Individual CBT was more effective than waiting list, psychological placebo and pill placebo. When looking at the average pre-post ES, medications were more effective than psychotherapies. Pre-post ES for psychotherapies did not differ from pill placebos; this finding cannot be explained by heterogeneity, publication bias or allegiance effects. However, the decision on whether to choose

  11. Efficacy of treatments for anxiety disorders: a meta-analysis.

    PubMed

    Bandelow, Borwin; Reitt, Markus; Röver, Christian; Michaelis, Sophie; Görlich, Yvonne; Wedekind, Dirk

    2015-07-01

    To our knowledge, no previous meta-analysis has attempted to compare the efficacy of pharmacological, psychological and combined treatments for the three main anxiety disorders (panic disorder, generalized anxiety disorder and social phobia). Pre-post and treated versus control effect sizes (ES) were calculated for all evaluable randomized-controlled studies (n = 234), involving 37,333 patients. Medications were associated with a significantly higher average pre-post ES [Cohen's d = 2.02 (1.90-2.15); 28,051 patients] than psychotherapies [1.22 (1.14-1.30); 6992 patients; P < 0.0001]. ES were 2.25 for serotonin-noradrenaline reuptake inhibitors (n = 23 study arms), 2.15 for benzodiazepines (n = 42), 2.09 for selective serotonin reuptake inhibitors (n = 62) and 1.83 for tricyclic antidepressants (n = 15). ES for psychotherapies were mindfulness therapies, 1.56 (n = 4); relaxation, 1.36 (n = 17); individual cognitive behavioural/exposure therapy (CBT), 1.30 (n = 93); group CBT, 1.22 (n = 18); psychodynamic therapy 1.17 (n = 5); therapies without face-to-face contact (e.g. Internet therapies), 1.11 (n = 34); eye movement desensitization reprocessing, 1.03 (n = 3); and interpersonal therapy 0.78 (n = 4). The ES was 2.12 (n = 16) for CBT/drug combinations. Exercise had an ES of 1.23 (n = 3). For control groups, ES were 1.29 for placebo pills (n = 111), 0.83 for psychological placebos (n = 16) and 0.20 for waitlists (n = 50). In direct comparisons with control groups, all investigated drugs, except for citalopram, opipramol and moclobemide, were significantly more effective than placebo. Individual CBT was more effective than waiting list, psychological placebo and pill placebo. When looking at the average pre-post ES, medications were more effective than psychotherapies. Pre-post ES for psychotherapies did not differ from pill placebos; this finding cannot be explained by heterogeneity, publication bias or allegiance effects. However, the decision on whether to choose

  12. The Efficacy of Coerced Treatment for Offenders: An Evaluation of Two Residential Forensic Drug and Alcohol Treatment Programs.

    ERIC Educational Resources Information Center

    Baird, Francis X.; Frankel, Arthur J.

    2001-01-01

    Reviews the history of community-based treatment for offenders with drug and alcohol addiction. Describes the treatment regimen in two residential programs for offenders with drug and alcohol problems, including a description of the components of the residential treatment model utilized in these two programs. Findings support the efficacy of…

  13. Effect of Self-Efficacy on Dropout from Obesity Treatment.

    ERIC Educational Resources Information Center

    Mitchell, Christine; Stuart, Richard B.

    1984-01-01

    Subjects (N=414) averaging 51 pounds overweight were followed by telephone questionnaire for the first 12 weeks of their Weight Watchers participation. Dropouts (N=101) reported lower self-efficacy at the beginning of their memberships and were less likely to feel successful in weight control although their weight loss did not differ…

  14. Neuropilin-1-targeted gold nanoparticles enhance therapeutic efficacy of platinum(IV) drug for prostate cancer treatment.

    PubMed

    Kumar, Anil; Huo, Shuaidong; Zhang, Xu; Liu, Juan; Tan, Aaron; Li, Shengliang; Jin, Shubin; Xue, Xiangdong; Zhao, YuanYuan; Ji, Tianjiao; Han, Lu; Liu, Hong; Zhang, XiaoNing; Zhang, Jinchao; Zou, Guozhang; Wang, Tianyou; Tang, Suoqin; Liang, Xing-Jie

    2014-05-27

    Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known antioxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the antioxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered specifically to prostate cancer cells in vitro. Targeted peptide ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when functionalized with the targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1, as confirmed through inductively coupled plasma mass spectrometry and confocal microscopy. The nanocarriers have effective anticancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with platinum(IV)-functionalized gold nanoparticles along with a targeting peptide hold significant promise for future cancer treatment.

  15. Neuropilin-1-targeted gold nanoparticles enhance therapeutic efficacy of platinum(IV) drug for prostate cancer treatment.

    PubMed

    Kumar, Anil; Huo, Shuaidong; Zhang, Xu; Liu, Juan; Tan, Aaron; Li, Shengliang; Jin, Shubin; Xue, Xiangdong; Zhao, YuanYuan; Ji, Tianjiao; Han, Lu; Liu, Hong; Zhang, XiaoNing; Zhang, Jinchao; Zou, Guozhang; Wang, Tianyou; Tang, Suoqin; Liang, Xing-Jie

    2014-05-27

    Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known antioxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the antioxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered specifically to prostate cancer cells in vitro. Targeted peptide ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when functionalized with the targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1, as confirmed through inductively coupled plasma mass spectrometry and confocal microscopy. The nanocarriers have effective anticancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with platinum(IV)-functionalized gold nanoparticles along with a targeting peptide hold significant promise for future cancer treatment. PMID:24730557

  16. [Thinking on the efficacy evaluation of TCM for treatment of heart failure].

    PubMed

    Wang, Yong-xia; Zhu, Ming-jun

    2008-12-01

    Through dissertating the current status and trend in efficacy evaluation of traditional and Western medicine for treatment of heart failure, aiming at the difference between TCM and Western medicine in efficacy evaluation and existent problems for diagnosis and treatment of heart failure. The authors proposed to establish a method for evaluating TCM clinical studies, a systematic method and thinking of indexes rating, depending upon the guidance of clinical methodologies of systematology, clinical epidemiology and evidence-based medicine, to make the efficacy evaluation founded upon the superiority of TCM and meeting to the international requisition, thus to facilitate the goingahead of TCM to the world.

  17. Assessment of linezolid efficacy, safety and tolerability in the treatment of tuberculosis: A retrospective case review.

    PubMed

    Tse-Chang, Alena; Kunimoto, Dennis; Der, Evelina; Ahmed, Rabia

    2013-01-01

    Linezolid is a potentially effective drug for the treatment of patients with drug-resistant tuberculosis. Among 13 patients treated for tuberculosis with linezolid in the present study, nine had treatment success and four remain on treatment. Adverse effects occurred in 11 (85%) patients, of whom three discontinued treatment because of adverse effects. The present study adds to the growing evidence supporting the efficacy of linezolid for tuberculosis, although treatment remains complicated by adverse effects.

  18. Adverse mucocutaneous reactions related to chemotherapeutic agents: part II.

    PubMed

    Criado, Paulo Ricardo; Brandt, Hebert Roberto Clivati; Moure, Emanuella Rosyane Duarte; Pereira, Guilherme Luiz Stelko; Sanches Júnior, Jose Antonio

    2010-01-01

    Events and reactions involving chemotherapy are common in clinical oncology. Chemotherapeutic agents are widely used in therapy. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from the oncological treatment. The objective of this paper was to present data on skin reactions to chemotherapy, particularly those cases in which the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. The authors describe aspects associated with these events, presenting a detailed analysis of each one of them.

  19. Ginsenoside Rg3 Serves as an Adjuvant Chemotherapeutic Agent and VEGF Inhibitor in the Treatment of Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review

    PubMed Central

    He, Shulin; Hou, Wei

    2016-01-01

    Objective. To evaluate ginsenoside Rg3 combined with chemotherapy for non-small-cell lung cancer (NSCLC) treatment, in a meta-analysis. Materials and Methods. We searched PubMed, EMBASE, the Cochrane Library, the China National Knowledge Infrastructure, and the VIP and Wanfang databases for eligible studies. We manually searched for printed journals and relevant textbooks. Statistical analyses were performed with Revman 5.3 and STATA 14.0 software packages. Results. Twenty studies were included. Ginsenoside Rg3 combined with chemotherapy could enhance response, improve disease control, prolong overall survival, improve patient quality of life, reduce leucocyte count decrease due to chemotherapy, reduce vascular endothelial growth factor expression in peripheral blood, and increase CD4/CD8 T cell ratio. Conclusion. Ginsenoside Rg3 combined with chemotherapy may enhance short-term efficacy and overall survival, alleviate treatment-induced side effects, reduce vascular endothelial growth factor expression, increase CD4/CD8 T cell ratio, and serve as a potential therapeutic regimen for NSCLC. However, considering the limitations, the conclusion should be interpreted carefully, and these results need to be confirmed by more high-quality trials. PMID:27800005

  20. Behavioral Treatment for Marijuana Dependence: Randomized Trial of Contingency Management and Self-Efficacy Enhancement

    PubMed Central

    Litt, Mark D.; Kadden, Ronald M.; Petry, Nancy M.

    2012-01-01

    Objective The purpose of the present study was to develop a treatment for marijuana dependence specifically designed to enhance self-efficacy. Method The participants were 215 marijuana-dependent men and women randomized to one of three 9-week outpatient treatments: a condition intended to enhance self-efficacy through successful completion of treatment-related tasks (Mot ivational Enhancement plus Cognitive-Behavioral treatment plus Contingency Management reinforcing completion of treatment homework; MET+CBT+CMHomework); a condition that controlled for all elements except for reinforcement of homework (MET+CBT + Contingency Management reinforcing drug abstinence ; MET+CBT+CMAbstinence); or a Case Management control condition (CaseM). Participants in the two MET+CBT conditions were also asked to complete interactive voice recordings three times per week during treatment to confirm homework completion. Results All patients showed modest improvements over time through 14 months, with few between-treatment effects on outcomes. Latent Class Growth Models, however, indicated that a subsample of patients did extremely well over time. This subsample was more likely to have been treated in the CMAbstinence condition. In turn, this treatment effects appears to have been accounted for by days of continuous abstinence accrued during treatment, and by pre-post increases in self-efficacy. Conclusions The most effective treatments may be those that elicit abstinence while increasing self-efficacy. PMID:23254227

  1. Chemotherapeutic Approaches for Targeting Cell Death Pathways

    PubMed Central

    Ricci, M. Stacey; Zong, Wei-Xing

    2011-01-01

    For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re-examination of what we know about chemotherapy-induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens. PMID:16614230

  2. Adolescent idiopathic scoliosis: Indications and efficacy of nonoperative treatment

    PubMed Central

    Canavese, Federico; Kaelin, André

    2011-01-01

    The strategy for the treatment of idiopathic scoliosis depends essentially upon the magnitude and pattern of the deformity, and its potential for progression. Treatment options include observation, bracing and/or surgery. During the past decade, several studies have demonstrated that the natural history of adolescent idiopathic scoliosis can be positively affected by nonoperative treatment, especially bracing. Other forms of conservative treatment, such as chiropractic or osteopathic manipulation, acupuncture, exercise or other manual treatments, or diet and nutrition, have not yet been proven to be effective in controlling spinal deformity progression, and those with a natural history that is favorable at the completion of growth. Observation is appropriate treatment for small curves, curves that are at low risk of progression, and those with a natural history that is favorable at the completion of growth. Indications for brace treatment are a growing child presenting with a curve of 25°–40° or a curve less than 25° with documented progression. Curves of 20°–25° in patients with pronounced skeletal immaturity should also be treated. The purpose of this review is to provide information about conservative treatment of adolescent idiopathic scoliosis. Indications for conservative treatment, hours daily wear and complications of brace treatment as well as brace types are discussed. PMID:21221217

  3. Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

    NASA Astrophysics Data System (ADS)

    Roy Chaudhuri, Tista

    An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

  4. Meta-Analysis of Biofeedback for Tension-Type Headache: Efficacy, Specificity, and Treatment Moderators

    ERIC Educational Resources Information Center

    Nestoriuc, Yvonne; Rief, Winfried; Martin, Alexandra

    2008-01-01

    The aims of the present meta-analysis were to investigate the short- and long-term efficacy, multidimensional outcome, and treatment moderators of biofeedback as a behavioral treatment option for tension-type headache. A literature search identified 74 outcome studies, of which 53 were selected according to predefined inclusion criteria.…

  5. Efficacy of mupirocin and rifampin used with standard treatment in the management of acne vulgaris.

    PubMed

    Khorvash, Farzin; Abdi, Fatemeh; H Kashani, Hessam; Fatemi Naeini, Farahnaz; Khorvash, Fariborz

    2013-01-01

    The multiple etiologic factors involved in acne make the use of various medications necessary to treat the condition. This study aimed to determine the efficacy of mupirocin and rifampin used with standard treatment in the management of acne vulgaris. In a multicentre, randomized controlled, triple-blinded study, a total of 105 acne patients, with a clinical diagnosis of moderate to severe acne,were randomizedly divided into three groups (35 per group), for treatment of acne. The first group was treated with standard treatment alone, the second group received mupirocin plus standard treatment and the third group received rifampin plus standard treatment.There were three study visits according to Global Acne Grading System (GAGS): at baseline and weeks 6 and 12. The absolute changes of GAGS score from baseline to week 6 and 12 demonstrated a reduction in the mean score of GAGS in the three treatment groups (p < 0.001). Due to the difference between GAGS score at the baseline of study, the data were adjusted using the general linear model. The findings showed that all of the treatments significantly improved acne lesions. Nevertheless, none of the treatments was shown to be more effective than the others (p = 0.9). The three treatments were well tolerated, and no serious adverse events were reported. These findings provide evidence on the efficacy of combining mupirocin and rifampin with standard treatment in the management of acne vulgaris, although none of the treatments had superior efficacy compared with the others. PMID:24250593

  6. Efficacy of Mupirocin and Rifampin Used with Standard Treatment in the Management of Acne Vulgaris

    PubMed Central

    Khorvash, Farzin; Abdi, Fatemeh; H.Kashani, Hessam; Fatemi Naeini, Farahnaz; Khorvash, Fariborz

    2013-01-01

    The multiple etiologic factors involved in acne make the use of various medications necessary to treat the condition. This study aimed to determine the efficacy of mupirocin and rifampin used with standard treatment in the management of acne vulgaris. In a multicentre, randomized controlled, triple-blinded study, a total of 105 acne patients, with a clinical diagnosis of moderate to severe acne,were randomizedly divided into three groups (35 per group), for treatment of acne. The first group was treated with standard treatment alone, the second group received mupirocin plus standard treatment and the third group received rifampin plus standard treatment.There were three study visits according to Global Acne Grading System (GAGS): at baseline and weeks 6 and 12. The absolute changes of GAGS score from baseline to week 6 and 12 demonstrated a reduction in the mean score of GAGS in the three treatment groups (p < 0.001). Due to the difference between GAGS score at the baseline of study, the data were adjusted using the general linear model. The findings showed that all of the treatments significantly improved acne lesions. Nevertheless, none of the treatments was shown to be more effective than the others (p = 0.9). The three treatments were well tolerated, and no serious adverse events were reported. These findings provide evidence on the efficacy of combining mupirocin and rifampin with standard treatment in the management of acne vulgaris, although none of the treatments had superior efficacy compared with the others. PMID:24250593

  7. Refusers, dropouts, and completers: measuring sex offender treatment efficacy.

    PubMed

    Seager, James A; Jellicoe, Debra; Dhaliwal, Gurmeet K

    2004-10-01

    A sex offender program delivered in a medium-security prison followed 109 treatment completers and 37 noncompleters for 2 years after release. Noncompleters, those who refused treatment or dropped out, had 6 times the rate of sexual and violent reoffending relative to completers. Among those who completed the program, however, positive evaluations of treatment change, such as quality of disclosure and enhanced victim empathy, found in posttreatment assessments did not correlate with recidivism. Furthermore, completers did not differ in their rates of recidivism from pretreatment rates predicted by the Static 99, an actuarial measure of anticipated sexual and violent recidivism. We conclude that the program did not influence propensities for sexual and violent recidivism but rather served as a prolonged screening instrument for sex offenders whose failure to comply with treatment attendance predicted higher rates of recidivism.

  8. Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs.

    PubMed

    Hertz, Everaldo; Cadoná, Francine Carla; Machado, Alencar Kolinski; Azzolin, Verônica; Holmrich, Sabrina; Assmann, Charles; Ledur, Pauline; Ribeiro, Euler Esteves; DE Souza Filho, Olmiro Cezimbra; Mânica-Cattani, Maria Fernanda; DA Cruz, Ivana Beatrice Mânica

    2015-01-01

    Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the treatment of breast cancer. To perform this study, MCF-7 breast cancer cells were cultured under controlled conditions and exposed to 1, 5 and 10 µg/ml guarana concentrations, with and without chemotherapeutics (gemcitabine, vinorelbine, methotrexate, 5-fluorouracil, paclitaxel, doxorubicin and cyclophosphamide). The effect of these treatments on MCF-7 cell viability and proliferation was spectrophotometrically analyzed with the MTT assay. The main results demonstrated an antiproliferative effect of guarana at concentrations of 5 and 10 µg/ml and a significant effect on chemotherapeutic drug action. In general, guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggested an interaction of guarana with the chemotherapeutic drugs, which requires confirmation by in vivo complementary studies. PMID:25469267

  9. Effect of Paullinia cupana on MCF-7 breast cancer cell response to chemotherapeutic drugs.

    PubMed

    Hertz, Everaldo; Cadoná, Francine Carla; Machado, Alencar Kolinski; Azzolin, Verônica; Holmrich, Sabrina; Assmann, Charles; Ledur, Pauline; Ribeiro, Euler Esteves; DE Souza Filho, Olmiro Cezimbra; Mânica-Cattani, Maria Fernanda; DA Cruz, Ivana Beatrice Mânica

    2015-01-01

    Previous studies suggested that certain plants, such as guarana (Paullinia cupana), exert a protective effect against cancer-related fatigue in breast cancer patients undergoing chemotherapy. However, guarana possesses bioactive molecules, such as caffeine and catechin, which may affect the pharmacological properties of antitumor drugs. Therefore, the aim of this study was to evaluate the effects of guarana on breast cancer cell response to 7 chemotherapeutic agents currently used in the treatment of breast cancer. To perform this study, MCF-7 breast cancer cells were cultured under controlled conditions and exposed to 1, 5 and 10 µg/ml guarana concentrations, with and without chemotherapeutics (gemcitabine, vinorelbine, methotrexate, 5-fluorouracil, paclitaxel, doxorubicin and cyclophosphamide). The effect of these treatments on MCF-7 cell viability and proliferation was spectrophotometrically analyzed with the MTT assay. The main results demonstrated an antiproliferative effect of guarana at concentrations of 5 and 10 µg/ml and a significant effect on chemotherapeutic drug action. In general, guarana improved the antiproliferative effect of chemotherapeutic agents, causing a decrease of >40% in cell growth after 72 h of exposure. The results suggested an interaction of guarana with the chemotherapeutic drugs, which requires confirmation by in vivo complementary studies.

  10. Efficacy assessment of local doxycycline treatment in periodontal patients using multivariate chemometric approach.

    PubMed

    Bogdanovska, Liljana; Poceva Panovska, Ana; Nakov, Natalija; Zafirova, Marija; Popovska, Mirjana; Dimitrovska, Aneta; Petkovska, Rumenka

    2016-08-25

    The aim of our study was application of chemometric algorithms for multivariate data analysis in efficacy assessment of the local periodontal treatment with doxycycline (DOX). Treatment efficacy was evaluated by monitoring inflammatory biomarkers in gingival crevicular fluid (GCF) samples and clinical indices before and after the local treatment as well as by determination of DOX concentration in GCF after the local treatment. The experimental values from these determinations were submitted to several chemometric algorithms: principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal projection to latent structures-discriminant analysis (OPLS-DA). The data structure and the mutual relations of the selected variables were thoroughly investigated by PCA. The PLS-DA model identified variables responsible for discrimination of classes of data, before and after DOX treatment. The OPLS-DA model compared the efficacy of the two commonly used medications in periodontal treatment, chlorhexidine (CHX) and DOX, at the same time providing insight in their mechanism of action. The obtained results indicate that application of multivariate chemometric algorithms can be used as a valuable approach for assessment of treatment efficacy. PMID:27283484

  11. Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits.

    PubMed

    Weiss, Shay; Altboum, Zeev; Glinert, Itai; Schlomovitz, Josef; Sittner, Assa; Bar-David, Elad; Kobiler, David; Levy, Haim

    2015-12-01

    Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10(5) CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.

  12. Safety and efficacy of diphetarsone in the treatment of amoebiasis, non-pathogenic amoebiasis and trichuriasis.

    PubMed

    Keystone, J S; Proctor, E; Glenn, C; McIntyre, L

    1983-01-01

    Eighty-nine patients infected with Entamoeba histolytica, non-pathogenic amoebae or Trichuris trichiura were studied prospectively to determine the safety and efficacy of diphetarsone therapy. An additional 75 patients were studied retrospectively to assess further the efficacy of diphetarsone in the treatment of E. histolytica cyst passers. Side effects were noted in 9% and included gastrointestinal upset, lightheadedness and headache. Transient liver function abnormalities were recorded in 5.6%. diphetarsone was completely effective in the treatment of Dientamoeba fragilis, Entamoeba hartmanni, Iodamoeba buetschlii and Trichuris trichiura. 99% of the patients with E. histolytica, 97% of those with E. coli and 98% of those with Endolimax nana were cured. PMID:6304952

  13. Safety and efficacy of incobotulinumtoxinA as a potential treatment for poststroke spasticity

    PubMed Central

    Santamato, Andrea

    2016-01-01

    Spasticity is a common disabling symptom for several neurological conditions. Botulinum toxin type A injection represents the gold standard treatment for focal spasticity after stroke showing efficacy, reversibility, and low prevalence of complications. In recent years, incobotulinumtoxinA, a new Botulinum toxin type A free of complexing proteins, has been used for treating several movement disorders with safety and efficacy. IncobotulinumtoxinA is currently approved for treating spasticity of the upper limb in stroke survivors, even if several studies described the use also in lower limb muscles. In the present review article, we examine the safety and effectiveness of incobotulinumtoxinA for the treatment of spasticity after stroke. PMID:26869793

  14. [Efficacy of antacids in the treatment of chronic gastritis].

    PubMed

    Maev, I V; Dicheva, D T; Lebedeva, E G

    2010-01-01

    This article presents main principles of chronic gastritis treatment. Therapeutic abilities and possible side-effects due to components of antacids are analyzed. Special attention is paid to antisecretory and cytoprotective activity of Pepsan-R, which contains haiasulen (the main active component of chamomilla) and dimeticon. The authors of the article emphasize opportunity of using Pepsan-R in case of heartburn, gastric pain, abdominal distention during pregnancy and lactation.

  15. [Efficacy of antacids in the treatment of chronic gastritis].

    PubMed

    Maev, I V; Dicheva, D T; Lebedeva, E G

    2010-01-01

    This article presents main principles of chronic gastritis treatment. Therapeutic abilities and possible side-effects due to components of antacids are analyzed. Special attention is paid to antisecretory and cytoprotective activity of Pepsan-R, which contains haiasulen (the main active component of chamomilla) and dimeticon. The authors of the article emphasize opportunity of using Pepsan-R in case of heartburn, gastric pain, abdominal distention during pregnancy and lactation. PMID:21434380

  16. [Efficacy of memantine in the treatment of Alzheimer's disease].

    PubMed

    Molinuevo Guix, J L; Lladó Plarrumaní, A

    2005-12-01

    Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by cognitive loss with impairment of daily living activities. The benefits presently observed with the approved treatments are mainly symptomatic without clear evidence of neuroprotection. N-methyl-D-aspartate (NMDA) glutamate receptor antagonists have very extensive therapeutic potential in several central nervous system disorders and can be used in chronic neurodegenerative diseases and in other neurological diseases such as epilepsy. Memantine, a moderate-low affinity, uncompetitive NMDA receptor antagonist, is the only antiglutamatergic drug currently approved for the treatment of moderate to severe AD. Several studies have demonstrated that treatment with memantine has cognitive and functional benefits through all disease stages, while it is safe and well tolerated. Additionally, memantine generates an indirect positive effect on the caregiver, which results in some social benefits. This fact, together with a delay on the transition towards a greater dependence stage is probably associated with a decrease in the number of patients institutionalized. From a socio-economic perspective, these effects mean lower global cost of disease, therefore being a cost-effective drug.

  17. Self-efficacy as a predictor of treatment outcome in adolescent substance use disorders.

    PubMed

    Burleson, Joseph A; Kaminer, Yifrah

    2005-10-01

    Youth substance abuse relapse prevention was examined as a function of patients' situational self-efficacy (SE), their confidence to abstain from substance use in high-risk situations. An increase in SE has been shown to be enhanced by cognitive behavioral therapy (CBT) in adults. Eighty-eight adolescent substance abusers were randomly assigned to either CBT or psycho-education (PET) group therapy. Substance use and SE were assessed at end of treatment, 3- and 9-months after the end of planned treatment. Increased SE predicted subsequent abstinence independently from drug urinalysis and treatment condition only during treatment, while previous substance use predicted subsequent self-efficacy. CBT was not differentially effective than PET in promoting SE. It is recommended that potential mediators and moderators of SE in the treatment of adolescent substance abuse should be further explored. PMID:16095844

  18. Increasing the efficacy of cue exposure treatment in preventing relapse of addictive behavior.

    PubMed

    Havermans, Remco C; Jansen, Anita T M

    2003-07-01

    Theoretically, cue exposure treatment should be able to prevent relapse by extinguishing conditioned drug responding (e.g. cue-elicited craving). According to contemporary learning theory, though, extinction does not eliminate conditioned responding. Analogous cue exposure with response prevention (CERP) as a treatment of addictive behavior might not eliminate the learned relation between drug-related cues and drug use. This does not necessarily mean that cue exposure cannot successfully prevent relapse. Various suggestions for increasing the efficacy of cue exposure treatment are being discussed from a contemporary learning theory perspective. It is suggested that cue exposure treatment incorporating retrieval cues can be a beneficial treatment in preventing relapse of addictive behavior.

  19. Hydromorphone efficacy and treatment protocol impact on tolerance and mu-opioid receptor regulation.

    PubMed

    Kumar, Priyank; Sunkaraneni, Soujanya; Sirohi, Sunil; Dighe, Shveta V; Walker, Ellen A; Yoburn, Byron C

    2008-11-12

    This study examined the antinociceptive (analgesic) efficacy of hydromorphone and hydromorphone-induced tolerance and regulation of mu-opioid receptor density. Initially s.c. hydromorphone's time of peak analgesic (tail-flick) effect (45 min) and ED50 using standard and cumulative dosing protocols (0.22 mg/kg, 0.37 mg/kg, respectively) were determined. The apparent analgesic efficacy (tau) of hydromorphone was then estimated using the operational model of agonism and the irreversible mu-opioid receptor antagonist clocinnamox. Mice were injected with clocinnamox (0.32-25.6 mg/kg, i.p.) and 24 h later, the analgesic potency of hydromorphone was determined. The tau value for hydromorphone was 35, which suggested that hydromorphone is a lower analgesic efficacy opioid agonist. To examine hydromorphone-induced tolerance, mice were continuously infused s.c. with hydromorphone (2.1-31.5 mg/kg/day) for 7 days and then morphine cumulative dose response studies were performed. Other groups of mice were injected with hydromorphone (2.2-22 mg/kg/day) once, or intermittently every 24 h for 7 days. Twenty-four hours after the last injection, mice were tested using morphine cumulative dosing studies. There was more tolerance with infusion treatments compared to intermittent treatment. When compared to higher analgesic efficacy opioids, hydromorphone infusions induced substantially more tolerance. Finally, the effect of chronic infusion (31.5 mg/kg/day) and 7 day intermittent (22 mg/kg/day) hydromorphone treatment on spinal cord mu-opioid receptor density was determined. Hydromorphone did not produce any change in mu-opioid receptor density following either treatment. These results support suggestions that analgesic efficacy is correlated with tolerance magnitude and regulation of mu-opioid receptors when opioid agonists are continuously administered. Taken together, these studies indicate that analgesic efficacy and treatment protocol are important in determining tolerance and

  20. Experimental evaluation of self-efficacy treatment on technical/scientific career outcomes

    NASA Astrophysics Data System (ADS)

    Dawes, Mary Ellen

    Research literature was reviewed concerning the career choices of women, whose talents and abilities continue to be underutilized in many technical and scientific fields. Based on self-efficacy theory, it has been proposed that limited experience results in low self-efficacy beliefs and career interest in technical and scientific fields among women. This study experimentally evaluated a technology education program designed to provide mastery experiences described in self-efficacy theory and predicted to improve career decision making. Seventh and eighth grade students (n=169) were stratified on grade level and randomly assigned either to a published technology education program or to control curricula. Over a 7-week period, the experimental program attempted to foster exploration and performance accomplishments in the students' choice of 3 (out of 21 possible) technical and scientific careers. Pre- and post-test instruments assessed technical/scientific self-efficacy and career interest. No treatment effects were found. However, a demand measure did show significantly greater valuing of the technology education program over the control curricula. It was also noted that students self-selected technology modules for study, and likely selected modules indicating their highest self-efficacy and career interest, which may have limited possible findings. In future research, targeting students with the greatest discrepancy between self-efficacy and performance ability might be more definitive. It should also be noted that the technology education program incorporated elements of self-efficacy theory, but did not include all components. Additional work is necessary to evaluate self-efficacy treatment in career development.

  1. Calpains: Potential Targets for Alternative Chemotherapeutic Intervention Against Human Pathogenic Trypanosomatids

    PubMed Central

    M.H, Branquinha; F.A, Marinho; L.S, Sangenito; S.S.C, Oliveira; K.C, Gonçalves; V, Ennes-Vidal; C.M, d’Avila-Levy; A.L.S, Santos

    2013-01-01

    The treatment for both leishmaniasis and trypanosomiasis, which are severe human infections caused by trypanosomatids belonging to Leishmania and Trypanosoma genera, respectively, is extremely limited because of concerns of toxicity and efficacy with the available anti-protozoan drugs, as well as the emergence of drug resistance. Consequently, the urgency for the discovery of new trypanosomatid targets and novel bioactive compounds is particularly necessary. In this context, the investigation of changes in parasite gene expression between drug resistant/sensitive strains and in the up-regulation of virulence-related genes in infective forms has brought to the fore the involvement of calpain-like proteins in several crucial pathophysiological processes performed by trypanosomatids. These studies were encouraged by the publication of the complete genome sequences of three human pathogenic trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania major, which allowed in silico analyses that in turn directed the identification of numerous genes with interesting chemotherapeutic characteristics, including a large family of calpain-related proteins, in which to date 23 genes were assigned as calpains in T. brucei, 40 in T. cruzi and 33 in L. braziliensis. In the present review, we intend to add to these biochemical/biological reports the investigations performed upon the inhibitory capability of calpain inhibitors against human pathogenic trypanosomatids. PMID:23899207

  2. Statistical approach to measure the efficacy of anthelmintic treatment on horse farms.

    PubMed

    Vidyashankar, A N; Kaplan, R M; Chan, S

    2007-12-01

    Resistance to anthelmintics in gastrointestinal nematodes of livestock is a serious problem and appropriate methods are required to identify and quantify resistance. However, quantification and assessment of resistance depend on an accurate measure of treatment efficacy, and current methodologies fail to properly address the issue. The fecal egg count reduction test (FECRT) is the practical gold standard for measuring anthelmintic efficacy on farms, but these types of data are fraught with high variability that greatly impacts the accuracy of inference on efficacy. This paper develops a statistical model to measure, assess, and evaluate the efficacy of the anthelmintic treatment on horse farms as determined by FECRT. Novel robust bootstrap methods are developed to analyse the data and are compared to other suggested methods in the literature in terms of Type I error and power. The results demonstrate that the bootstrap methods have an optimal Type I error rate and high power to detect differences between the presumed and true efficacy without the need to know the true distribution of pre-treatment egg counts. Finally, data from multiple farms are studied and statistical models developed that take into account between-farm variability. Our analysis establishes that if inter-farm variability is not taken into account, misleading conclusions about resistance can be made.

  3. Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.

    PubMed

    Tomohisa, Mori; Junpei, Ohya; Aki, Masumoto; Masato, Harumiya; Mika, Fukase; Kazumi, Yoshizawa; Teruo, Hayashi; Tsutomu, Suzuki

    2015-11-01

    Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. PMID:26234785

  4. Efficacy of alum for treatment of recurrent aphthous stomatitis

    PubMed Central

    Rafieian, Nasrin; Abdolsamadi, Hamidreza; Moghadamnia, Aliakbar; Jazayeri, Mina; Seif-Rabiee, Mohammadali; Salmanzadeh, Mina; Radi, Shahrbanoo

    2016-01-01

    Background: Recurrent aphthous stomatitis (RAS) is the most common painful ulcers of oral mucosal which can cause many sufferings. Treatment of RAS often includes administration of corticosteroids, analgesics and regulators of the immune system. However, considering the side effects of these medications, even their topical application must be done with caution. Alum is used in traditional medicine for treatment of oral ulcers without significant side effect. This study sought to assess the effect of topical application of alum on aphthous ulcers. Methods: This clinical randomized double-blind placebo-controlled study was conducted on 50 females aged 21 to 27 years. Mucosal adhesive patches were prepared in two forms of basic and 7% alum-containing patches. Subjects in two groups of case and control randomly received the mucosal adhesive patches containing alum and the basic patches, respectively three times in five days. Duration of recovery, changes in size of lesion and severity of pain were recorded. Data were entered into SPSS Version 16 and analyzed using t-test. Results: The average period of full recovery was 7.52 days in the case and 12.2 days in the control groups; which was significantly different (p<0.001). Size of wound and severity of pain were significantly lower at one, three and five days posttreatment compared to baseline values before treatment in the case group (p<0.001) and the difference in this regard between the case and control groups was statistically significant. Conclusion: Alum can significantly decrease the size of aphthous lesions, severity of pain and expedite the recovery of patients with RAS. PMID:27757206

  5. Advances in combination therapies based on nanoparticles for efficacious cancer treatment: an analytical report.

    PubMed

    Mignani, Serge; Bryszewska, Maria; Klajnert-Maculewicz, Barbara; Zablocka, Maria; Majoral, Jean-Pierre

    2015-01-12

    The main objective of nanomedicine research is the development of nanoparticles as drug delivery systems or drugs per se to tackle diseases as cancer, which are a leading cause of death with developed nations. Targeted treatments against solid tumors generally lead to dramatic regressions, but, unfortunately, the responses are often short-lived due to resistant cancer cells. In addition, one of the major challenges of combination drug therapy (called "cocktail") is the crucial optimization of different drug parameters. This issue can be solved using combination nanotherapy. Nanoparticles developed in oncology based on combination nanotherapy are either (a) those designed to combat multidrug resistance or (b) those used to circumvent resistance to clinical cancer drugs. This review provides an overview of the different nanoparticles currently used in clinical treatments in oncology. We analyze in detail the development of combinatorial nanoparticles including dendrimers for dual drug delivery via two strategic approaches: (a) use of chemotherapeutics and chemosensitizers to combat multidrug resistance and (b) use of multiple cytotoxic drugs. Finally, in this review, we discuss the challenges, clinical outlook, and perspectives of the nanoparticle-based combination therapy in cancer.

  6. Levothyroxine Treatment in Pregnancy: Indications, Efficacy, and Therapeutic Regimen

    PubMed Central

    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D.; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3–0.5% and 2–3%, respectively. Thyroid autoantibodies are found in 5–18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy. PMID:21876837

  7. Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic regimen.

    PubMed

    Klubo-Gwiezdzinska, Joanna; Burman, Kenneth D; Van Nostrand, Douglas; Wartofsky, Leonard

    2011-01-01

    The prevalence of overt and subclinical hypothyroidism during pregnancy is estimated to be 0.3-0.5% and 2-3%, respectively. Thyroid autoantibodies are found in 5-18% of women in the childbearing age. The aim of this review is to underscore the clinical significance of these findings on the health of both the mother and her offspring. Methods of evaluation of thyroid function tests (TFTs) during pregnancy are described as are the threshold values for the diagnosis of overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data are provided on potential complications of hypothyroidism/hypothyroxinemia and autoimmune thyroid disease during pregnancy and adverse effects for the offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes and offspring development are discussed with a proposed treatment regimen and follow up strategy.

  8. Comparative efficacy of treatments for pediculosis capitis infestations.

    PubMed

    Meinking, T L; Taplin, D; Kalter, D C; Eberle, M W

    1986-03-01

    Ovicidal activity and killing times were evaluated for six pediculicides, using viable eggs and recently fed head lice from infested children. Lice were continuously exposed to the products until death, and elapsed time was recorded. Eggs were immersed for ten minutes, rinsed, and dried. Four synergized pyrethrin products (RID, R&C Shampoo, A-200 Pyrinate Shampoo, A-200 Pyrinate Liquid) killed all lice in ten to 23 minutes, and 23% to 32% of treated eggs hatched; 0.5% malathion lotion (Prioderm Lotion) killed lice within five minutes and was highly ovicidal, with only 5% of eggs hatching. One percent lindane shampoo (Kwell Shampoo) was the slowest-acting pediculicide, requiring approximately three hours to kill all lice; 30% of the eggs hatched after treatment. The in vitro results for RID, Prioderm Lotion, and K well Shampoo were validated by clinical trials.

  9. Efficacy of proline in the treatment of menopause

    PubMed Central

    Nam, Sun-Young; Yoou, Myoung-Schook

    2016-01-01

    The amino acids in the placenta have multiple functions; however, the therapeutic effects of proline remain poorly for relief postmenopausal symptoms. The aim of present study was to evaluate the effects of proline in the treatment of menopause using in vitro and in vivo models. We assessed the therapeutic effects and regulatory mechanisms of proline by using MCF-7 estrogen-dependent cells, MG63 osteoblast cells, and ovariectomized mice model. An in vivo study was carried out in eight-week-old sham and ovariectomized group. The ovariectomized mouse was further subdivided into two groups administered orally with 17β-estradiol or proline (10 mg/kg/day) for eight weeks. Proline significantly increased cell proliferation and Ki-67 levels in MCF-7 cells and enhanced cell proliferation, alkaline phosphatase activity, extracellular signal-regulated kinase phosphorylation, and glutamyl-prolyl-tRNA synthetase activation in MG63 cells. The estrogen receptor-β and estrogen-response elements luciferase activity were significantly increased by proline in MCF-7 and MG63 cells. In ovariectomized mice, oral administration of proline (10 mg/kg/day) for eight weeks significantly reduced body and vaginal weights. Proline also significantly increased serum estradiol and alkaline phosphatase levels, whereas serum luteinizing hormone was decreased by proline. In addition, detailed microcomputed tomography analysis showed that the proline notably enhanced bone mineral density, trabecular bone volume, and trabecular number in ovariectomized mice. Those findings implied that proline can be a promising candidate for the treatment of menopause. PMID:26830682

  10. Use of cotton rats to evaluate the efficacy of antivirals in treatment of measles virus infections.

    PubMed

    Wyde, P R; Moore-Poveda, D K; De Clercq, E; Neyts, J; Matsuda, A; Minakawa, N; Guzman, E; Gilbert, B E

    2000-05-01

    No practical animal models for the testing of chemotherapeutic or biologic agents identified in cell culture assays as being active against measles virus (MV) are currently available. Cotton rats may serve this purpose. To evaluate this possibility, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and poly(acrylamidomethyl propanesulfonate) (PAMPS), two compounds that have been reported to inhibit MV in vitro, and ribavirin, an established antiviral drug with MV-inhibitory activity, were evaluated for their antiviral activities against MV and respiratory syncytial virus (RSV) in tissue culture and in hispid cotton rats. A single administration of PAMPS markedly inhibited pulmonary RSV or MV replication (>3 log(10) reduction in pulmonary titer compared to that for controls), but only if this compound was administered intranasally at about the time of virus inoculation. Both EICAR and ribavirin exhibited therapeutic activity against RSV and MV in cotton rats when they were administered parenterally. However, both of these compounds were less effective against MV. On the basis of the pulmonary virus titers on day 4 after virus inoculation, the minimal efficacious dose of EICAR against MV (120 mg/kg of body weight/day when delivered intraperitoneally twice daily) appeared to be three times lower against this virus than that of ribavirin delivered at a similar dose (i.e., 360 mg/kg/day). These findings correlated with those obtained in vitro. The data obtained suggest that cotton rats may indeed be useful for the initial evaluation of the activities of antiviral agents against MV.

  11. The Efficacy of Social Skills Treatment for Children with Asperger Syndrome

    ERIC Educational Resources Information Center

    Elder, Lisa M.; Caterino, Linda C.; Chao, Janet; Shaknai, Dina; De Simone, Gina

    2006-01-01

    Children with Asperger Syndrome present with significant social skills deficits, which may contribute to clinical problems such as anxiety, depression, and/or other behavioral disorders. This article provides a description of the nature of Asperger Syndrome and provides possible treatment interventions, specifically focusing on the efficacy of…

  12. Cognitive Restructuring in the Treatment of Social Phobia: Efficacy and Mode of Action.

    ERIC Educational Resources Information Center

    Taylor, Steven; Woody, Sheila; Koch, William J.; McLean, Peter; Paterson, Randy J.; Anderson, Kent W.

    1997-01-01

    Examines whether cognitive restructuring (CR) contributes to treatment efficacy and investigates its mode of action for therapeutic effects. Results, based on 60 persons with generalized social phobia, indicate that CR reduced social phobia and negative social cognitions and increased positive cognitions. CR did not enhance the effects of…

  13. Efficacy and Safety of Immediate-Release Methylphenidate Treatment for Preschoolers with ADHD

    ERIC Educational Resources Information Center

    Greenhill, Laurence; Kollins, Scott; Abikoff, Howard; McCracken, James; Riddle, Mark; Swanson, James; McGough, James; Wigal, Sharon; Wigal, Tim; Vitiello, Benedetto; Skrobala, Anne; Posner, Kelly; Ghuman, Jaswinder; Cunningham, Charles; Davies, Mark; Chuang, Shirley; Cooper, Tom

    2006-01-01

    Objective: The Preschool ADHD Treatment Study (PATS) was a NIMH-funded, six-center, randomized, controlled trial to determine the efficacy and safety of immediate-release methylphenidate (MPH-IR), given t.i.d. to children ages 3 to 5.5 years with attention-deficit/hyperactivity disorder (ADHD). Method: The 8-phase, 70-week PATS protocol included…

  14. Efficacy of Barabasz's Instant Alert Hypnosis in the Treatment of ADHD with Neurotherapy.

    ERIC Educational Resources Information Center

    Anderson, Kathryn; Barabasz, Marianne; Barabasz, Arreed; Warner, Dennis

    2000-01-01

    Tested use of instant alert hypnosis on 16 children diagnosed with attention deficit disorder. Found that EEG beta-theta ratio means were significantly higher in trials of neurotherapy combined with alert hypnosis than neurotherapy alone. Beta was significantly enhanced, whereas theta was inhibited. Identified improved treatment efficacy and…

  15. The Relationship between Relapse Prevention Treatment Outcome and Self-Efficacy.

    ERIC Educational Resources Information Center

    Cantrell, Peggy J.; And Others

    The majority of alcoholics and drug addicts relapse after treatment, with many substance abusers developing a chronic relapse pattern. For this study, 43 patients, who went through a 3-week inpatient relapse prevention program, answered the Situational Confidence Questionnaire (a measure of self-efficacy for alcohol-related, high-risk situations)…

  16. The Mediating Role of Attribution and Self-Efficacy Variables for Treatment Effects on Achievement Outcomes.

    ERIC Educational Resources Information Center

    Relich, Joseph D.; And Others

    1986-01-01

    This experiment explored the mediating functions of attributional and self-efficacy variables on achievement outcomes for skill training treatments offered in conjunction with attributional feedback. Children who were identified as learned helpless and deficient in division skills received training on division operations either through modeling…

  17. [Recommendations of Czech Rheumatological Society for the treatment of rheumatoid arthritis. Efficacy and treatment strategies].

    PubMed

    Becvár, R; Vencovský, J; Nĕmec, P; Suchý, D; Procházková, L; Pavelka, K

    2008-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease of unknown aetiology characterized by presence of chronic symmetric synovitis, which leads to the formation of joint erosions. Generally recommended method for activity assessment of RA is so called Disease Activity Score (DAS). In early RA when low disease activity is present with oligo- or monoarthritis antimalarials are drugs of choice, while sulfasalazine (SAS) is recommended in cases with medium activity without erosions. Initial treatment with methotrexate (MTX) or leflunomide (LEF) should be applied in a very active polyarthritis with a rapid development of erosions. MTX is often combined with other disease modifying drugs (DMARD) and the blockers of tumour necrosis factor alpha (TNF-alpha). LEF is to be administered to the patients in whom the other DMARD are contraindicated or not tolerated. In established RA with oligo- or monoarthritis with permanent low activity SAS is DMARD of choice. In cases with insufficient response and medium activity MTX is used and if it is inefficient LEF or combination of DMARD should be considered. In a very active disease with a rapid evolution of erosions high doses of MTX or LEF are recommended. When extraarticular symptoms of RA are present azathioprine is to be applied and in case of involvement of vital organs cyclophosphamide should be used. When DMARD are failing or contraindicated TNF-alpha blockers are to be applied. When one TNF-alpha blocker is inefficient it should by replaced by another one from the same group or another biological should be used. For indication of biologicals the activity limit is DAS28 5.1 and the decrease of DAS28 more than 1.2 is an efficacy criterion. Nonsteroidal antirheumatic drugs are an important part in the management of RA, and also corticosteroids are often of used in oral or parenteral form. To the complex therapy of RA nonpharmacological means are usually implemented--different physical procedures and various surgeries. PMID

  18. The Efficacy of Steroid Injection in the Treatment of Trigger Finger

    PubMed Central

    Nakhdjevani, Amir; Lloyd, Mary A.; Schreuder, Frederik B.

    2012-01-01

    Background Trigger finger is one of the most common reasons for referral to a hand specialist clinic. The purpose of this study is to investigate the efficacy of steroid injections for treating trigger digits. Methods Ninety digits were investigated with at least a year follow up. The study mainly focused on the efficacy of the injections, as well as co-morbidities, presence of a nodule, actual digit injected and the severity at presentation using Green's classification. Results The study found that 66% of trigger digits were effectively treated using steroid injections. There was a difference between the efficacy of the injection in the different digits, with a statistical significance between the thumb and the fingers. The results also showed that there was no statistical relationship between the severity of the condition, the presence of a nodule or co-morbidities and the efficacy of the steroid injections. Conclusions The study found that steroid injections are an effective first-line intervention for the treatment of trigger digit. It also found an increased efficacy for treating the thumb compared to other digits. Both the severity of the condition at presentation and the presence of a nodule had no significant impact on the efficacy of the injections. PMID:23205235

  19. [ULTRASOUND CRITERIA OR THE OPERABILITY AND EFFICACY OF THE TREATMENT OF THE MALIGNANT EPITHELIAL OVARIAN TUMOURS].

    PubMed

    Shkarbun, K D; Shkarbun, L I

    2015-01-01

    In order to isolate the main sonographic criteria of ovarian cancer operability the dynamical U.S. examination was performed on 65 women with epithelial tumors of II-III stages before and during 5 years after treatment beginning, which included (in different combinations) cytoreductive surgery and neoadjuvant chemotherapy. Only total 14 (21.5%) relapses were revealed. The U.S. prognostic criteria of the ovarian cancer treatment efficacy with and without neoadjuvant chemotherapy were defined. PMID:27491160

  20. The Efficacy of Radiotherapy in the Treatment of Orbital Pseudotumor

    SciTech Connect

    Matthiesen, Chance; Bogardus, Carl; Thompson, J. Spencer; Farris, Bradley; Hildebrand, Lloyd; Wilkes, Byron; Syzek, Elizabeth; Algan, Ozer; Ahmad, Salahuddin; Herman, Terence

    2011-04-01

    Purpose: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor. Methods and Materials: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months. Results: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement of preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients. Conclusions: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response.

  1. The efficacy and tolerability of bupropion in the treatment of major depressive disorder.

    PubMed

    Moreira, Ricardo

    2011-10-19

    Major depressive disorder (MDD) is a highly recurrent condition associated with a substantial burden of disease. Antidepressants alone or in combination with psychotherapy are the mainstay of treatment. Evidence demonstrates that antidepressant agents are significantly more efficacious than placebo in treating MDD, and antidepressants of different types have similar efficacies. However, not all patients respond to initial pharmacological treatment, suggesting the need for antidepressants with different mechanisms of action. Bupropion is a second-generation antidepressant, with a mechanism of action different from most antidepressants, in that it is a dopamine and norepinephrine reuptake inhibitor. Bupropion has demonstrated efficacy in the treatment of MDD, measured by Hamilton depression rating scale total and clinical global impressions severity and improvement scores, the proportion of responders, the proportion of patients in remission of disease, the prevention of relapse and beneficial effect on a range of health-related quality of life measures. With an efficacy that is at least similar to most other common antidepressants, including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors and other second-generation drugs, bupropion has a favourable acceptability and tolerability profile. In particular, it has a minimal effect on sexual function, comparable or lower rates of somnolence than placebo, and is associated with lower rates of weight gain and sedation than some other commonly used antidepressants. Combination therapy of bupropion with other second-generation antidepressants has been shown to improve outcomes in patients failing antidepressant monotherapy. Bupropion is approved for the treatment of MDD in the USA, Canada and many countries in Europe, and current evidence-based guidelines reinforce its place as an efficacious and well-tolerated treatment option in the pharmacological management of MDD.

  2. Quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapeutic agents.

    PubMed

    Wang, Wenge; Gallant, Jean-Nicolas; Katz, Sharyn I; Dolloff, Nathan G; Smith, Charles D; Abdulghani, Junaid; Allen, Joshua E; Dicker, David T; Hong, Bo; Navaraj, Arunasalam; El-Deiry, Wafik S

    2011-08-01

    Quinacrine has been widely explored in treatment of malaria, giardiasis, and rheumatic diseases. We find that quinacrine stabilizes p53 and induces p53-dependent and independent cell death. Treatment by quinacrine alone at concentrations of 10-20 mM for 1-2 d cannot kill hepatocellular carcinoma cells, such as HepG2, Hep3B, Huh7, which are also resistant to TRAIL. However, quinacrine renders these cells sensitive to treatment by TRAIL. Co-treatment of these cells with quinacrine and TRAIL induces overwhelming cell death within 3-4 h. Levels of DR5, a pro-apoptotic death receptor of TRAIL, are increased upon treatment with quinacrine, while levels of Mcl-1, an anti-apoptotic member of the Bcl-2 family, are decreased. While the synergistic effect of quinacrine with TRAIL appears to be in part independent of p53, knockdown of p53 in HepG2 cells by siRNA results in more cell death after treatment by quinacrine and TRAIL. The mechanism by which quinacrine sensitizes hepatocellular carcinoma cells to TRAIL and chemotherapies, and the potential for clinical application currently are being further explored. Lastly, quinacrine synergizes with chemotherapeutics, such as adriamycin, 5-FU, etoposide, CPT11, sorafenib, and gemcitabine, in killing hepatocellular carcinoma cells in vitro and the drug enhances the activity of sorafenib to delay tumor growth in vivo. PMID:21725212

  3. Efficacy of chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in Honduras.

    PubMed

    Mejia Torres, Rosa Elena; Banegas, Engels Ilich; Mendoza, Meisy; Diaz, Cesar; Bucheli, Sandra Tamara Mancero; Fontecha, Gustavo A; Alam, Md Tauqeer; Goldman, Ira; Udhayakumar, Venkatachalam; Zambrano, Jose Orlinder Nicolas

    2013-05-01

    Chloroquine (CQ) is officially used for the primary treatment of Plasmodium falciparum malaria in Honduras. In this study, the therapeutic efficacy of CQ for the treatment of uncomplicated P. falciparum malaria in the municipality of Puerto Lempira, Gracias a Dios, Honduras was evaluated using the Pan American Health Organization-World Health Organization protocol with a follow-up of 28 days. Sixty-eight patients from 6 months to 60 years of age microscopically diagnosed with uncomplicated P. falciparum malaria were included in the final analysis. All patients who were treated with CQ (25 mg/kg over 3 days) cleared parasitemia by day 3 and acquired no new P. falciparum infection within 28 days of follow-up. All the parasite samples sequenced for CQ resistance mutations (pfcrt) showed only the CQ-sensitive genotype (CVMNK). This finding shows that CQ remains highly efficacious for the treatment of uncomplicated P. falciparum malaria in Gracias a Dios, Honduras.

  4. Efficacy of MTA and CEM Cement with Collagen Membranes for Treatment of Class II Furcation Defects

    PubMed Central

    Ghanbari, Habib Ollah; Taheri, Morteza; Abolfazli, Salman; Asgary, Saeed; Gharechahi, Maryam

    2014-01-01

    Objectives: This study aimed to compare the efficacy of MTA and CEM cement in Class II furcation defects in human mandibular molars. Materials and Methods: Forty furcation defects were treated in 16 patients with chronic periodontitis. The clinical parameters of probing depth (PD), vertical and horizontal clinical attachment levels (VCAL and HCAL), open vertical and horizontal furcation depths (OVFD and OHFD), and gingival margin level (GML) were measured at baseline and at 3- and 6-month (re-entry surgery) postoperatively. Data were analyzed at a significance level of P<0.05. Results: Use of MTA and CEM caused significant decreases in PD, VCAL, HCAL, OVFD and OHFD at re-entry, with no statistically significant differences between the two treatment options in soft and hard tissue parameters. Conclusion: Both treatment modalities caused significant gains in attachment levels and bone fills, proving efficacy for treatment of Class II furcation involvements. PMID:25628670

  5. Efficacy of high frequency ultrasound in postoperative evaluation of carpal tunnel syndrome treatment

    PubMed Central

    Urbanik, Andrzej

    2016-01-01

    Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and a frequent cause of sick leave because of work-related hand overload. The main treatment is operation. Aim The aim of the study is to assess the usefulness of high frequency ultrasound in the postoperative evaluation of CTS treatment efficacy. Material and methods Sixty-two patients (50 women and 12 men aged 28–70, mean age 55.2) underwent surgical treatment of CTS. Ultrasound examinations of the wrist in all carpal tunnel sufferers were performed 3 months after the procedure with the use of a high frequency broadband linear array transducer (6–18 MHz, using 18 MHz band) of MyLab 70/Esaote. On the basis of the collected data, the author has performed multiple analyses to confirm the usefulness of ultrasound imaging for postoperative evaluation of CTS treatment efficacy. Results Among all 62 patients, 3 months after surgical median nerve decompression: in 40 patients, CTS symptoms subsided completely, and sonographic evaluation did not show median nerve entrapment signs; in 9 patients, CTS symptoms persisted or exacerbated, and ultrasound proved nerve compression revealing preserved flexor retinaculum fibers; in 13 patients, scar tissue symptoms occurred, and in 5 of them CTS did not subside completely (although ultrasound showed no signs of compression). Conclusions Ultrasound imaging with the use of a high frequency transducer is a valuable diagnostic tool for postoperative assessment of CTS treatment efficacy. PMID:27103999

  6. Therapeutic Efficacy and Macrofilaricidal Activity of Doxycycline for the Treatment of River Blindness

    PubMed Central

    Walker, Martin; Specht, Sabine; Churcher, Thomas S.; Hoerauf, Achim; Taylor, Mark J.; Basáñez, María-Gloria

    2015-01-01

    Background. Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. Methods. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. Results. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%–94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%–80%, from approximately 10 years to 2–3 years. Conclusions. The efficacy parameters are pertinent to the prospects of using doxycycline on a “test and treat” basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings. PMID:25537873

  7. Efficacy of ozone and other treatment modalities for retained placenta in dairy cows.

    PubMed

    Zobel, R; Tkalčić, S

    2013-02-01

    Retained placenta is a worldwide recognized clinical condition in puerperal cows, which can significantly affect their health and fertility. Available treatment modalities are often of questionable efficacy or associated with time constraints, practicality or monetary considerations for their wide application in a routine dairy practice. The objective of this study was to compare and assess the efficacy of different treatment options, including a novel ozone treatment, for the retained placenta. Two hundred cows diagnosed with retained placenta were divided into five treatment groups, each receiving a different treatment option. Group A (n = 40) was given a combination treatment of intrauterine ozone and parenteral cephalexin; group B (n = 40) was given intrauterine ozone; group C (n = 40) was given a combination of parenteral cephalexin and intrauterine antibiotic tablets; group D (n = 40) was given only parenteral cephalexin and group E (n = 40) was given parenteral prostaglandins in 11-day intervals. The control group (group Z, n = 200) included cows that gave birth without assistance and were not diagnosed with a retained placenta. The ozone treatment (groups A and B) was found to be the most effective modality resulting in the shortest period of days open, the smallest number of artificial inseminations until pregnancy, the smallest number of animals diagnosed with fever within 10 days post-calving, the highest percentage of animals pregnant within 200 days after calving and the smallest number of animals culled because of infertility, when compared to the other treatment groups. The intrauterine ozone flush therefore has a potential as an efficacious and cost-effective treatment option for retained placenta, with an overall positive effect on puerperal health and fertility in cows.

  8. Efficacy of leflunomide for treatment of refractory inflammatory colorectal polyps in 15 Miniature Dachshunds

    PubMed Central

    FUKUSHIMA, Kenjiro; EGUCHI, Nozomi; OHNO, Koichi; KANEMOTO, Hideyuki; TAKAHASHI, Masashi; IGARASHI, Hirotaka; OHMI, Aki; NAKASHIMA, Ko; TSUJIMOTO, Hajime

    2015-01-01

    Inflammatory colorectal polyp (ICRP), common in miniature dachshunds, presents with hematochezia, tenesmus and mucoid feces. Although an 80% response rate has been reported when treated with prednisolone and cyclosporine, effective treatment is needed for the remaining 20% of ICRP dogs. Leflunomide is an immunosuppressive drug reported as effective in several immune-mediated diseases. In the present study, we retrospectively evaluated the efficacy and adverse effects of leflunomide in 15 ICRP dogs that were refractory to treatment with prednisolone and cyclosporine. Treatment efficacy was assessed by endoscopy, clinical symptoms and rectal palpation. Adverse effects were determined by clinical symptoms and blood testing during follow-up. The leflunomide treatment response rate was 93.3%. The median dosage of leflunomide and the median response time were 3 mg/kg (range: 1.7–4.0 mg/kg) and 35 days (range: 20–119 days), respectively. Adverse effects observed included lethargy (3 dogs), anorexia (1 dog), respiratory symptoms (1 dog), leukocytopenia (2 dogs), thrombocytopenia (1 dog), anemia (1 dog) and liver enzyme elevation (8 dogs). Most of the adverse effects improved with symptomatic treatment and leflunomide discontinuation or dosage reduction. In conclusion, leflunomide treatment is effective in ICRP dogs refractory to treatment with prednisolone and cyclosporine. Because several adverse effects were observed, close monitoring is needed during leflunomide treatment follow-up. PMID:26460312

  9. Efficacy of 5-Nitroimidazoles for the Treatment of Giardiasis: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Deshpande, Abhishek; Thota, Priyaleela; Roman, Yuani; Hernandez, Adrian V.

    2014-01-01

    Background Giardiasis is one of the most common causes of diarrheal disease worldwide and 5-nitroimidazoles (5-NI) are the most commonly prescribed drugs for the treatment of giardiasis. We evaluated the efficacy of 5-nitroimidazoles (5-NI) in the treatment of giardiasis in a systematic review of randomized controlled trials (RCTs). Methodology/Principal Findings We conducted a comprehensive literature search in PubMed-Medline, Scopus, Web of Science and Cochrane Library for RCTs evaluating the efficacy of 5-NI vs. control (placebo or active treatment) on parasitological cure in patients with parasitologically-demonstrated giardiasis. The search was performed in May 2013 with no language restriction by two authors independently. The efficacy outcome was parasitological cure, and harmful outcomes were abdominal pain, bitter or metallic taste, and headache. We included 30 RCTs (n = 3,930). There was a significant and slightly higher response rate with 5-NI in giardiasis treatment (RR 1.06, 95%CI 1.02–1.11, p = 0.005). There was high heterogeneity among studies (I2 = 72%). The response rates for metronidazole, tinidazole and secnidazole were similar (RR 1.05, 95%CI 1.01–1.09, p = 0.01; RR 1.32 95%CI 1.10–1.59, p = 0.003; and RR 1.18 95%CI 0.93–1.449, p = 0.18, respectively). On subgroup analyses, the response rates did not vary substantially and high heterogeneity persisted (I2 = 57%–80%). Harmful outcomes were uncommon, and 5-NIs were associated with lower risk of abdominal pain, and higher risk of both bitter or metallic taste and headache. Conclusions Studies investigating the efficacy of 5-NI in giardiasis treatment are highly heterogeneous. 5-NIs have a slightly better efficacy and worse profile for mild harmful outcomes in the treatment of giardiasis in comparison to controls. Larger high quality RCTs are needed to further assess efficacy and safety profiles of 5-NI. PMID:24625554

  10. Muscle biofeedback and transcendental meditation. A controlled evaluation of efficacy in the treatment of chronic anxiety.

    PubMed

    Raskin, M; Bali, L R; Peeke, H V

    1980-01-01

    Recent articles have suggested that muscle biofeedback and transcendental meditation may be useful in treating chronic anxiety. To assess this, we conducted a controlled study comparing muscle biofeedback, transcendental mediation, and relaxation therapy. The study consisted of a six-week baseline period, six weeks of treatment, a six-week posttreatment observation period, and later follow-up. Thirty-one subjects completed the first part of the study and have been followed up for three to 18 months. Forty percent of the subjects had a clinically significant decrease in their anxiety. There were no differences between treatments with respect to treatment efficacy, onset of symptom amelioration, or maintenance of therapeutic gains. We found no evidence suggesting that the degree of muscle relaxation induced by any of the treatments is related to the therapeutic outcome. Relaxation therapies as a sole treatment appear to have a limited place in the treatment of chronic anxiety.

  11. Hyperbaric oxygen in the treatment of osteoradionecrosis: a review of its use and efficacy

    SciTech Connect

    Fattore, L.; Strauss, R.A.

    1987-03-01

    Hyperbaric oxygen (HBO) therapy is an established technology that is proving to be effective in the treatment of osteoradionecrosis. However, the studies that have shown this treatment modality to be effective have not established the optimum pressures, times of exposure, and frequency and number of treatment necessary for healing. In addition, most of the studies used HBO as an adjunctive treatment in the management of refractory osteoradionecrosis. The efficacy of HBO as a primary treatment modality has not as yet been established. Strictly controlled clinical trials are necessary for identification of patients who are likely to respond to HBO without aggressive surgery, to delineate a timetable for treatment of patients with HBO, and to coordinate surgery with HBO to resolve osteoradionecrosis when a significant amount of bone loss is involved.

  12. THE STUDY OF EFFICACY OF FAMILY WARD TREATMENT IN HYSTERIA IN COMPARISON WITH THE OPEN WARD AND THE OUTPATIENT TREATMENT

    PubMed Central

    Geetha, P. R.; Channabasavanna, S. M.; Bhatti, Ranbir S.

    1980-01-01

    SUMMARY A comparative study of the efficacy of treatment of hysterical patients is made among three group of patients—patients treated in family wards, open wards and out-patients. The number of patients is fifteen in each group and they are matched for age, sex, per capita income, duration of illness and type of illness. Significant differences among three groups on certain parameters like personality have been eliminated. The results are discussed. PMID:22058491

  13. Factors affecting treatment efficacy in social phobia: the use of video feedback and individual vs. group formats.

    PubMed

    Aderka, Idan M

    2009-01-01

    This meta-analysis assessed two potential moderators of treatment efficacy in social phobia: video feedback, and treatment format (i.e., individual vs. group). Eighteen recent (2000-2006) trials including a total of 511 participants were sampled. Effect sizes (Cohen's d's) were calculated for each trial while correcting for measurement error. The Q statistic was used to test (a) heterogeneity across trials and (b) potential moderators. Results indicated that use of video feedback was not a moderator of treatment efficacy and did not significantly affect effect sizes. In contrast, treatment format was a moderator of treatment efficacy such that individual treatments reported larger effect sizes and lower attrition rates compared with group treatments. The results suggest that individual treatments in social phobia may be superior to group treatments irrespective of treatment type. PMID:18599263

  14. Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

    PubMed

    Abdel-Raheem, Talal A; Méabed, Eman M H; Nasef, Ghada A; Abdel Wahed, Wafaa Y; Rohaim, Rania M A

    2016-10-01

    The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 μg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient.

  15. Efficacy, acceptability and cost effectiveness of four therapeutic agents for treatment of scabies.

    PubMed

    Abdel-Raheem, Talal A; Méabed, Eman M H; Nasef, Ghada A; Abdel Wahed, Wafaa Y; Rohaim, Rania M A

    2016-10-01

    The aim of this study is to evaluate four drug regimens for treatment of scabies as regard their efficacy, acceptability and cost effectiveness. Two hundred cases with ordinary scabies were randomized into four groups. First group received ivermectin 200 μg/kg body weight single oral dose, repeated after one week. The second received benzyl benzoate 20% cream. The third received permethrin 2.5%-5% lotion, whereas the fourth group received 5-10% sulfur ointment. Topical treatments were applied for five consecutive nights. Patients were followed up for two weeks for cure rate and adverse effects. At the end of the study, permethrin provided a significant efficacy of 88% and acceptability in 100% of cases, but had higher cost to treat one case (20.25 LE). Ivermectin provided efficacy and acceptability rates of 84% and 96%, respectively, and had a cheaper cost (9.5 LE). Benzyl benzoate provided 80% for both rates and was the cheapest drug. Sulfur ointment provided the least rates, and it was the most expensive. Treatment choice will depend on the age, the general condition of cases, patient compliance to topical treatment and his ability to stick to its roles, and the economic condition of the patient. PMID:27027929

  16. Clinical efficacy of a new ciclopiroxolamine/zinc pyrithione shampoo in scalp seborrheic dermatitis treatment.

    PubMed

    Lorette, Gérard; Ermosilla, Valérie

    2006-01-01

    Ciclopiroxolamine (CPO) and Zinc Pirythione (ZP) antifungals are efficient at treating scalp seborrheic dermatitis. This multicentre, single-blind, clinical study was conducted to evaluate the efficacy of a shampoo containing the 1.5% CPO/1% ZP association compared to the vehicle shampoo and to 2% ketoconazole foaming gel in the treatment of seborrheic dermatitis. In 189 patients randomised to apply 1 of the 3 products twice a week for 28 days, the global lesional score, erythema, pruritus, global efficacy, quality of life (SF12 and DLQI questionnaires) and tolerance were measured at 0, 7, 14 and 28 days. The 3 products reduced lesional score, erythema and pruritus from day 7 (p < 0.0001). The 2 antifungal treatments were significantly more efficient than the vehicle in reducing lesional score, erythema and pruritus at day 14 (p < 0.0001). At day 7, the CPO/ZP shampoo was more efficient in reducing pruritus than ketoconazole gel and vehicle (p = 0.032 and p < 0.001, respectively). The global efficacy of the 2 antifungal treatments assessed at day 28 by both investigator and patient was significantly better than that of the vehicle. Only the CPO/ZP shampoo improved all DLQI questionnaire dimensions. The CPO/ZP shampoo was as rapid and efficient as ketoconazole gel in SD treatment.

  17. Is rehospitalization a measure of the efficacy of neuroleptics in the treatment of schizophrenia?

    PubMed

    Bourin, M; Jolliet, P; Hery, P; Guitton, B

    1998-01-01

    This study was undertaken to evaluate the efficacy of standard neuroleptic treatment versus depot neuroleptic treatment. The major criterion for evaluation was the number of patients hospitalized. Patients were chosen on the basis of their rating by the ICD-10 classification for schizophrenic disorders. The first study period was defined as the time when patients were treated with standard neuroleptics; the second was when patients were treated with depot neuroleptics. There were 231 hospitalizations during the first period, which involved 48 patients, i.e. 4.8 hospitalizations per patient. The mean total duration of these hospitalizations was 5.2 years, i.e. it was on average 5 years before the patient was treated with a depot neuroleptic, with 0.93 hospitalizations per year. The duration of the second period was the same as the first. Only 44 patients remained in the study during this period; their mean number of hospitalizations was 7.2 per patient. The mean number of hospitalizations per year per patient was 1.25. The results suggest that the number of hospitalizations is only a partially satisfactory way of evaluating the efficacy of neuroleptic treatments, and questions the relative efficacy of depot neuroleptics compared with standard neuroleptic treatment.

  18. Safety and Efficacy of Filtered Sunlight in Treatment of Jaundice in African Neonates

    PubMed Central

    Vreman, Hendrik J.; Olusanya, Bolajoko O.; Wong, Ronald J.; Brearley, Ann M.; Vaucher, Yvonne E.; Stevenson, David K.

    2014-01-01

    OBJECTIVES: Evaluate safety and efficacy of filtered-sunlight phototherapy (FS-PT). METHODS: Term/late preterm infants ≤14 days old with clinically significant jaundice, assessed by total bilirubin (TB) levels, were recruited from a maternity hospital in Lagos, Nigeria. Sunlight was filtered with commercial window-tinting films that remove most UV and significant levels of infrared light and transmit effective levels of therapeutic blue light. After placing infants under an FS-PT canopy, hourly measurements of axillary temperatures, monitoring for sunburn, dehydration, and irradiances of filtered sunlight were performed. Treatment was deemed safe and efficacious if infants were able to stay in FS-PT for ≥5 hours and rate of rise of TB was <0.2 mg/dL/h for infants ≤72 hours of age or TB decreased for infants >72 hours of age. RESULTS: A total of 227 infants received 258 days of FS-PT. No infant developed sunburn or dehydration. On 85 (33%) of 258 treatment days, infants were removed briefly from FS-PT due to minor temperature-related adverse events. No infant met study exit criteria. FS-PT was efficacious in 92% (181/197) of evaluable treatment days. Mean ± SD TB change was –0.06 ± 0.19 mg/dL/h. The mean ± SD (range) irradiance of FS-PT was 38 ± 22 (2–115) µW/cm2/nm, measured by the BiliBlanket Meter II. CONCLUSIONS: With appropriate monitoring, filtered sunlight is a novel, practical, and inexpensive method of PT that potentially offers safe and efficacious treatment strategy for management of neonatal jaundice in tropical countries where conventional PT treatment is not available. PMID:24864170

  19. Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis

    PubMed Central

    Lyu, Xin; Zhao, Chen; Yan, Zhi-min; Hua, Hong

    2016-01-01

    Objective To systematically review and assess the efficacy, different treatment protocols (formulation, dosage, and duration), and safety of nystatin for treating oral candidiasis. Methods Four electronic databases were searched for trials published in English till July 1, 2015. Randomized controlled trials comparing nystatin with other antifungal therapies or a placebo were included. Clinical and/or mycological cure was the outcome evaluation. A meta-analysis or descriptive study on the efficacy, treatment protocols, and safety of nystatin was conducted. Results The meta-analysis showed that nystatin pastille was significantly superior to placebo in treating denture stomatitis. Nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. The descriptive investigations showed that administration of nystatin suspension and pastilles in combination for 2 weeks might achieve a higher clinical and mycological cure rate, and using the nystatin pastilles alone might have a higher mycological cure rate, when compared with using nystatin suspensions alone. Nystatin pastilles at a dose of 400,000 IU resulted in a significantly higher mycological cure rate than that administrated at a dose of 200,000 IU. Furthermore, treatment with nystatin pastilles for 4 weeks seemed to have better clinical efficacy than treatment for 2 weeks. Descriptive safety assessment showed that poor taste and gastrointestinal adverse reaction are the most common adverse effects of nystatin. Conclusion Nystatin pastille was significantly superior to placebo in treating denture stomatitis, while nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. Indirect evidence from a descriptive study demonstrated that administration of nystatin pastille alone or pastille and suspension in combination is more effective than that of suspension alone; prolonged treatment duration

  20. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis.

    PubMed

    Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

    2013-01-01

    To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn's disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept

  1. Long-term safety and efficacy of etanercept in the treatment of ankylosing spondylitis

    PubMed Central

    Senabre-Gallego, José Miguel; Santos-Ramírez, Carlos; Santos-Soler, Gregorio; Salas-Heredia, Esteban; Sánchez-Barrioluengo, Mabel; Barber, Xavier; Rosas, José

    2013-01-01

    To date, anti-tumor necrosis factor alfa (anti-TNF-α) therapy is the only alternative to nonsteroidal anti-inflammatory drugs for the treatment of ankylosing spondylitis. Etanercept is a soluble TNF receptor, with a mode of action and pharmacokinetics different to those of antibodies and distinctive efficacy and safety. Etanercept has demonstrated efficacy in the treatment of ankylosing spondylitis, with or without radiographic sacroiliitis, and other manifestations of the disease, including peripheral arthritis, enthesitis, and psoriasis. Etanercept is not efficacious in inflammatory bowel disease, and its efficacy in the treatment of uveitis appears to be lower than that of other anti-TNF drugs. Studies of etanercept confirmed regression of bone edema on magnetic resonance imaging of the spine and sacroiliac joint, but failed to reduce radiographic progression, as do the other anti-TNF drugs. It seems that a proportion of patients remain in disease remission when the etanercept dose is reduced or administration intervals are extended. Etanercept is generally well tolerated with an acceptable safety profile in the treatment of ankylosing spondylitis. The most common adverse effect of etanercept treatment is injection site reactions, which are generally self-limiting. Reactivation of tuberculosis, reactivation of hepatitis B virus infection, congestive heart failure, demyelinating neurologic disorders, hematologic disorders like aplastic anemia and pancytopenia, vasculitis, immunogenicity, and exacerbation or induction of psoriasis are class effects of all the anti-TNF drugs, and have been seen in patients with ankylosing spondylitis. However, etanercept is less likely to induce reactivation of tuberculosis than the other anti-TNF drugs and it has been suggested that etanercept might be less immunogenic, especially in ankylosing spondylitis. Acute uveitis, Crohn’s disease, and sarcoidosis are other adverse events that have been rarely associated with etanercept

  2. Stopwatch-assessed duration of erection: a new measure of the efficacy of erectile dysfunction treatments.

    PubMed

    Rosenberg, M T; Miner, M M; Barnes, A L; Janning, S W

    2011-01-01

    Results are reported from the first two adequate trials of the PDE-5 inhibitor vardenafil using a stopwatch to precisely measure erection duration in men with ED. Two randomized, multicenter, double-blind, placebo-controlled trials were conducted: a crossover 4-week treatment in men with ED (ENDURANCE) and a parallel group, 12-week treatment in men with ED and dyslipidemia (the dyslipidemia study). Stopwatch-assessed duration of erection leading to successful intercourse measured by Sexual Encounter Profile question-3 (SEP-3) was the primary end point in ENDURANCE and one of the secondary end points in the dyslipidemia study. Other efficacy end points included responses to SEP-2, SEP-3 and International Index of Erectile Function-Erectile Function (IIEF-EF) domain scores. Adverse events were recorded. Duration of erection (least squares mean ± s.e.) leading to successful intercourse was statistically superior in men receiving vardenafil versus placebo (12.8 ± 1.0 versus 5.5 ± 1.0 min; p<0.001 in ENDURANCE and 10.0 ± 0.8 versus 3.4 ± 0.8; p<0.001 in the dyslipidemia study), with a difference of 7.4 and 6.6 min, respectively, between treatment groups. Results for SEP-2, SEP-3 and IIEF-EF domain scores were consistent across studies and with stopwatch-assessed measures for duration of erection. Vardenafil was well tolerated. Duration of erection leading to successful intercourse is an important indicator of the efficacy of ED treatment. The stopwatch approach offers an alternative, precise and reproducible measure of efficacy. We propose this approach as a potential new paradigm for assessing the efficacy of ED treatments.

  3. End-of-treatment abstinence self-efficacy, behavioral processes of change, and posttreatment drinking outcomes in Project MATCH.

    PubMed

    Crouch, Taylor Berens; DiClemente, Carlo C; Pitts, Steven C

    2015-09-01

    This study evaluated whether alcohol abstinence self-efficacy at the end of alcohol treatment was moderated by utilization of behavioral processes of change (coping activities used during a behavior change attempt). It was hypothesized that self-efficacy would be differentially important in predicting posttreatment drinking outcomes depending on the level of behavioral processes, such that the relation between self-efficacy and outcomes would be stronger for individuals who reported low process use. Analyses were also estimated with end-of-treatment abstinence included as a covariate. Data were analyzed from alcohol-dependent individuals in both treatment arms of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity; N = 1,328), a large alcohol treatment study. Self-efficacy was moderated by behavioral process use in predicting drinking frequency 6 and 12 months posttreatment and drinking quantity 6 months posttreatment such that self-efficacy was more strongly related to posttreatment drinking when low levels of processes were reported than high levels, but interactions were attenuated when end-of-treatment abstinence was controlled for. Significant quadratic relations between end-of-treatment self-efficacy and 6- and 12-month posttreatment drinking quantity and frequency were found (p < .001, ƒ² = 0.02-0.03), such that self-efficacy most robustly predicted outcomes when high. These effects remained significant when end-of-treatment abstinence was included as a covariate. Findings highlight the complex nature of self-efficacy's relation with drinking outcomes. Although the interaction between self-efficacy and behavioral processes was attenuated when end-of-treatment abstinence was controlled for, the quadratic effect of self-efficacy on outcomes remained significant. The pattern of these effects did not support the idea of "overconfidence" as a negative indicator.

  4. Cisplatin@US-tube Carbon Nanocapsules For Enhanced Chemotherapeutic Delivery

    PubMed Central

    Guven, Adem; Rusakova, Irene A.; Lewis, Michael T.; Wilson, Lon J.

    2012-01-01

    The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivity, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have also garnered attention in the area of drug delivery. In this study, we describe the preparation, characterization, and in vitro testing of a new ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectrometry (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 °C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic-F108 surfactant. Finally, the anticancer activity of pluronic-wrapped CDDP@US-tubes has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP after 24 hours. These studies have laid the foundation for developing US-tube-based delivery of chemotherapeutics, with drug release mainly limited to within cancer cells only. PMID:22078812

  5. Vilazodone in the treatment of major depressive disorder: efficacy across symptoms and severity of depression.

    PubMed

    Khan, Arif; Sambunaris, Angelo; Edwards, John; Ruth, Adam; Robinson, Donald S

    2014-03-01

    Vilazodone is a potent selective serotonin reuptake inhibitor and serotonin 1A receptor partial agonist approved for the treatment of major depressive disorder in adults. To assess the efficacy of vilazodone across a range of symptoms and severities of depression, data from two phase III, 8-week, randomized, double-blind, placebo-controlled trials were pooled for analysis. Overall improvement in depressive symptoms measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) and the 17-item Hamilton Depression Rating Scale was statistically significant (P<0.05) for vilazodone treatment compared with placebo as early as Week 1 and continued throughout double-blind treatment. Vilazodone treatment compared with placebo showed significant improvement on all 10 individual MADRS symptom items at end of treatment (P<0.01). Rates of response and remission were significantly greater in the vilazodone group relative to the placebo group, with numbers needed to treat ranging from eight to nine for response and 12-17 for remission. Between-group treatment differences in MADRS and the other outcome measures were similar among all depression subgroups, with no consistent pattern associated with depression severity. These findings support the efficacy of vilazodone across a broad range of depressive symptoms and severities for the treatment of major depressive disorder.

  6. Assessment of the Efficacy and Safety of a New Treatment for Head Lice

    PubMed Central

    Mac-Mary, Sophie; Messikh, Rafat; Jeudy, Adeline; Lihoreau, Thomas; Sainthillier, Jean-Marie; Gabard, Bernard; Schneider, Catherine; Auderset, Philippe; Humbert, Philippe

    2012-01-01

    Infestation with head lice is a widespread, persistent, and recurring issue leading to serious health problems if untreated. We are facing resistance phenomena to usual pediculicides and questions about their direct or cumulative toxicity. The aim of this trial was to assess the efficacy of a new product, free of chemical insecticides but with a physical effect. This product contains components whose antilice efficacy has already been demonstrated, as well as Andiroba oil which asphyxiates the lice and Quassia vinegar which dissolves the chitin of the nits (they are then inactivated). 30 patients with head lice infestation, aged 3–39 years, applied the treatment one to three times, 5 days apart. Cure was defined as the absence of live lice after 5, 10, or 14 days, and symptoms are usually associated with infestation. Easiness and safety of the treatment were assessed by the patients and/or their parents. Overall cure rates were 20% on D5 after one treatment, 37% on D10 after two treatments, and 90% on D14 after three treatments. Symptoms such as itch, scalp dryness, redness, and flakiness rapidly diminished. This treatment seems to be a beneficial addition or a valuable alternative to existing treatments, considering the total absence of chemical insecticides, the absence of drug-resistance induction in head lice, the absence of major toxicological risks compared with usual pediculicides, and the favourable patient use instructions. PMID:23209928

  7. Assessment of the efficacy and safety of a new treatment for head lice.

    PubMed

    Mac-Mary, Sophie; Messikh, Rafat; Jeudy, Adeline; Lihoreau, Thomas; Sainthillier, Jean-Marie; Gabard, Bernard; Schneider, Catherine; Auderset, Philippe; Humbert, Philippe

    2012-01-01

    Infestation with head lice is a widespread, persistent, and recurring issue leading to serious health problems if untreated. We are facing resistance phenomena to usual pediculicides and questions about their direct or cumulative toxicity. The aim of this trial was to assess the efficacy of a new product, free of chemical insecticides but with a physical effect. This product contains components whose antilice efficacy has already been demonstrated, as well as Andiroba oil which asphyxiates the lice and Quassia vinegar which dissolves the chitin of the nits (they are then inactivated). 30 patients with head lice infestation, aged 3-39 years, applied the treatment one to three times, 5 days apart. Cure was defined as the absence of live lice after 5, 10, or 14 days, and symptoms are usually associated with infestation. Easiness and safety of the treatment were assessed by the patients and/or their parents. Overall cure rates were 20% on D5 after one treatment, 37% on D10 after two treatments, and 90% on D14 after three treatments. Symptoms such as itch, scalp dryness, redness, and flakiness rapidly diminished. This treatment seems to be a beneficial addition or a valuable alternative to existing treatments, considering the total absence of chemical insecticides, the absence of drug-resistance induction in head lice, the absence of major toxicological risks compared with usual pediculicides, and the favourable patient use instructions.

  8. Efficacy of C1 esterase inhibitor concentrate in treatment of cutaneous attacks of hereditary angioedema

    PubMed Central

    Bork, Konrad; Craig, Timothy J.; Bernstein, Jonathan A.; Feuersenger, Henrike; Machnig, Thomas

    2015-01-01

    Background: Although treatment with C1 esterase inhibitor (C1-INH) concentrate is well established for hereditary angioedema (HAE) attacks in general, data that assess its efficacy for cutaneous attack treatment are sparse. Objective: To assess efficacy of plasma-derived, nanofiltered C1-INH concentrate for cutaneous attack treatment by comparing treated attacks from the uncontrolled I.M.P.A.C.T.2 study with historical data for untreated attacks. Methods: Cutaneous attack data from patients with HAE who were treated for cutaneous edema with 20 IU/kg body weight C1-INH concentrate in the uncontrolled I.M.P.A.C.T.2 study (38 patients) were compared with data from untreated patients from an historical data base (46 patients) and included subset analyses for facial edema (treated group, 21 patients; untreated group, 33 patients) and peripheral edema (30 patients in each group). Average attack duration (AAD) per patient was the efficacy end point used to compare treated and untreated patients. Differences were assessed with a Wilcoxon test (primary analysis) and a log-rank test; AAD per patient was analyzed descriptively and graphically with Kaplan-Meier curves. Results: The AAD per patient of all cutaneous attacks or facial and peripheral cutaneous attack subsets was significantly faster with C1-INH treatment than without treatment (Wilcoxon and log-rank tests, both p < 0.0001 for all comparisons). Mean AADs per patient for all, facial, and peripheral attacks were 2.04, 1.45, and 2.16 days, respectively, in the C1-INH–treated group, and were 3.74, 4.45, and 2.98 days, respectively, in the untreated group. Kaplan-Meier curves corroborated the observed group differences. Conclusion: Treatment of cutaneous HAE attacks (all attacks or facial and peripheral attack subsets) with 20 IU/kg C1-INH concentrate provided faster attack resolution compared with no treatment. PMID:25803207

  9. PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies

    PubMed Central

    2016-01-01

    Platelet-Rich Plasma (PRP) has been widely used in orthopaedic surgery and sport medicine to treat tendon injuries. However, the efficacy of PRP treatment for tendinopathy is controversial. This paper focuses on reviewing the basic science studies on PRP performed under well-controlled conditions. Both in vitro and in vivo studies describe PRP's anabolic and anti-inflammatory effects on tendons. While some clinical trials support these findings, others refute them. In this review, we discuss the effectiveness of PRP to treat tendon injuries with evidence presented in basic science studies and the potential reasons for the controversial results in clinical trials. Finally, we comment on the approaches that may be required to improve the efficacy of PRP treatment for tendinopathy.

  10. Random effects logistic models for analysing efficacy of a longitudinal randomized treatment with non-adherence.

    PubMed

    Small, Dylan S; Ten Have, Thomas R; Joffe, Marshall M; Cheng, Jing

    2006-06-30

    We present a random effects logistic approach for estimating the efficacy of treatment for compliers in a randomized trial with treatment non-adherence and longitudinal binary outcomes. We use our approach to analyse a primary care depression intervention trial. The use of a random effects model to estimate efficacy supplements intent-to-treat longitudinal analyses based on random effects logistic models that are commonly used in primary care depression research. Our estimation approach is an extension of Nagelkerke et al.'s instrumental variables approximation for cross-sectional binary outcomes. Our approach is easily implementable with standard random effects logistic regression software. We show through a simulation study that our approach provides reasonably accurate inferences for the setting of the depression trial under model assumptions. We also evaluate the sensitivity of our approach to model assumptions for the depression trial.

  11. PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies

    PubMed Central

    2016-01-01

    Platelet-Rich Plasma (PRP) has been widely used in orthopaedic surgery and sport medicine to treat tendon injuries. However, the efficacy of PRP treatment for tendinopathy is controversial. This paper focuses on reviewing the basic science studies on PRP performed under well-controlled conditions. Both in vitro and in vivo studies describe PRP's anabolic and anti-inflammatory effects on tendons. While some clinical trials support these findings, others refute them. In this review, we discuss the effectiveness of PRP to treat tendon injuries with evidence presented in basic science studies and the potential reasons for the controversial results in clinical trials. Finally, we comment on the approaches that may be required to improve the efficacy of PRP treatment for tendinopathy. PMID:27610386

  12. PRP Treatment Efficacy for Tendinopathy: A Review of Basic Science Studies.

    PubMed

    Zhou, Yiqin; Wang, James H-C

    2016-01-01

    Platelet-Rich Plasma (PRP) has been widely used in orthopaedic surgery and sport medicine to treat tendon injuries. However, the efficacy of PRP treatment for tendinopathy is controversial. This paper focuses on reviewing the basic science studies on PRP performed under well-controlled conditions. Both in vitro and in vivo studies describe PRP's anabolic and anti-inflammatory effects on tendons. While some clinical trials support these findings, others refute them. In this review, we discuss the effectiveness of PRP to treat tendon injuries with evidence presented in basic science studies and the potential reasons for the controversial results in clinical trials. Finally, we comment on the approaches that may be required to improve the efficacy of PRP treatment for tendinopathy. PMID:27610386

  13. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study.

    PubMed

    Boccard, Sandra G; Marand, Sandie V; Geraci, Sandra; Pycroft, Laurie; Berger, François R; Pelletier, Laurent A

    2015-10-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  14. Inhibition of DNA-repair genes Ercc1 and Mgmt enhances temozolomide efficacy in gliomas treatment: a pre-clinical study

    PubMed Central

    Boccard, Sandra G.; Marand, Sandie V.; Geraci, Sandra; Pycroft, Laurie; Berger, François R.; Pelletier, Laurent A.

    2015-01-01

    Gliomas are the most common primary brain tumors. To date, therapies do not allow curing patients, and glioblastomas (GBMs) are associated with remarkably poor prognosis. This situation is at least partly due to intrinsic or acquired resistance to treatment, especially to chemotherapy. In 2005, temozolomide (TMZ) has become the first chemotherapeutic drug validated for GBM. Nevertheless TMZ efficacy depends on Mgmt status. While the methylation of Mgmt promoter was considered so far as a prognostic marker, its targeting is becoming an effective therapeutic opportunity. Thus, arrival of both TMZ and Mgmt illustrated that considerable progress can still be realized by optimizing adjuvant chemotherapy. A part of this progress could be accomplished in the future by overcoming residual resistance. The aim of the present study was to investigate the involvement of a set of other DNA-repair genes in glioma resistance to temozolomide. We focused on DNA-repair genes located in the commonly deleted chromosomal region in oligodendroglioma (1p/19q) highly correlated with patient response to chemotherapy. We measured effects of inhibition of ten DNA-repair genes expression using siRNAs on astrocytoma cell response to cisplatin (CDDP) and TMZ. SiRNAs targeting ercc1, ercc2, mutyh, and pnkp significantly sensitized cells to chemotherapy, increasing cell death by up to 25%. In vivo we observed a decrease of subcutaneous glioma tumor growth after injection of siRNA in conjunction with absorption of TMZ. We demonstrated in this pre-clinical study that targeting of DNA-repair genes such as Ercc1 could be used as an adjuvant chemosensitization treatment, similarly to Mgmt inhibition. PMID:26336131

  15. Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells.

    PubMed

    Hussain, Arif; Brahmbhatt, Kruti; Priyani, Anita; Ahmed, Musthaq; Rizvi, Tahir A; Sharma, Chhavi

    2011-10-01

    Administration of natural or synthetic agents to inhibit, delay, block, or reverse the initiation and promotional events associated with carcinogenesis opens a new avenue for cancer prevention and treatment to reduce cancer morbidity and mortality. Eugenol, a potential chemopreventive agent, is a component of clove and several other spices such as basil, cinnamon, and bay leaves. A number of reports have shown that eugenol possesses antiseptic, analgesic, antibacterial, and anticancer properties. The present study was undertaken to evaluate the chemopreventive potential of eugenol alone and in combination with a chemotherapeutic agent such as gemcitabine. Eugenol showed dose-dependent selective cytotoxicity toward HeLa cells in comparison to normal cells, pointing to its safe cytotoxicity profile. A combination of eugenol and gemcitabine induced growth inhibition and apoptosis at lower concentrations, compared with the individual drugs. The analysis of the data using a combination index showed combination index values of <1 indicating strong synergistic interaction. The combination thus may enhance the efficacy of gemcitabine at lower doses and minimize the toxicity on normal cells. In addition, the expression analysis of genes involved in apoptosis and inflammation revealed significant downregulation of Bcl-2, COX-2, and IL-1β on treatment with eugenol. Thus, the results suggest that eugenol exerts its anticancer activities via apoptosis induction and anti-inflammatory properties and also provide the first evidence demonstrating synergism between eugenol and gemcitabine, which may enhance the therapeutic index of prevention and/or treatment of cervical cancer.

  16. [Clinical efficacy and achievement of a complete remission in depression: increasing interest in treatment with escitalopram].

    PubMed

    Favré, P

    2012-02-01

    Such a prevalent disease as Major Depressive Disorder (MDD), associated with prominent impairment in physical and social functioning, implies as well an increased morbidity and mortality. Long-term treatments are required due to the frequent occurrence of relapses. Patient compliance is a core factor in both acute and continuation treatment, closely related to tolerability issues. We have partially reviewed the literature published on PubMed since 2004 which assess the relative antidepressant efficacy of escitalopram and comparator antidepressants in adult patients who met DSM-IV criteria for major depressive disorder (MDD). Clinically important differences exist between commonly prescribed antidepressants. These analyses are in favor of a superior efficacy and tolerability of long-term escitalopram treatment (10 to 20mg/day) compared with active controls, including selective serotonin re-uptake inhibitors (SSRIs) (paroxetine, citalopram, bupropion, fluoxetine, fluvoxamine, sertraline), serotonin/noradrenaline reuptake inhibitors (SNRIs) (venlafaxine, milnacipran and duloxetine) and noradrenergic and specific serotonergic antidepressants (NaSSAs) (mirtazapine). Cipriani et al. (2009) have performed a network meta-analysis of 12 new generation antidepressants. They have shown that clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favor of escitalopram and sertraline in acute treatment, defined as 8-week treatment. Kasper et al. (2009) conducted a post-hoc pooled analysis of data from two 6-month randomized controlled trials that revealed superior efficacy and tolerability of escitalopram when compared with paroxetine. The pooled analysis of four randomized, double-blind, active comparator, 6-month trials in MDD, by Wade et al. (2009), showed that short-term outcomes may predict long-term treatment compliance and outcomes. A higher probability of achieving remission was associated with responding

  17. [EFFICACY OF SURGICAL TREATMENT OF VARICOSE DISEASE, DEPENDING ON ADSORPTION-RHEOLOGIC PROPERTIES OF BLOOD].

    PubMed

    Grihn, V K; Kondratenko, P G; Melekhovets, Yu V; Sinyachenko, Yu O; Sinyachenko, O V

    2015-05-01

    Physico-chemical adsorption-rheological properties of venous blood in patients, suffering varicose disease of the lower extremities, and their impact on efficacy of various methods of surgical treatment were studied. Conduction of endovasal laser coagulation in combination with crossectomy have promoted enhancement of operative treatment efficacy in patients in initial terms of observation (in 1 week), in 1 month a complete occlusion of the vein was noted more rarely. Efficacy of a small--power laser ablation with irradiation power of 10 W and less in 4 weeks postoperatively is higher, than of surgical treatment with a laser irradiation power 15 W. In a varicose disease of the lower extremities there were observed the raising of the blood volume toughness, superficial relaxation and superficial stress on background of reduction of the toughness--elasticity module, superficial toughness and superficial elasticity. Crossectomy conduction did not influence the integral dynamics of adsorption--rheological properties of venous blood, but in 1 month after endovasal laser coagulation a normalization of physicchemical parameters of blood was noted. Application of laser irradiation of the 10 W power and less promotes inhibition of the relaxation properties of venous blood; a prognostic meaning owes initial value of the blood volume toughness.

  18. Efficacy and safety of tanezumab versus naproxen in the treatment of chronic low back pain.

    PubMed

    Kivitz, Alan J; Gimbel, Joseph S; Bramson, Candace; Nemeth, Mary Anne; Keller, David S; Brown, Mark T; West, Christine R; Verburg, Kenneth M

    2013-07-01

    Tanezumab is a humanized monoclonal antibody that specifically inhibits nerve growth factor as a treatment for chronic pain. This phase IIB study investigated the efficacy and safety of tanezumab for chronic low back pain vs placebo and naproxen. Patients (N=1347) received intravenous tanezumab (5, 10, or 20mg every 8weeks), naproxen (500mg twice daily), or placebo. The primary efficacy end point was mean change in daily average low back pain intensity (LBPI) from baseline to week 16. Secondary end points included mean change from baseline to week 16 in the Roland Morris Disability Questionnaire and Patient's Global Assessment (PGA) of low back pain. Tanezumab 10 and 20mg had similar efficacy profiles and significantly improved LBPI, Roland Morris Disability Questionnaire, and PGA scores vs both placebo and naproxen (P⩽.05). Tanezumab 5mg provided improvement of PGA scores vs placebo (P⩽.05), and naproxen resulted in significant improvement of LBPI vs placebo (P⩽.05). Adverse event incidence was comparable across tanezumab doses but higher than with placebo or naproxen. Arthralgia, pain in extremity, headache, and paresthesia were the most commonly reported adverse events by tanezumab-treated patients. The most frequently reported adverse events resulting in discontinuation of tanezumab treatment were arthralgia and paresthesia; the highest frequency was observed with tanezumab 20mg (both 1.4%). Serious adverse event incidence was similar across treatments. In conclusion, tanezumab provided significantly greater improvement in pain, function, and global scores vs placebo and naproxen in patients with chronic low back pain.

  19. Role of chemotherapeutic antagonism in opportunistic infections.

    PubMed

    Castelli, M; Baggio, G; Ruberto, A I; Malagoli, M; Casolari, C; Rossi, T; Galatulas, I

    1997-01-01

    The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses. Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection. We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this. By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites. The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic. In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.

  20. Carbon nanofibers and carbon nanotubes sensitize prostate and bladder cancer cells to platinum-based chemotherapeutics.

    PubMed

    Ringel, Jessica; Erdmann, Kati; Hampel, Silke; Kraemer, Kai; Maier, Diana; Arlt, Marcus; Kunze, Doreen; Wirth, Manfred P; Fuessel, Susanne

    2014-03-01

    Recent data suggest that carbon nanomaterials can act as antitumor agents themselves by increasing the efficiency of cytotoxic agents when applied in combination. Here, carbon nanofibers (CNFs) and multi-walled carbon nanotubes (CNTs) were investigated regarding their impact on cellular function, cellular uptake and ability to sensitize cancer cells of urological origin to the conventional chemotherapeutics cisplatin and carboplatin. CNFs and CNTs (1-200 microg/ml) showed a low to moderate impairment of cellular function with CNFs being more deleterious than CNTs. Inhibition of cellular viability by the nanomaterials was about 20% at most. In combinatory treatments, CNFs and CNTs markedly enhanced the effects of cisplatin and carboplatin on cellular viability by 1.2- to 2.8-fold in prostate, bladder and cisplatin-resistant prostate cancer cells in comparison to the individual effects of the chemotherapeutics. Particularly the cell viability-diminishing effect of CNFs alone and in combination with the chemotherapeutics was more pronounced with dispersions prepared with human serum albumin than with phospholipid-polyethylene glycol. Albumin might mediate the cellular uptake of carbon nanomaterials which was underlined by the co-localization of albumin and carbon nanomaterials along the cellular surface as evidenced by fluorescence microscopy. Transmission electron microscopy revealed that both carbon nanomaterials were internalized by cancer cells, thereby possibly leading to an enhanced accumulation of the chemotherapeutic drugs. In fact, CNFs enhanced the cellular accumulation of carboplatin by 28% as compared to the single treatment with carboplatin. In conclusion, carbon nanomaterial-based applications could present a new strategy to overcome chemoresistance by sensitizing cancer cells to conventional chemotherapeutics.

  1. Clinical efficacy of milbemycin oxime in the treatment of nasal mite infection in dogs.

    PubMed

    Gunnarsson, L K; Möller, L C; Einarsson, A M; Zakrisson, G; Hagman, B G; Christensson, D A; Uggla, A H; Hedhammar, A A

    1999-01-01

    A multicentric clinical trial was done to evaluate the clinical efficacy of milbemycin oxime in the treatment of nasal mite (Pneumonyssoides caninum) infection in dogs. Milbemycin oxime was given to 70 dogs of different breeds, genders, and ages, with clinical signs associated with nasal mite infection. Twenty-five dogs had a verified infection, and 45 dogs had signs suggestive of nasal mite infection. Milbemycin oxime was given at the dosage of 0.5 to 1.0 mg/kg body weight orally once a week for three consecutive weeks. One month after initiation of treatment, 68 of the dogs had no more clinical signs associated with nasal mite infection.

  2. A meta-analysis of the efficacy of fibromyalgia treatment according to level of care

    PubMed Central

    Garcia-Campayo, Javier; Magdalena, Jesus; Magallón, Rosa; Fernández-García, Esther; Salas, Montserrat; Andrés, Eva

    2008-01-01

    Introduction The aim of this paper was to compare the efficacy of the treatments for fibromyalgia currently available in both primary care and specialised settings. Methods Published reports of randomised controlled trials (RCTs) researching pharmacological and non-pharmacological treatments in patients with fibromyalgia were found in the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and PsychInfo databases. The most recent electronic search was undertaken in June 2006. Results We identified a total of 594 articles. Based on titles and abstracts, 102 full articles were retrieved, 33 of which met the inclusion criteria. These RCTs assessed 120 treatment interventions in 7789 patients diagnosed with primary fibromyalgia. Of them, 4505 (57.8%) were included in the primary care group of our study and 3284 (42.2%) in the specialised intervention group. The sample was mostly made up of middle-aged women, who have had fibromyalgia for a mean period of 6 to 10 years. The mean effect size of the efficacy of the 120 treatment interventions in patients with fibromyalgia compared with controls was 0.49 (95% confidence interval [CI] = 0.39 to 0.58; p < 0.001). In the primary care group it was 0.46 (95% CI = 0.33 to 0.58) while in specialised care it was 0.53 (95% CI = 0.38 to 0.69), with no statistical significance in the differences. We analysed the efficacy of treatments by comparing primary and specialised care in the different fibromyalgia groups and there were no significant differences. The variables of the studies that affected the improvements in the efficacy of fibromyalgia treatment were low quality of the studies and a shorter duration of treatment. However, both factors were biased by the heterogeneity of the studies. Other variables that also improved outcome and were not biased by the heterogeneity of the studies, were younger age of the patients and shorter duration of the disorder. On the contrary, gender and type of treatment

  3. Safety of Chemotherapeutic Infusion or Chemoembolization for Hepatocellular Carcinoma Supplied Exclusively by the Cystic Artery

    SciTech Connect

    Kang, Beomsik Kim, Hyo-Cheol Chung, Jin Wook Hur, Saebeom Joo, Seung-Moon Jae, Hwan Jun Park, Jae Hyung

    2013-10-15

    Purpose: This study was designed to evaluate the safety of chemotherapeutic infusion or chemoembolization by way of the cystic artery in patients with hepatocellular carcinoma (HCC) supplied exclusively by the cystic artery. Methods: Between Jan 2002 and Dec 2011, we performed chemotherapeutic infusion or chemoembolization using iodized oil for the treatment of 27 patients with HCC supplied exclusively by the cystic artery. Computed tomography (CT) scans, digital subtraction angiograms, and medical records were retrospectively reviewed by consensus. Results: The cystic artery originated from the main right hepatic artery in 24 (89 %) patients, from the right anterior hepatic artery in 2 (7 %) patients, and from the left hepatic artery in 1 (4 %) patient. Selective catheterization of the cystic artery was achieved in all patients. Superselection of tumor-feeding vessels from the cystic artery was achieved in 7 patients (26 %). Chemotherapeutic infusion was performed in 18 patients (67 %), and chemoembolization was performed in 9 patients (33 %). There were no major complications and only 2 minor complications, including vasovagal syncope and nausea with vomiting. Individual tumor response supplied exclusively by the cystic artery at the follow-up enhanced CT scan were complete response (n = 16), partial response (n = 3), and stable disease (n = 8). Conclusion: HCC supplied exclusively by the cystic artery can be safely treated without severe complications by chemotherapeutic infusion or chemoembolization using iodized oil through the cystic artery.

  4. The efficacy of topical ivermectin versus malation 0.5% lotion for the treatment of scabies.

    PubMed

    Goldust, Mohamad; Rezaee, Elham

    2013-05-01

    Objective: There are different medications for the treatment of scabies but the treatment of choice is still controversial. This study aimed at comparing the efficacy of topical ivermectin versus malation 0.5% lotion for the treatment of scabies. Methods: In total, 340 patients with scabies were enrolled, and randomized into two groups: the first group received 1% ivermectin applied topically to the affected skin and the second group received topical malation 0.5% lotion and were told to apply this twice with 1 week interval. Treatment was evaluated at intervals of 2 and 4 weeks, and if there was treatment failure at the 2-week follow-up, treatment was repeated. Results: Two application of topical ivermectin provided a cure rate of 67.6% at the 2-week follow-up, which increased to 85.2% at the 4-week follow-up after repeating the treatment. Treatment with two applications of malation 0.5% lotion was effective in 44.1% of patients at the 2-week follow-up, which increased to 67.6% at the 4-week follow-up after this treatment was repeated. Conclusion:Two application of ivermectin was as effective as single applications of malation 0.5% lotion at the 2-week follow-up. After repeating the treatment, ivermectin was superior to malation 0.5% lotion at the 4-week follow up.

  5. Apparent subadditivity of the efficacy of initial combination treatments for type 2 diabetes is largely explained by the impact of baseline HbA1c on efficacy

    PubMed Central

    Capuano, G.; Qiu, R.

    2016-01-01

    Aim To explain the subadditive efficacy typically observed with initial combination treatments for type 2 diabetes. Methods Individual subject data from 1186 patients with type 2 diabetes [mean glycated haemoglobin (HbA1c) = 8.8%] treated with metformin, canagliflozin or canagliflozin + metformin were used. The baseline HbA1c versus ΔHbA1c relationships for monotherapy arms were determined using analysis of covariance and then used to predict efficacy in the combination arms by modelling how applying one treatment lowers the ‘effective baseline HbA1c’ for a second treatment. The model was further tested using data from several published combination studies. Results The mean ΔHbA1c levels were −1.25, −1.33, −1.37, −1.77 and −1.81% with metformin, canagliflozin 100 mg, canagliflozin 300 mg, canagliflozin 100 mg/metformin and canagliflozin 300 mg/metformin, respectively. Using the monotherapy results, the predicted efficacy for the canagliflozin/metformin arms was within 10% of the observed values using the new model, whereas assuming simple additivity overpredicted efficacy in the combination arms by nearly 50%. For 10 other published initial combination studies, predictions from the new model [mean (standard error) predicted ΔHbA1c = 1.67% (0.14)] were much more consistent with observed values [ΔHbA1c = 1.72% (0.12)] than predictions based on assuming additivity [predicted ΔHbA1c = 2.19% (0.21)]. Conclusions The less‐than‐additive efficacy commonly seen with initial combination treatments for type 2 diabetes can be largely explained by the impact of baseline HbA1c on the efficacy of individual treatments. Novel formulas have been developed for predicting the efficacy of combination treatments based on the efficacy of individual treatments and the baseline HbA1c of the target patients. PMID:26661906

  6. Duloxetine in the treatment of major depressive disorder: comparisons of safety and efficacy.

    PubMed Central

    Bailey, Rahn K.; Mallinckrodt, Craig H.; Wohlreich, Madelaine M.; Watkin, John G.; Plewes, John M.

    2006-01-01

    BACKGROUND: Pooled data from double-blind, placebo-controlled studies were utilized to compare the safety and efficacy of duloxetine in the treatment of major depressive disorder (MDD) in African-American and Caucasian patients. METHODS: Efficacy and safety data were pooled from seven double-blind, placebo-controlled clinical trials of duloxetine. Patients (aged > or =18 years) meeting DSM-IV criteria for MDD received duloxetine (40-120 mg/day; African Americans, N=69; Caucasians, N=748) or placebo (African Americans, N=59; Caucasians, N=594) for up to nine weeks. Efficacy measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, the Clinical Global Impression of Severity (CGI-S) and Patient Global Impression of Improvement (PGI-I) scales, and Visual Analog Scales (VAS) for pain. Safety was assessed using discontinuation rates, spontaneously reported treatment-emergent adverse events, vital signs and laboratory analyses, RESULTS: Based upon mean changes in HAMD17, CGI-S and PGI-I scales, the magnitude of duloxetine's treatment effects did not differ significantly between African-American and Caucasian patients. Discontinuation rates due to adverse events among duloxetine-treated patients were 13.0% for African Americans and 17.0% for Caucasians. No adverse event led to discontinuation in more than one African-American patient. The most common treatment-emergent adverse events in both ethnic groups included nausea, headache, constipation, dizziness and insomnia. The rate of occurrence of these events did not differ significantly between African-American and Caucasian patients. Mean changes from baseline for pulse, blood pressure, weight and laboratory analytes were small and showed no significant differences between African-American and Caucasian patients. CONCLUSION: In this analysis of data from seven clinical trials, no convincing evidence was found to suggest that the overall safety and tolerability profile or the efficacy profile

  7. Efficacy of Chloroquine for the Treatment of Vivax malaria in Northwest Ethiopia

    PubMed Central

    Beyene, Habtamu Bedimo; Beyene, Melkamu Bedimo; Ebstie, Yehenew Asmamaw; Desalegn, Zelalem

    2016-01-01

    Background Resistance to anti-malarials is a major challenge for effective malaria control in sub-Saharan Africa. This triggered a need for routine monitoring of the efficacy of the antimalarial drugs every two years in all malaria endemic countries. Chloroquine remained the drug of choice for the treatment of vivax malaria in Ethiopia. Though, a strong scientific evidence of chloroquine resistance to P.vivax that could have brought change of treatment regimen is yet to be established in Ethiopia, continuous and regular monitoring of drug’s efficacy is critical for establishing rational anti-malarial drug policies. This study therefore, assessed the therapeutic efficacy of Chloroquine (CQ) for the treatment of Plasmodium vivax infections in Northwestern Ethiopia. Methods An observational, 28- day therapeutic clinical efficacy study was conducted from August to December, 2014, in Northwest Ethiopia. Patients confirmed to have monoinfection of vivax malaria, aged above 6 months were included. All subjects were treated with standard chloroquine dose of 25 mg/kg for three (3) days. Parasitological and clinical outcomes of treated patients were then evaluated on days 1, 2, 3, 7, 14, 21, and 28 during the entire 28-day follow-up period. A portable spectrophotometer (HemoCue Hb 301 System, Sweden) was used to estimate hemoglobin concentration. Results A total of 69 subjects had completed follow up. Some 57/69 (82.6%) had fever at enrolment and the rest 12 patients 48 hours before enrollment. Out of total, 65/69 (94.2%) and 66/69 (95.6%) of the study subjects were free of fever by day 1 and day 2 respectively but fever was cleared in all subjects by day 3. At base line the mean asexual parasitemia was 3540 parasites/μL of blood. Parasite carriage on day 3 was 3%. The overall cure rate (an adequate and clinical parasitological response) was very high (97%) [(95% CI = 93.1–99.4)]. The time to parasite, fever and gametocyte clearance as expressed in mean (SD) was 35 (3

  8. Efficacy of Virtual Reality Exposure Therapy in the Treatment of PTSD: A Systematic Review

    PubMed Central

    Gonçalves, Raquel; Pedrozo, Ana Lúcia; Coutinho, Evandro Silva Freire; Figueira, Ivan; Ventura, Paula

    2012-01-01

    The use of Information and Communication Technologies, such as virtual reality, has been employed in the treatment of anxiety disorders with the goal of augmenting exposure treatment, which is already considered to be the first-line treatment for Post-traumatic Stress Disorder (PTSD). To evaluate the efficacy of virtual reality exposure therapy (VRET) in the treatment of PTSD, we performed a systematic review of published articles using the following electronic databases: Web of Science, PubMed, PsycINFO, and PILOTS. Eligibility criteria included the use of patients diagnosed with PTSD according to DSM-IV, the use of cognitive behavioral therapy (CBT) and the use of virtual reality for performing exposure. 10 articles were selected, seven of which showed that VRET produced statistically significant results in comparison to the waiting list. However, no difference was found between VRET and exposure treatment. Of these 10, four were randomized, two were controlled but not randomized and four were non-controlled. The majority of the articles used head-mounted display virtual reality (VR) equipment and VR systems specific for the population that was being treated. Dropout rates do not seem to be lower than in traditional exposure treatment. However, there are a few limitations. Because this is a new field of research, there are few studies in the literature. There is also a need to standardize the number of sessions used. The randomized studies were analyzed to assess the quality of the methodology, and important deficiencies were noted, such as the non-use of intent-to- treat-analysis and the absence of description of possible concomitant treatments and comorbidities. Preliminary data suggest that VRET is as efficacious as traditional exposure treatment and can be especially useful in the treatment of patients who are resistant to traditional exposure. PMID:23300515

  9. Efficacy Profiles of Daptomycin for Treatment of Invasive and Noninvasive Pulmonary Infections with Streptococcus pneumoniae▿

    PubMed Central

    Henken, Stefanie; Bohling, Jennifer; Martens-Lobenhoffer, Jens; Paton, James C.; Ogunniyi, A. David; Briles, David E.; Salisbury, Vyvyan C.; Wedekind, Dirk; Bode-Böger, Stefanie M.; Welsh, Thomas; Bange, Franz C.; Welte, Tobias; Maus, Ulrich A.

    2010-01-01

    Daptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to ∼70% or ∼60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease. PMID:19917756

  10. Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis

    PubMed Central

    Frieri, Marianne; Heuser, William; Bliss, Joshua

    2015-01-01

    Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) that can lead to significant illness or even death without proper intervention and treatment. With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targeting B cell signaling and maturation, belimumab is able to mitigate the underlying pathological complications surrounding SLE. Phase 3 clinical trials with belimumab have depicted clinically efficacious applications, suggesting belimumab as a revolutionary breakthrough in the treatment armamentarium for practicing clinicians. This article explains the precise mechanism of action of belimumab on the soluble protein BlyS that plays a major role in the pathogenesis of lupus nephritis. In addition, the extensive pharmacokinetics and clinical implications are exemplified in this review with belimumab's comparison with standard therapeutic guidelines for the treatment of lupus nephritis. PMID:25969652

  11. Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.

    PubMed

    Ramon, Silvia; Gleitz, Markus; Hernandez, Leonor; Romero, Luis David

    2015-12-01

    Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM).

  12. Endovascular Treatment of Malignant Superior Vena Cava Syndrome: Results and Predictive Factors of Clinical Efficacy

    SciTech Connect

    Fagedet, Dorothee; Thony, Frederic; Timsit, Jean-Francois; Rodiere, Mathieu; Monnin-Bares, Valerie; Ferretti, Gilbert R.; Vesin, Aurelien; Moro-Sibilot, Denis

    2013-02-15

    To demonstrate the effectiveness of endovascular treatment (EVT) with self-expandable bare stents for malignant superior vena cava syndrome (SVCS) and to analyze predictive factors of EVT efficacy. Retrospective review of the 164 patients with malignant SVCS treated with EVT in our hospital from August 1992 to December 2007 and followed until February 2009. Endovascular treatment includes angioplasty before and after stent placement. We used self-expandable bare stents. We studied results of this treatment and looked for predictive factors of clinical efficacy, recurrence, and complications by statistical analysis. Endovascular treatment was clinically successful in 95% of cases, with an acceptable rate of early mortality (2.4%). Thrombosis of the superior vena cava was the only independent factor for EVT failure. The use of stents over 16 mm in diameter was a predictive factor for complications (P = 0.008). Twenty-one complications (12.8%) occurred during the follow-up period. Relapse occurred in 36 patients (21.9%), with effective restenting in 75% of cases. Recurrence of SVCS was significantly increased in cases of occlusion (P = 0.01), initial associated thrombosis (P = 0.006), or use of steel stents (P = 0.004). Long-term anticoagulant therapy did not influence the risk of recurrence or complications. In malignancy, EVT with self-expandable bare stents is an effective SVCS therapy. These results prompt us to propose treatment with stents earlier in the clinical course of patients with SVCS and to avoid dilatation greater than 16 mm.

  13. Update on the efficacy of extracorporeal shockwave treatment for myofascial pain syndrome and fibromyalgia.

    PubMed

    Ramon, Silvia; Gleitz, Markus; Hernandez, Leonor; Romero, Luis David

    2015-12-01

    Chronic muscle pain syndrome is one of the main causes of musculoskeletal pathologies requiring treatment. Many terms have been used in the past to describe painful muscular syndromes in the absence of evident local nociception such as myogelosis, muscle hardening, myalgia, muscular rheumatism, fibrositis or myofascial trigger point with or without referred pain. If it persists over six months or more, it often becomes therapy resistant and frequently results in chronic generalized pain, characterized by a high degree of subjective suffering. Myofascial pain syndrome (MPS) is defined as a series of sensory, motor, and autonomic symptoms caused by a stiffness of the muscle, caused by hyperirritable nodules in musculoskeletal fibers, known as myofascial trigger points (MTP), and fascial constrictions. Fibromyalgia (FM) is a chronic condition that involves both central and peripheral sensitization and for which no curative treatment is available at the present time. Fibromyalgia shares some of the features of MPS, such as hyperirritability. Many treatments options have been described for muscle pain syndrome, with differing evidence of efficacy. Extracorporeal Shockwave Treatment (ESWT) offers a new and promising treatment for muscular disorders. We will review the existing bibliography on the evidence of the efficacy of ESWT for MPS, paying particular attention to MTP (Myofascial Trigger Point) and Fibromyalgia (FM). PMID:26363497

  14. Fungal aero-decontamination efficacy of mobile air-treatment systems.

    PubMed

    Fréalle, Emilie; Lestrez, Christophe; Skierlak, Tiphaine; Melboucy, Djallil; Guery, Benoît; Durand-Joly, Isabelle; Delhaes, Laurence; Loukili, Noureddine

    2011-11-01

    Immunosuppressed patients are at high risk of acquiring airborne fungal infections, mainly caused by Aspergillus species. Although HEPA filters are recommended to prevent environmental exposure, mobile air-treatment units can be an alternative. However, many different models of mobile units are available but there are few data on their fungal aero-decontamination efficacy and usefulness in the prevention of Aspergillus infections. Thus, we developed a challenge test, based on the aerosolization of 10(6) Aspergillus niger conidia, in order to compare the particle and fungal decontamination efficacy of the following four mobile air-treatment systems; Plasmair T2006, Mobil'Air 1200 (MA1200), Mobil'Air 600 (MA600) combined with Compact AirPur Mobile C250 (C250), and the prototype unit Compact AirPur Mobile 1800 (C1800). The use of all these air-treatment systems was able to significantly decrease the concentration of particles or fungal viable conidia. ISO7 was the maximum particle class reached within 20 min with the Plasmair T2006 and MA1200, 1 h by the combined MA600/C250, and 1 h and 30 min with the C1800. After 2 h, fungal counts were significantly lower with Plasmair T2006, MA1200 and the combined MA600/C250 (2.2 ± 1.9 to 5.0 ± 3.7 CFU/m(3)) than achieved with the C1800 (23.8 ± 12.8 CFU/m(3); P ≤ 6.0E-3). All the air-treatment systems were able to decrease aerial particle and fungal counts, but their efficacy was variable, depending on the units' air-treatment modalities and rates of air volume that was processed. This comparative study could be helpful in making an informed choice of mobile units, and in improving the prevention of air-transmitted fungal infections in non-protected areas.

  15. Efficacy of Diverse Antiparasitic Treatments for Cysticercosis in the Pig Model

    PubMed Central

    Gonzalez, Armando E.; Bustos, Javier A.; Jimenez, Juan A.; Rodriguez, Mary L.; Ramirez, Mercy G.; Gilman, Robert H.; Garcia, Hector H.

    2012-01-01

    Taenia solium cysticercosis infects pigs and humans. Because antiparasitic treatment for human cysticercosis has sub-optimal efficacy, alternative regimes are needed. Seven antiparasitic regimens were tested in 42 naturally infected pigs with cysticercosis, and compared with prednisone alone (n = 6) or no treatment (n = 6). The numbers of viable cysts in muscles and in the brain were examined after necropsy and were significantly decreased in pigs receiving combined albendazole plus praziquantel, albendazole alone, or oxfendazole. Pigs receiving praziquantel alone and nitazoxanide had numerous surviving cysts. Control (untreated) pigs and prednisone-treated pigs had many more viable cysts, suggesting no effect. Combined albendazole plus praziquantel, and oxfendazole, showed a strong cysticidal effect and provide suitable alternative treatments to be further explored for their use for treatment of human neurocysticercosis. PMID:22855760

  16. [Assessment of efficacy and tolerance of tanakan during treatment of sensorineural bradyacuasia and tympanophonia].

    PubMed

    Kunel'skaia, N L; Levina, Iu V; Krasiuk, A A; Doronina, O M

    2009-01-01

    The objective of the study was to evaluate efficacy and tolerance of tanakan during treatment of neurosensory hearing loss and subjective tinnitis supposedly of vascular etiology. The secondary purpose was to analyse late results of 3 month courses of therapy and changes in the clinical course of the disease during treatment and within 6 months after its termination. Tanakan was first given at a dose of 40 mg thrice daily for 90 days. Results of the treatment were estimated on days 90, 180, and 240. The second course (40 mg thrice daily for 90 days) was initiated 180 days after the end of the first one. The final outcome was evaluated on day 360. It was shown that monotherapy with tanakan effectively improved the hearing function and had the most pronounced beneficial effect on subjective tinnitus. Results of the treatment remained stable throughout the entire observation period (12 months). PMID:19491797

  17. Efficacy of a brief treatment for nightmares and sleep disturbances for veterans.

    PubMed

    Balliett, Noelle E; Davis, Joanne L; Miller, Katherine E

    2015-11-01

    Nightmares and sleep disturbances are common complaints among military Veterans (Plumb & Zelman, 2009) and may be difficult to eradicate (Forbes, Phelps, & McHugh, 2001). A treatment protocol (Exposure, Relaxation, and Rescription Therapy [ERRT]) targeting nightmares and sleep disturbances, which has been used effectively in civilian populations, was adapted for the military (ERRT-M). A pilot study evaluated the efficacy of ERRT-M in improving sleep quality and quantity and reducing nightmares, symptoms of posttraumatic stress disorder, and depression in a trauma-exposed, Veteran sample (N = 19). At 1 week after treatment, analyses revealed improvements in nightmare frequency and severity, depression, sleep quality, and insomnia severity. Treatment gains were maintained at a 2-month follow-up. Fifty percent of the sample was considered treatment responders (i.e., no nightmares in the previous week). Results of this pilot study suggest that directly targeting sleep and nightmares is successful in alleviating sleep disturbances and related psychopathology in some Veterans.

  18. Oncolytic reovirus synergizes with chemotherapeutic agents to promote cell death in canine mammary gland tumor

    PubMed Central

    Igase, Masaya; Hwang, Chung Chew; Kambayashi, Satoshi; Kubo, Masato; Coffey, Matt; Miyama, Takako Shimokawa; Baba, Kenji; Okuda, Masaru; Noguchi, Shunsuke; Mizuno, Takuya

    2016-01-01

    The oncolytic effects of reovirus in various cancers have been proven in many clinical trials in human medicine. Oncolytic virotherapy using reovirus for canine cancers is being developed in our laboratory. The objective of this study was to examine the synergistic anti-cancer effects of a combination of reovirus and low doses of various chemotherapeutic agents on mammary gland tumors (MGTs) in dogs. The first part of this study demonstrated the efficacy of reovirus in canine MGTs in vitro and in vivo. Reovirus alone exerted significant cell death by means of caspase-dependent apoptosis in canine MGT cell lines. A single injection of reovirus impeded growth of canine MGT tumors in xenografted mice, but was insufficient to induce complete tumor regression. The second part of this study highlighted the anti-tumor effects of reovirus in combination with low doses of paclitaxel, carboplatin, gemcitabine, or toceranib. Enhanced synergistic activity was observed in the MGT cell line treated concomitantly with reovirus and in all the chemotherapeutic agents except toceranib. In addition, combining reovirus with paclitaxel or gemcitabine at half dosage of half maximal inhibitory concentration (IC50) enhanced cytotoxicity by activating caspase 3. Our data suggest that the combination of reovirus and low dose chemotherapeutic agents provides an attractive option in canine cancer therapy. PMID:26733729

  19. Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer.

    PubMed

    Perney, Pascal; Duny, Yohan; Nalpas, Bertrand; Lallemant, Benjamin; Rigole, Hélène; Cartier, César; Garrel, Renaud; Azria, The Addict-Orl Study Group David; Blanc, François; Duhamel, Olivier; Neka, Meissa; Ichou, Marc; Le Bars, Yves; Pelletier, Stéphanie; Quantin, Xavier; Stoebner, Anne

    2013-08-01

    Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

  20. Coping strategies, hope, and treatment efficacy in pharmacoresistant inpatients with neurotic spectrum disorders

    PubMed Central

    Ociskova, Marie; Prasko, Jan; Kamaradova, Dana; Grambal, Ales; Kasalova, Petra; Sigmundova, Zuzana; Latalova, Klara; Vrbova, Kristyna

    2015-01-01

    Background Approximately 30%–60% of patients with neurotic spectrum disorders remain symptomatic despite treatment. Identifying the predictors of good response to psychiatric and psychotherapeutic treatment may be useful for increasing treatment efficacy in neurotic patients. The objective of this study was to investigate the influence of hope, coping strategies, and dissociation on the treatment response of this group of patients. Methods Pharmacoresistant patients, who underwent a 6-week psychotherapeutic program, were enrolled in the study. All patients completed the Clinical Global Impression (CGI) – both objective and subjective forms, Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI)-II at baseline and after 6 weeks. The COPE Inventory, the Adult Dispositional Hope Scale (ADHS), and the Dissociative Experiences Scale (DES) were completed at the start of the treatment. Results Seventy-six patients completed the study. The mean scores for all scales measuring the severity of the disorders (BAI, BDI-II, subjective and objective CGI) significantly decreased during the treatment. Several subscores of the COPE Inventory, the overall score of ADHS, and the overall score of DES significantly correlated with the treatment outcome. Multiple regression was used to find out which factors were the most significant predictors of the therapeutic outcomes. The most important predictors of the treatment response were the overall levels of hope and dissociation. Conclusion According to our results, a group of patients with a primary neurotic disorder, who prefer the use of maladaptive coping strategies, feel hopelessness, and have tendencies to dissociate, showed poor response to treatment. PMID:26028972

  1. Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents.

    PubMed

    Modica-Napolitano, Josephine S; Weissig, Volkmar

    2015-01-01

    Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy.

  2. Comparison between the efficacy of ginger and sumatriptan in the ablative treatment of the common migraine.

    PubMed

    Maghbooli, Mehdi; Golipour, Farhad; Moghimi Esfandabadi, Alireza; Yousefi, Mehran

    2014-03-01

    Frequency and torment caused by migraines direct patients toward a variety of remedies. Few studies to date have proposed ginger derivates for migraine relief. This study aims to evaluate the efficacy of ginger in the ablation of common migraine attack in comparison to sumatriptan therapy. In this double-blinded randomized clinical trial, 100 patients who had acute migraine without aura were randomly allocated to receive either ginger powder or sumatriptan. Time of headache onset, its severity, time interval from headache beginning to taking drug and patient self-estimation about response for five subsequent migraine attacks were recorded by patients. Patients(,) satisfaction from treatment efficacy and their willingness to continue it was also evaluated after 1 month following intervention. Two hours after using either drug, mean headaches severity decreased significantly. Efficacy of ginger powder and sumatriptan was similar. Clinical adverse effects of ginger powder were less than sumatriptan. Patients' satisfaction and willingness to continue did not differ. The effectiveness of ginger powder in the treatment of common migraine attacks is statistically comparable to sumatriptan. Ginger also poses a better side effect profile than sumatriptan.

  3. Efficacy of salicylic acid in the treatment of digital dermatitis in dairy cattle.

    PubMed

    Schultz, N; Capion, N

    2013-11-01

    Digital dermatitis (DD) is one of the most important causes of lameness in dairy cattle worldwide. The objective of this study was to evaluate the efficacy of salicylic acid in the treatment of the disease. A total of 201 DD lesions from 173 cows from four commercial dairy herds were evaluated at day 0 during routine hoof trimming and were allocated into two groups, namely, a control group given chlortetracycline spray, and a treatment group given 10 g of salicylic acid powder applied topically within a bandage. Pain, lesion size and clinical appearance (scored M0 to M4) were evaluated on days 3, 14 and 34 post-treatment. A change to M0 was defined as healing, while changes of M2 or M4 to M1 or M3 were classified as clinical improvements. Healing rates did not differ significantly between treatment groups at days 3 and 14. By day 34 the healing rate was fivefold better (P=0.01) for the treatment vs. the control group, with healing rates of 13.6% and 3.1%, respectively. By day 3, the rate of improvement was 2.5-fold better (P=0.02) for the controls. By day 34 the overall positive effect (i.e. healing and improvement) was 1.75-fold better (P=0.05) for the treatment group. Lesions from the control group were 2.2 times more likely (P=0.09) to have a pain score equal to 2 by day 14. The proportion of lesions getting smaller by days 14 and 34 was 2.5 times higher (P<0.08) for the treatment vs. the control group. The findings suggest salicylic acid should be considered as an alternative to chlortetracycline for the treatment of DD as it appears more efficacious and would assist in reducing antibiotic use.

  4. Identifying predictive clinical characteristics of the treatment efficacy of mirtazapine monotherapy for major depressive disorder

    PubMed Central

    Tsutsumi, Takahiro; Sugawara, Hiroko; Ito, Ryoko; Asano, Mizuho; Shimizu, Satoru; Ishigooka, Jun; Nishimura, Katsuji

    2016-01-01

    Background Mirtazapine, which is classified as a noradrenergic and specific serotonergic antidepressant, is widely prescribed for the treatment of major depressive disorder. The potential predictive factors of the efficacy of mirtazapine and the tolerability based on the incidence of oversedation and jitteriness/anxiety syndrome were evaluated. Patients and methods Patients with major depressive disorder were retrospectively investigated. Study subjects comprised 68 patients with depression who received mirtazapine as an initial antidepressant at the Department of Psychiatry of the Tokyo Women’s Medical University Hospital from September 2009 to March 2013. The efficacy of mirtazapine monotherapy was evaluated based on the Clinical Global Impression Improvement score. Clinical characteristics were compared between remission and nonremission groups to determine the factors predicting the efficacy. Moreover, discontinuation rates due to adverse effects, including oversedation and jitteriness/anxiety syndrome, were examined, and the effects of confounding factors were evaluated. Results The remission rate of mirtazapine monotherapy was 36.8% among the 68 enrolled subjects. The mean final doses in the remission and nonremission groups were 27.6±13.5 mg and 26.0±14.1 mg, respectively, and there was no significant difference between them. Multiple logistic analyses revealed that the absence of guilt (odds ratio [OR] =0.15; 95% CI [1.66–37.24], P=0.006) and the presence of psychomotor retardation (OR =4.30; 95% CI [1.30–16.60], P=0.016) were significantly related to the efficacy of mirtazapine monotherapy. The discontinuation rates due to oversedation and jitteriness/anxiety syndrome were 13.2% and 11.8%, respectively. Age did not differ significantly between patients with or without oversedation or jitteriness/anxiety syndrome (P=0.078 and P=0.579, respectively). Conclusion The absence of guilt and the presence of psychomotor retardation may predict the efficacy

  5. Comparison of efficacy and safety of oseltamivir and zanamivir in pandemic influenza treatment

    PubMed Central

    Tuna, Nazan; Karabay, Oguz; Yahyaoğlu, Mehmet

    2012-01-01

    Aim: In 2009, a flu pandemic caused panic worldwide. Oseltamivir and zanamivir were widely used in this pandemic. Currently, there are a limited number of studies comparing the efficacy and tolerability of these two drugs. This study aimed to compare the efficacy and tolerability of these two drugs in the treatment of influenza. Materials and Methods: Patients diagnosed with influenza at our infectious disease outpatient clinic during the influenza season between October 1, 2009 and February 1, 2010 were included in the study. Study data were obtained retrospectively from files for consecutive patients. A total of 136 subjects were selected. After exclusion criteria were applied, 56 subjects were discarded. The information for 80 patients in whom oseltamivir or zanamivir therapy was initiated (40 for each therapy) was compiled, and the efficacy and tolerability of the drugs were compared. Results: There was no significant difference in efficacy for the two drugs (P > 0.05). Temperature normalization was significantly faster in patients taking zanamivir (P = 0.0157). Drowsiness was the most frequent adverse event for both drugs (38% for the oseltamivir group, and 22% for the zanamivir group). Respiratory distress was observed in five patients in the zanamivir group, whereas it was not observed in patients in the oseltamivir group (P < 0.05). One patient had to discontinue therapy in the zanamivir group due to respiratory distress. Conclusion: Efficacy (in terms of symptom relief and duration to resumption of work) and adverse events were similar for zanamivir and oseltamivir, but temperature normalization was much more rapid in patients using zanamivir. Patients using zanamivir should be monitored for respiratory distress. PMID:23248411

  6. Efficacy of weekly paclitaxel treatment as a single agent chemotherapy following first-line cisplatin treatment in urothelial bladder cancer

    PubMed Central

    SIDERIS, SPYRIDON; AOUN, FOUAD; ZANATY, MARC; MARTINEZ, NIEVES CHANZA; LATIFYAN, SOFIA; AWADA, AHMAD; GIL, THIERRY

    2016-01-01

    The aim of the present study was to investigate the efficacy of paclitaxel following a first-line cisplatin regimen in patients with metastatic bladder cancer. The present study retrospectively evaluated the clinical effects and toxicities of second-line paclitaxel regimens following first-line cisplatin treatment in metastatic bladder cancer. A total of 42 patients with progressing metastatic urothelial bladder cancer following cisplatin-based chemotherapy were enrolled. The patients received weekly treatment with paclitaxel (80 mg/m2) with a median duration of 3 months. The overall response rate, disease control rate and median progression free survival were 9.5, 45.2 and 6.4 months, respectively. Weekly paclitaxel was well-tolerated with rare grade III or IV toxicities. Second-line weekly paclitaxel treatment following first-line cisplatin-based chemotherapy is an effective and well-tolerated regimen in urothelial metastatic bladder cancer. PMID:27284445

  7. Neurosurgical delivery of chemotherapeutics, targeted toxins, genetic and viral therapies in neuro-oncology.

    PubMed

    Chiocca, E Antonio; Broaddus, William C; Gillies, George T; Visted, Therese; Lamfers, Martine L M

    2004-01-01

    Local delivery of biologic agents, such as gene and viruses, has been tested preclinically with encouraging success, and in some instances clinical trials have also been performed. In addition, the positive pressure infusion of various therapeutic agents is undergoing human testing and approval has already been granted for routine clinical use of biodegradable implants that diffuse a chemotherapeutic agent into peritumoral regions. Safety in glioma patients has been shown, but anticancer efficacy needs additional refinements in the technologies employed. In this review, we will describe these modalities and provide a perspective on needed improvements that should render them more successful.

  8. Discovery and SAR of orally efficacious tetrahydropyridopyridazinone PARP inhibitors for the treatment of cancer.

    PubMed

    Zhu, Gui-Dong; Gong, Jianchun; Gandhi, Viraj B; Liu, Xuesong; Shi, Yan; Johnson, Eric F; Donawho, Cherrie K; Ellis, Paul A; Bouska, Jennifer J; Osterling, Donald J; Olson, Amanda M; Park, Chang; Luo, Yan; Shoemaker, Alexander; Giranda, Vincent L; Penning, Thomas D

    2012-08-01

    PARP-1, the most abundant member of the PARP superfamily of nuclear enzymes, has emerged as a promising molecular target in the past decade particularly for the treatment of cancer. A number of PARP-1 inhibitors, including veliparab discovered at Abbott, have advanced into different stages of clinical trials. Herein we describe the development of a new tetrahydropyridopyridazinone series of PARP-1 inhibitors. Many compounds in this class, such as 20w, displayed excellent potency against the PARP-1 enzyme with a K(i) value of <1nM and an EC(50) value of 1nM in a C41 whole cell assay. The presence of the NH in the tetrahydropyridyl ring of the tetrahydropyridopyridazinone scaffold improved the pharmacokinetic properties over similar carbon based analogs. Compounds 8c and 20u are orally available, and have demonstrated significant efficacy in a B16 murine xenograft model, potentiating the efficacy of temozolomide (TMZ).

  9. Efficacy of aloe vera cream in prevention and treatment of sunburn and suntan.

    PubMed

    Puvabanditsin, Porntip; Vongtongsri, Rujirat

    2005-09-01

    The efficacy of aloe vera cream in prevention of burn and tan from ultraviolet were studied in 20 volunteers. The minimal erythema dose of 20 volunteers were tested. The mean MED was 40-60 mj. The well preserved containing 70% of aloe vera cream. The aloe vera cream was applied randomized double blind technique on the test sites 30 minutes before, immediately after, or both before and after then the serial ultraviolet UVB 40,50,60,70,80 mj were radiated. MED reading at 24 hour for sunburn evaluation. Erythema and pigmentation were evaluated by visual grading 1-4 score. The aloe vera cream was continuing applied at the test sites twice daily for the the next three weeks. The results showed that the aloe vera cream has no sunburn or suntan protection and no efficacy in sunburn treatment when compared to placebo. The aloe vera cream has no bleaching effect too.

  10. Efficacy of Fifteen Emerging Interventions for the Treatment of Posttraumatic Stress Disorder: A Systematic Review.

    PubMed

    Metcalf, Olivia; Varker, Tracey; Forbes, David; Phelps, Andrea; Dell, Lisa; DiBattista, Ashley; Ralph, Naomi; O'Donnell, Meaghan

    2016-02-01

    Although there is an abundance of novel interventions for the treatment of posttraumatic stress disorder (PTSD), often their efficacy remains unknown. This systematic review assessed the evidence for 15 new or novel interventions for the treatment of PTSD. Studies that investigated changes to PTSD symptoms following the delivery of any 1 of the 15 interventions of interest were identified through systematic literature searches. There were 19 studies that met the inclusion criteria for this study. Eligible studies were assessed against methodological quality criteria and data were extracted. The majority of the 19 studies were of poor quality, hampered by methodological limitations, such as small sample sizes and lack of control group. There were 4 interventions, however, stemming from a mind-body philosophy (acupuncture, emotional freedom technique, mantra-based meditation, and yoga) that had moderate quality evidence from mostly small- to moderate-sized randomized controlled trials. The active components, however, of these promising emerging interventions and how they related to or were distinct from established treatments remain unclear. The majority of emerging interventions for the treatment of PTSD currently have an insufficient level of evidence supporting their efficacy, despite their increasing popularity. Further well-designed controlled trials of emerging interventions for PTSD are required. PMID:26749196

  11. Comparison of clinical efficacies of sodium ascorbyl phosphate, retinol and their combination in acne treatment.

    PubMed

    Ruamrak, C; Lourith, N; Natakankitkul, S

    2009-02-01

    Acne vulgaris impairs the appearance of an individual and causes psychological irritation. Inflammatory acne lesion is caused by multifactor incorporates in each step of acne pathogenesis. In an attempt to archive inflammatory lesion treatment with the promise of prevention of acne vulgaris, randomized and double-blind studies on the comparison of the efficacies of topical formulations containing 5% sodium ascorbyl phosphate (SAP) and 0.2% retinol, separately as well as in combination application, were conducted. The resulting data showed that SAP reduced the inflammatory lesion by 20.14% and 48.82% within 4 and 8 weeks respectively. Application of the formulation containing retinol slightly improved the treatment efficacy as the lesion reduced by 21.79% and 49.50% after 4 and 8 weeks respectively. The combination treatment significantly reduced the inflammatory lesion by 29.28% after 4 weeks and 63.10% after 8 weeks of application. The most effective treatment was by using the combination of 5% SAP and 0.2% retinol, which incorporated the synergistic effects on lipid peroxidation and sebaceous gland function in addition to the enhancement of SAP permeability by the desquamation of stratum corneum influenced by retinol, keratin plug removal and anti-inflammatory effect of retinol. This study promises for the development of cosmetic products to overcome aesthetic and psychological problems caused by acne vulgaris. PMID:19134126

  12. Treatment of Chronic Migraine with OnabotulinumtoxinA: Mode of Action, Efficacy and Safety

    PubMed Central

    Szok, Délia; Csáti, Anett; Vécsei, László; Tajti, János

    2015-01-01

    Background: Chronic migraine is a common, highly disabling, underdiagnosed and undertreated entity of migraine. It affects 0.9%–2.2% of the general adult population. The present paper overviews the preclinical and clinical data regarding the therapeutic effect of onabotulinumtoxinA in chronic migraineurs. Methods: A literature search was conducted in the database of PubMed up to 20 May 2015 for articles related to the pathomechanism of chronic migraine, the mode of action, and the efficacy, safety and tolerability of onabotulinumtoxinA for the preventive treatment of chronic migraine. Results: The pathomechanism of chronic migraine has not been fully elucidated. The mode of action of onabotulinumtoxinA in the treatment of chronic migraine is suggested to be related to the inhibition of the release of calcitonin gene-related peptide and substance P in the trigeminovascular system. Randomized clinical trials demonstrated that long-term onabotulinumtoxinA fixed-site and fixed-dose (155–195 U) intramuscular injection therapy was effective and well tolerated for the prophylactic treatment of chronic migraine. Conclusions: Chronic migraine is a highly devastating entity of migraine. Its exact pathomechanism is unrevealed. Two-third of chronic migraineurs do not receive proper preventive medication. Recent clinical studies revealed that onabotulinumtoxinA was an efficacious and safe treatment for chronic migraine. PMID:26193319

  13. Treatment Research for Trauma/PTSD in Youth and Adults: Moving from Efficacy to Effectiveness

    PubMed Central

    Kolko, David J.; Hoagwood, Kimberly Eaton; Springgate, Benjamin

    2010-01-01

    Objective Population-based demands for trauma services have accelerated interest in rapid deployment of efficacious interventions to address the diverse mental health consequences of traumatic experiences. However, optimal strategies for supporting either implementation or dissemination of trauma-focused interventions within healthcare or mental healthcare systems are under developed. Methods This paper offers suggestions for adapting treatment research parameters in order to advance the science on the implementable and practical use of trauma-focused interventions within a public health framework. To this end, we briefly examine the current status of the research evidence in this area and discuss efficacy and effectiveness treatment research parameters with specific attention to the implications for developing the research base on implementation and dissemination of effective trauma practices for children. Results Examples from current studies are used to identify approaches for developing, testing, and enhancing strategies to roll-out effective treatment practices in real-world settings. Conclusions New approaches that reflect the contexts in which these practices are implemented may enhance the feasibility, acceptability, replicability, and sustainability of trauma treatments and services and thus improve outcomes for a broader population of youth and families. PMID:20851266

  14. Efficacy and effect of free treatment on multidrug-resistant tuberculosis

    PubMed Central

    ZHANG, QING; WU, ZHEYUAN; ZHANG, ZURONG; SHA, WEI; SHEN, XIN; XIAO, HEPING

    2016-01-01

    Multidrug-resistant tuberculosis (MDR-TB) is a serious public health and social issue. It pertains to the type of tuberculosis that is resistant simultaneously to isoniazid and rifampicin. MDR-TB has a high mortality and is expensive to treat. The aim of the present study was to examine the therapeutic effects of individualized free treatment and the relevant influencing factors on the treatment outcome for MDR-TB. A prospective study module was used to analyze the therapeutic outcome of MDR-TB with individualized free treatment for 160 patients between 2011 and 2014. Statistical analysis was performed using the Chi-square or Fisher's exact test, and the odds ratio was calculated using a logistic regression analysis model. In total, 160 patients were enrolled in the study for treatment of MDR-TB. From these, 88 cases completed the course of treatment, and 70 cases were successfully treated. Of the remaining 72 cases, 37 cases exhibited treatment failure, 18 cases were suspended during treatment and 17 patients succumbed to the disease. The results showed that the confounding factors were: i) retreatment (p<0.05); ii) occurrence of diabetes (p<0.001); iii) lesion without improvement in radiography during treatment (p=0.001); iv) positive sputum culture for Mycobacterium tuberculosis after 3-month treatment (p<0.05); and v) termination of treatment due to adverse reaction (p<0.05). These factors were associated with poor treatment outcomes by logistic regression analysis. Adverse drug reaction was observed in 33 cases and treatment was terminated or changed permanently in 29 of these cases. The most common adverse reaction was liver function damage caused by pyrazinamide and leucopenia caused by rifabutin. One patient suffered from serious liver failure. In conclusion, the success rate of long treatment course for MDR-TB is not high due to many adverse reactions. Occurrence of diabetes is the main factor that caused poor efficacy. PMID:26997992

  15. Comparative efficacy of various treatment regimens for androgenetic alopecia in men.

    PubMed

    Khandpur, Sujay; Suman, Mansi; Reddy, Belum Sivanagi

    2002-08-01

    Our understanding of the aetiology of androgenetic alopecia (AGA) has substantially increased in recent years. As a result, several treatment modalities have been tried with promising results especially in early stages of AGA. However, as far as has been ascertained, there is no comprehensive study comparing the efficacy of these agents alone and in combination with each other. One hundered male patients with AGA of Hamilton grades II to IV were enrolled in an open, randomized, parallel-group study, designed to evaluate and compare the efficacy of oral finasteride (1 mg per day), topical 2% minoxidil solution and topical 2% ketoconazole shampoo alone and in combination. They were randomized into four groups. Group I (30 patients) was administered oral finasteride, Group II (36 patients) was given a combination of finasteride and topical minoxidil, Group III (24 patients) applied minoxidil alone and Group IV (10 patients) was administered finasteride with topical ketoconazole. Treatment efficacy was assessed on the basis of patient and physician assessment scores and global photographic review during the study period of one year. At the end of one year, hair growth was observed in all the groups with best results recorded with a combination of finasteride and minoxidil (Group II) followed by groups IV, I and III. Subjects receiving finasteride alone or in combination with minoxidil or ketoconazole showed statistically significant improvement (p<0.05) over minoxidil only recipients. No signifcant side-effects related to the drugs were observed. In conclusion, it is inferred that the therapeutic efficacy is enhanced by combining the two drugs acting on different aetiological aspects of AGA. PMID:12227482

  16. Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax

    PubMed Central

    Tamayo Perez, María-Eulalia; Aguirre-Acevedo, Daniel Camilo

    2015-01-01

    Objective: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. Methods: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. Results: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow-up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. Conclusion: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax. PMID:26848199

  17. Ovicidal efficacy of fenbendazole after treatment of horses naturally infected with cyathostomins.

    PubMed

    Daniels, S P; Proudman, C J

    2016-08-30

    The ovicidal activity of benzimidazole (BZ) anthelmintics is unique and not seen in other drug classes. Such ovicidal efficacy is not widely reported for equine cyathostomins, nor has this activity been tested in the face of BZ resistance. Although the product label states that fenbendazole is for use against BZ-susceptible cyathostomins, susceptibility testing is rarely performed. In this field-based study, the ovicidal efficacy of fenbendazole in horses (n=39) harbouring BZ-resistant cyathostomins was compared when dosed at 7.5mg/kg body weight (BW) orally, as a single dose per os (n=21) or daily for five consecutive days in feed (n=18). Suppression of egg hatch rate was observed in the single and five- day treatment groups; a significant difference between pre- and post-treatment egg hatch rates (P<0.05) was observed for three days after treatment with a single dose of fenbendazole (on premises with BZ-resistant cyathostomins), and for three days after treatment for five consecutive days with fenbendazole (on premises with BZ-resistant cyathostomins). Post treatment numbers of eggs and larvae remained significantly lower (P<0.05) than pre-treatment levels to the end of the trial. We conclude that in the face of BZ-resistant cyathostomins the ovicidal effect of fenbendazole persist for three days after both a single oral dose of 7.5mg/kg per os and after treatment orally for five consecutive daily doses at 7.5mg/kg in feed. PMID:27523952

  18. Ovicidal efficacy of fenbendazole after treatment of horses naturally infected with cyathostomins.

    PubMed

    Daniels, S P; Proudman, C J

    2016-08-30

    The ovicidal activity of benzimidazole (BZ) anthelmintics is unique and not seen in other drug classes. Such ovicidal efficacy is not widely reported for equine cyathostomins, nor has this activity been tested in the face of BZ resistance. Although the product label states that fenbendazole is for use against BZ-susceptible cyathostomins, susceptibility testing is rarely performed. In this field-based study, the ovicidal efficacy of fenbendazole in horses (n=39) harbouring BZ-resistant cyathostomins was compared when dosed at 7.5mg/kg body weight (BW) orally, as a single dose per os (n=21) or daily for five consecutive days in feed (n=18). Suppression of egg hatch rate was observed in the single and five- day treatment groups; a significant difference between pre- and post-treatment egg hatch rates (P<0.05) was observed for three days after treatment with a single dose of fenbendazole (on premises with BZ-resistant cyathostomins), and for three days after treatment for five consecutive days with fenbendazole (on premises with BZ-resistant cyathostomins). Post treatment numbers of eggs and larvae remained significantly lower (P<0.05) than pre-treatment levels to the end of the trial. We conclude that in the face of BZ-resistant cyathostomins the ovicidal effect of fenbendazole persist for three days after both a single oral dose of 7.5mg/kg per os and after treatment orally for five consecutive daily doses at 7.5mg/kg in feed.

  19. One-Session Treatment of Specific Phobias: A Detailed Description and Review of Treatment Efficacy

    ERIC Educational Resources Information Center

    Zlomke, Kimberly; Davis, Thompson E., III

    2008-01-01

    One-Session Treatment (OST) is a form of massed exposure therapy for the treatment of specific phobias. OST combines exposure, participant modeling, cognitive challenges, and reinforcement in a single session, maximized to three hours. Clients are gradually exposed to steps of their fear hierarchy using therapist-directed behavioral experiments.…

  20. Coping and Self-Efficacy in Marijuana Treatment: Results from the Marijuana Treatment Project

    ERIC Educational Resources Information Center

    Litt, Mark D.; Kadden, Ronald M.; Stephens, Robert S.

    2005-01-01

    This study examined whether a coping-skills-based treatment for marijuana dependence operated by encouraging the use of coping skills or via other mechanisms. Participants were 450 men and women treated in the multisite Marijuana Treatment Project who were randomly assigned to motivational enhancement therapy plus cognitive-behavioral (MET-CB)…

  1. Chemotherapeutic Drugs Interfere with Gene Delivery Mediated by Chitosan-Graft-Poly(ethylenimine).

    PubMed

    Lai, Wing-Fu; Lin, Marie C

    2015-01-01

    Combined chemo-gene therapy is one of the treatment modalities that have attracted extensive research interests; however, there is little information regarding the influence of drug application on gene transfer. This study bridges this gap by examining how chemotherapeutic drugs (teniposide, cis-diamminedichloroplatinum(II) and temozolomide) interfere with polyplex formation and transfection of chitosan-graft-poly(ethylenimine). Our results indicate that the degree of drug interference varies with the mechanism of drug action, with the transgene expression being severely suppressed when the plasmid is co-delivered with cis-diamminedichloroplatinum(II) or teniposide but not temozolomide. In addition, the interference with transfection by drugs varies with different gene/drug co-formulations. This is the first study to evidence that, though combined chemo-gene therapy has therapeutic potential, some chemotherapeutic drugs may reduce the treatment efficiency of gene therapy. PMID:25961282

  2. [Review of the clinical efficacy of flutrimazole gel in the treatment of dandruff and/or seborrheic dermatitis.].

    PubMed

    Noguera, J; Lerís, E; Algueró, M; Boncompte, E; Izquierdo, I

    1998-03-01

    The purpose of this article is to review the phase II and phase III clinical trials with the new pharmaceutical gel form of flutrimazole. The aim of the phase II study was to determine the efficacy and tolerance of flutrimazole 1%, 2% and 4% gel when compared to placebo in the treatment of 80 patients with dandruff or seborrheic dermatitis at a dose of three applications per week during one month. Flutrimazole 1% gel had a similar efficacy compared to the other studied concentrations and a superior efficacy when compared to placebo (p < 0.05). All treatments studied had an excellent tolerance. In the phase III study, the efficacy and tolerance of flutrimazole 1% gel was compared to ketoconazole 2% gel in 192 patients with dandruff or seborrheic dermatitis. Flutrimazole gel had a similar efficacy to ketoconazole gel at a dose of three applications per week for 28 days. Both products were well tolerated and no adverse effects were recorded. PMID:17655401

  3. Efficacy of water treatment processes and endemic gastrointestinal illness - A multi-city study in Sweden.

    PubMed

    Tornevi, Andreas; Simonsson, Magnus; Forsberg, Bertil; Säve-Söderbergh, Melle; Toljander, Jonas

    2016-10-01

    Outbreaks of acute gastrointestinal illnesses (AGI) have been linked to insufficient drinking water treatment on numerous occasions in the industrialized world, but it is largely unknown to what extent public drinking water influences the endemic level of AGI. This paper aimed to examine endemic AGI and the relationship with pathogen elimination efficacy in public drinking water treatment processes. For this reason, time series data of all telephone calls to the Swedish National Healthcare Guide between November 2007 and February 2014 from twenty Swedish cities were obtained. Calls concerning vomiting, diarrhea or abdominal pain (AGI calls) were separated from other concerns (non-AGI calls). Information on which type of microbial barriers each drinking water treatment plant in these cities have been used were obtained, together with the barriers' theoretical pathogen log reduction efficacy. The total log reduction in the drinking water plants varied between 0.0 and 6.1 units for viruses, 0.0-14.6 units for bacteria and 0.0-7.3 units regarding protozoans. To achieve one general efficacy parameter for each plant, a weighted mean value of the log reductions (WLR) was calculated, with the weights based on how commonly these pathogen groups cause AGI. The WLR in the plants varied between 0.0 and 6.4 units. The effect of different pathogen elimination efficacy on levels of AGI calls relative non-AGI calls was evaluated in regression models, controlling for long term trends, population size, age distribution, and climatological area. Populations receiving drinking water produced with higher total log reduction was associated with a lower relative number of AGI calls. In overall, AGI calls decreased by 4% (OR = 0.96, CI: 0.96-0.97) for each unit increase in the WLR. The findings apply to both groundwater and surface water study sites, but are particularly evident among surface water sites during seasons when viruses are the main cause of AGI. This study proposes that the

  4. The Efficacy of Eye Movement Desensitization and Reprocessing Therapy Technique in the Treatment of Test Anxiety of College Students.

    ERIC Educational Resources Information Center

    Enright, Matthew; Baldo, Tracy D.; Wykes, Scott D.

    2000-01-01

    Explores the efficacy of eye movement desensitization and reprocessing (EMDR) in the treatment of test anxiety. Thirty-five college students with test anxiety were assigned to either a treatment or delayed treatment control group. EMDR was shown to be effective in reducing overall test anxiety as well as "emotionality" and "worry" components of…

  5. Old drugs, novel ways out: Drug resistance toward cytotoxic chemotherapeutics.

    PubMed

    Wijdeven, Ruud H; Pang, Baoxu; Assaraf, Yehuda G; Neefjes, Jacques

    2016-09-01

    Efficacy of chemotherapy in the treatment of distinct malignancies is often hampered by drug resistance arising in the tumor. Understanding the molecular basis of drug resistance and translating this knowledge into personalized treatment decisions can enhance therapeutic efficacy and even curative outcome. Over the years, multiple drug resistance mechanisms have been identified that enable tumors to cope with the damage instigated by a specific drug or group of anti-tumor agents. Here we provide an overview of the molecular pathways leading to resistance against conventional anti-cancer drugs, with emphasis on the utility of these pathways for rational selection of treatments for individual cancer patients. We further complement the review by discussing the pitfalls and difficulties in translating these findings into novel treatment strategies for cancer patients. PMID:27620955

  6. Treatment of infestation with Phthirus pubis: comparative efficacies of synergized pyrethrins and gamma-benzene hexachloride.

    PubMed

    Newsom, J H; Fiore, J L; Hackett, E

    1979-01-01

    In recent years there has been a steady increase in the incidence of infestation with Phthirus pubis, a sexually transmitted louse. A recently introduced nonprescription liquid pediculicide, whose major ingredient is 0.3% pyrethrins synergized by 3.0% piperonyl butoxide (RiD), was compared for efficacy and safety with a prescription-only pediculicidal lotion whose major ingredient is 1% gamma-benzene hexachloride (Kwell). Thirty adult man and women with P. pubis infestation were assigned randomly to treatment with either the synergized pyrethrins or gamma-benzene hexachloride. A single 10-min application of the synergized-pyrethrin liquid produced the same results as a single 12-hr application of the gamma-benze hexachloride lotion: total eradication of adult lice and nymphs, cessation of pruritus, and no treatment-induced side effect. A follow-up visit a week after treatment verified all eradications.

  7. Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference

    PubMed Central

    Naegel, Steffen; Obermann, Mark

    2010-01-01

    Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and/or the presence of aura. Considerable advances have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. Unfortunately, preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. Topiramate is an antipileptic drug with a complex mode of action which has proven its efficacy and safety in the prophylactic treatment of episodic migraine in a number of randomized controlled clinical trials. Topiramate is also effective in treating patients with chronic migraine. It has little pharmacological interaction with other drugs and is generally well tolerated by patients. PMID:20169042

  8. Safety and Efficacy of Cyclosporine in the Treatment of Chronic Dry Eye

    PubMed Central

    Schultz, Clyde

    2014-01-01

    Dry-eye syndrome (DES) is a multifactorial disease affecting millions of individuals worldwide. Various factors, including age, hormonal status, genetics, sex, immune status, innervation status, nutrition, pathogens, and environmental stress, can alter the cellular and molecular structure or function of components of the ocular surface system. The resulting imbalance increases susceptibility to desiccation and epithelial damage, leading to a vicious circle in which inflammation amplifies and sustains further damage by chronic deregulation of the system. Lubricating agents and steroids have been used as treatment options. However, as the causes of the disease become better elucidated, the more chemically complex cyclosporine A has become an increasingly useful treatment option and in the United States is currently the only Food and Drug Administration (FDA)-approved prescription drug for the treatment of dry eye. The safety and efficacy of cyclosporine have been shown in numerous studies. PMID:25002818

  9. Efficacy of platelet-rich plasma in treatment of androgenic alopecia

    PubMed Central

    Singhal, Parul; Agarwal, Sachin; Dhot, Paramjeet Singh; Sayal, Satish K.

    2015-01-01

    Background: Platelet-rich plasma (PRP) has shown remarkable beneficial effects without any major adverse reactions in the treatment of androgenic alopecia. The growth factors in activated autologous PRP induce the proliferation of dermal papilla cells. Objectives: The objective was to investigate the clinical efficacy of PRP in treatment of androgenic alopecia. Materials and Methods: Ten patients were given autologous PRP injections on the affected area of alopecia over a period of 3 months at interval of 2-3 weeks and results were assessed. Results: Three months after the treatment, the patients presented clinical improvement in the hair counts, hair thickness, hair root strength, and overall alopecia. Conclusion: PRP appears to be a cheap, effective, and promising therapy for androgenic alopecia with no major adverse effects. PMID:26420936

  10. From efficacy to effectiveness: the trajectory of the treatment literature for children with PTSD.

    PubMed

    Nikulina, Valentina; Hergenrother, Jeanean M; Brown, Elissa J; Doyle, Megan E; Filton, Beryl J; Carson, Gabrielle S

    2008-08-01

    This review summarizes efficacious treatments for preschoolers, children and adolescents with post-traumatic stress disorder, with a focus on the advances made within the last 5 years. There is considerable support for the use of trauma-specific cognitive-behavioral interventions, in both individual and group formats. The research on psychopharmacological treatments lags behind that of psychotherapy and is currently inconclusive. Limitations of the studies are discussed and treatments that warrant further consideration are reviewed. The authors also review current advances in effectiveness and suggest future directions that are important in generalizing the interventions to underserved and hard to reach populations. The article concludes with the authors' projections for the evolution of the field within the upcoming 5 years.

  11. The Efficacy of 100 and 300 mg Gabapentin in the Treatment of Carpal Tunnel Syndrome.

    PubMed

    Eftekharsadat, Bina; Babaei-Ghazani, Arash; Habibzadeh, Afshin

    2015-01-01

    Carpal tunnel syndrome (CTS) is a neuropathy due to the compression of the median nerve. It is shown that gabapentin in high doses is effective in treatment of CTS patients. In this study we evaluated the efficacy of low doses of gabapentin in treatment of CTS patients. Ninety patients with CTS were randomly assigned to groups A, B and C. Gabapentin was administered to group A with dose of 100 mg/day and to group B with dose of 300 mg/day for 2 months. Group C received no treatment. Before and after treatment, patients were evaluated using Visual analogue scale (VAS) for pain and parasthesia, Boston carpal tunnel questionnaire (BCTQ) including Symptom Severity Scale (SSS) and Functional Status Scale (FSS) to evaluate the efficacy of the treatment. The pinch and grip strength was also measured. There was significant improvement in VAS, grip strength, pinch strength, SSS, FSS and BCTQ score in all three groups (p < 0.05), but the changes in CMAP and SNAP was not significant. Groups A and B in comparison to group C had significantly better improvement in VAS, pinch strength, SSS, FSS and BCTQ total score (p < 0.05). There was significantly more improvement in pinch strength and SSS score in group B compared to group A (p < 0.05). Gabapentin in low doses is a useful drug in treatment of CTS symptoms with no side effects and intolerance. Gabapentin with dose of 300 mg/day is more effective than the dose of 100 mg/day. PMID:26664397

  12. Efficacy of contingency management for cocaine dependence treatment: a review of the evidence.

    PubMed

    Schierenberg, Alwin; van Amsterdam, Jan; van den Brink, Wim; Goudriaan, Anna E

    2012-12-01

    Cocaine dependence causes serious individual and social harm and a considerable proportion of substance related treatment capacity is devoted to cocaine dependent persons. In the absence of approved pharmacotherapies, other treatments for cocaine dependence should be explored. In this review, the efficacy of Contingency Management (CM), a promising behavior therapy using operant conditioning, is evaluated for the treatment of cocaine dependence. A systematic evaluation of 19 studies with a total of 1,664 patients showed that CM - in combination with standard cognitive behavioral or other psychological interventions - (1) increases cocaine abstinence, (2) improves treatment retention during and after group-based or individual psychological treatment, (3) is of benefit in pharmacotherapy trials, and (4) that CM may act synergistically with pharmacotherapy. This suggests that CM is a promising add-on intervention for cocaine dependence treatment. Therefore, it is advocated to include CM in standard treatment programs for cocaine dependence and future pharmacotherapy research. Future larger studies are deemed necessary to replicate these promising results, now often lacking statistical significance.

  13. Pilot evaluation of the efficacy of shampoo treatment with ultrapure soft water for canine pruritus.

    PubMed

    Ohmori, Keitaro; Tanaka, Akane; Makita, Yuka; Takai, Masaki; Yoshinari, Yuji; Matsuda, Hiroshi

    2010-10-01

    Ultrapure soft water (UPSW) is water in which calcium and magnesium ions have been replaced with sodium ions using a cation-exchange resin. We recently demonstrated that washing with soap and UPSW reduced the clinical severity of dermatitis and improved the skin barrier function in NC/NgaTnd mice, a murine model for human atopic dermatitis. The purpose of this pilot study was to evaluate the efficacy of shampoo treatment with UPSW for dogs with pruritus. Eleven dogs with pruritus were randomly assigned to two groups depending on whether they received weekly shampoo treatment with UPSW or tap water for 4 weeks. After a washout period, the treatment protocol was switched such that each dog received both treatments. The pre-treatment and post-treatment values of the following were compared: pruritus scores assessed by the owners; dermatitis scores recorded by an investigator; and transepidermal water loss (TEWL). Shampoo treatment with UPSW significantly decreased pruritus and dermatitis scores in the dogs, whereas shampoo treatment with tap water did not. In addition, shampoo treatment with UPSW, but not with tap water, significantly reduced TEWL in the dogs. Adverse events due to the treatment were not observed in the dogs. Furthermore, we found that topical application of UPSW for barrier-disrupted skin caused by tape stripping in healthy dogs decreased TEWL more rapidly than topical application of tap water. Our findings suggest that shampoo treatment with UPSW promotes skin barrier recovery and thus could be considered as a possible therapeutic option in the management of pruritus and dermatitis in dogs.

  14. Evaluating the safety and efficacy of dextromethorphan/quinidine in the treatment of pseudobulbar affect

    PubMed Central

    Schoedel, Kerri A; Morrow, Sarah A; Sellers, Edward M

    2014-01-01

    Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, multiple sclerosis, Parkinson’s disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration–effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug’s side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients

  15. The effect of seasonal temperature on pathogen removal efficacy of vermifilter for wastewater treatment.

    PubMed

    Arora, Sudipti; Kazmi, A A

    2015-05-01

    The present study explored the effects of seasonal temperature on the treatment efficiency and pathogen removal efficacy from synthetic domestic wastewater, earthworm population characteristics and microbial population in the filter media of a lab-scale vermifilter (VF). The experimental phase lasted for one year and daily mean room temperature showed a difference of 2-16 °C between winter (Dec-Feb), spring (Mar-May), summer (Jun-Aug) and autumn (Sep-Nov) periods. The results showed that variation in ambient temperature had a significant effect on chemical oxygen demand (COD) and biochemical oxygen demand (BOD) reduction, indicator organisms and pathogen removal, earthworm population, bacterial and actinomycetes number, but had no effect on total suspended solids (TSS) removal and fungi number. The study showed that higher BOD and COD removal was accomplished during the spring and autumn period when the mean temperature was 25-27 °C. This temperature range is optimum for the earthworm species Eisenia fetida for its activity, growth and reproduction and any variation in temperature from the optimum range led to decrease in treatment efficiency and earthworm population. However, during summer, when the maximum temperature reached 38-40 °C, the indicator bacteria removal was maximum by 99.9%, Salmonella reduction by 96.9% and Escherichia coli by 99.3%. The pathogen removal efficacy of VF increases with the increase in temperature, as shown by linear regression analysis, which implied that temperature had a significant contribution to the pathogen removal efficiency of VF. Pearson coefficient of correlation (r) derived an important relationship between the seasonal temperature and treatment efficiency, pathogen removal efficacy and microbial numbers during vermifiltration. PMID:25720670

  16. Efficacy of Percutaneous Adhesiolysis in the Treatment of Lumbar Post Surgery Syndrome

    PubMed Central

    Manchikanti, Laxmaiah; Manchikanti, Kavita N.; Gharibo, Christopher G.; Kaye, Alan D.

    2016-01-01

    Context Lumbar post-surgery syndrome is common and often results in chronic, persistent pain and disability, which can lead to multiple interventions. After failure of conservative treatment, either surgical treatment or a nonsurgical modality of treatment such as epidural injections, percutaneous adhesiolysis is often contemplated in managing lumbar post surgery syndrome. Recent guidelines and systematic reviews have reached different conclusions about the level of evidence for the efficacy of epidural injections and percutaneous adhesiolysis in managing lumbar post surgery syndrome. The objective of this systematic review was to determine the efficacy of all 3 percutaneous adhesiolysis anatomical approaches (caudal, interlaminar, and transforaminal) in treating lumbar post-surgery syndrome. Evidence Acquisition Data Sources: A literature search was performed from 1966 through October 2014 utilizing multiple databases. Study Selection: A systematic review of randomized trials published from 1966 through October 2014 of all types of epidural injections and percutaneous adhesiolysis in managing lumbar post-surgery syndrome was performed including methodological quality assessment utilizing Cochrane review criteria, Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment (IPM–QRB), and grading of evidence using 5 levels of evidence ranging from Level I to Level V. Data Extraction: The search strategy emphasized post-surgery syndrome and related pathologies treated with percutaneous adhesiolysis procedures. Results The search criteria yielded 16 manuscripts on percutaneous adhesiolysis assessing post-surgery syndrome. Of these, only 4 randomized trials met inclusion criteria for methodological quality assessment, 3 of them were of high quality; and the fourth manuscript was of low quality. Based on these 3 randomized controlled trials, 2 of them with one-day procedure and one with a 3-day procedure, the level of

  17. Efficacy of different treatment regimens of marbofloxacin in canine visceral leishmaniosis: a pilot study.

    PubMed

    Rougier, Sandrine; Vouldoukis, Ioannis; Fournel, Sandrine; Pérès, Sylvie; Woehrlé, Frédérique

    2008-05-31

    This phase II, randomized, open-label field trial was designed to evaluate and compare the safety and efficacy of four treatment durations (10, 20, 28 or 40 days) with marbofloxacin administered orally at the dosage of 2mg/kg once a day for canine visceral leishmaniosis. Twenty-four dogs naturally infected with visceral leishmaniosis and without biochemical disorder evidences of renal insufficiency, were recruited by two Greek veterinarian clinics. They were also randomly assigned to one of the four treatment duration groups, and have been clinically, haematologically, biochemically and parasitologically followed-up regularly for 9 months. Efficacy was achieved for 5/6 dogs treated for 28 days, 4/6 dogs treated for 10 or 20 days and for 3/6 dogs treated for 40 days. Moreover, efficacy was reached more quickly (58.4 days) in dogs treated for 28 days. Improvement of clinical signs tended to be better and faster in the 28 days treatment group too. After 9 months of follow-up, a total of three cases could be considered as relapsing (two dogs treated for 40 days and one dog treated for 28 days). There was a significant reduction in amastigotes density in macrophages after 3 months in the four groups when compared with the parasite density at inclusion. No adverse effects were noticed during this 9 months study. Results obtained with marbofloxacin at the dosage of 2mg/kg once a day for 28 days seem encouraging and may offer a safe alternative for treating canine visceral leishmaniosis.

  18. Safety and efficacy of repeat thrombolytic treatment after acute myocardial infarction.

    PubMed Central

    White, H D; Cross, D B; Williams, B F; Norris, R M

    1990-01-01

    Thrombolytic treatment for acute myocardial infarction increases the risk of subsequent reocclusion of the infarct related artery. The efficacy and safety of repeat thrombolytic treatment was assessed in 31 patients treated with streptokinase (n = 13) or tissue plasminogen activator (n = 18) a median of five days (1-716) after the first infusion. The indication for readministration was prolonged chest pain with new ST segment elevation. Efficacy was assessed by infarct artery patency at angiography at a median of eight days after readministration in 22 patients and by non-invasive criteria in 23 patients (reperfusion was deemed to be likely if serum creatine kinase was not increased or reached a peak less than 12 hours after infarction). Angiography showed patency of 70% of the infarct arteries after readministration of streptokinase and of 75% after tissue plasminogen activator. The corresponding patency rates assessed noninvasively were 73% and 75%. Reinfarction was prevented in nine (29%) patients. Allergic reactions occurred in four of eight patients who received streptokinase twice (plasmacytosis and acute reversible renal failure developed in one patient). Two patients had major bleeding and two minor bleeding, all after tissue plasminogen activator, and one of them died of cerebral haemorrhage. Repeat thrombolytic treatment results in late patency rates similar to the rates after the initial administration. Allergic reactions were common in those treated twice with streptokinase. PMID:2119665

  19. Efficacy of fenbendazole and levamisole treatments in captive Houston toads (Bufo [Anaxyrus] houstonensis).

    PubMed

    Bianchi, Catherine M; Johnson, Cassidy B; Howard, Lauren L; Crump, Paul

    2014-09-01

    Effective disease monitoring and prevention is critical to the success of captive amphibian care. Nematodes, including the genera Rhabdias and Strongyloides, are known to contribute to mortality in captive amphibians and have been identified in the Houston Zoo's endangered Houston toad (Bufo [Anaxyrus] houstonensis) captive assurance colony. Five years of fecal data for the toad colony were compiled and analyzed in order to investigate the efficacy of two anthelminthic medications, fenbendazole (FBZ) and levamisole (LMS), which were used to control nematode infections. Both FBZ (dusted onto food items) and topical LMS (6.5 to 13.5 mg/kg) significantly reduced the number of nematode eggs, larvae, and adults observed by fecal parasitologic examination. There were no significant differences between treatments, and egg reappearance periods were difficult to compare as a result of low sample size. No adverse effects from either anthelminthic treatment were observed. Both topical LMS and oral FBZ appear to be safe and efficacious treatments for the reduction of the internal nematode burden in captive Houston toads.

  20. A Comprehensive Comparison of the Efficacy and Tolerability of Racecadotril with Other Treatments of Acute Diarrhea in Adults

    PubMed Central

    Fischbach, Wolfgang; Andresen, Viola; Eberlin, Marion; Mueck, Tobias; Layer, Peter

    2016-01-01

    Racecadotril is a guideline-recommended treatment to alleviate symptoms of acute diarrhea. A systematic review of randomized studies was performed comparing efficacy and safety of treatment with racecadotril to that with placebo or active treatments in adults. In five double-blind studies, racecadotril and placebo had comparable tolerability, but racecadotril was more effective. This was consistent across multiple efficacy parameters including duration of diarrhea, number of diarrheic stools, abdominal pain, and meteorism; it was also consistent across countries in Africa, Asia, and Europe. In six randomized studies in outpatients comparing racecadotril to loperamide, resolution of symptoms occurred with similar speed and efficacy; however, racecadotril treatment was associated with less rebound constipation and less abdominal discomfort. The seventh comparative study performed in geriatric nursing home residents reported a superior efficacy of racecadotril. In direct comparison with Saccharomyces boulardii treatment, racecadotril exhibited similar tolerability but was more efficacious. One study compared racecadotril to octreotide in patients with acute diarrhea requiring hospitalization, rehydration, and antibiotic treatment; in this cohort, octreotide was more efficacious than racecadotril. In conclusion, in adults with acute diarrhea, racecadotril is more efficacious than placebo or S. boulardii, similarly efficacious as loperamide and, in patients with moderate to severe disease as add-on to antibiotics, less than octreotide. The tolerability of racecadotril is similar to that of placebo or S. boulardii and better than that of loperamide, particularly with regard to risk of rebound constipation. Taken together, these data demonstrate that racecadotril is a suitable treatment to alleviate symptoms of acute diarrhea in adults. PMID:27790616

  1. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    PubMed Central

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  2. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy.

    PubMed

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; Dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a "safer" approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments.

  3. Doxazosin: safety and efficacy in the treatment of resistant arterial hypertension.

    PubMed

    Ceral, Jiri; Solar, Miroslav

    2009-01-01

    Five classes of antihypertensive drugs have proven efficacy in the prevention of cardiovascular morbidity and mortality. Among the remaining antihypertensives, the action of alpha-1-blockers is supported by most clinical evidence; however, in combination therapy, the published data concern their use as third-line drugs at the most. The data from patients with drug-resistant hypertension remain limited. The aim of our study was to evaluate the efficacy and safety of doxazosin in this clinical setting. Data from 97 patients with resistant hypertension treated by doxazosin were analysed retrospectively. Doxazosin was usually added as the fifth antihypertensive drug in individuals who were either unresponsive to or intolerant of the combination of other antihypertensives. The dose of doxazosin ranged from 2 to 16 mg/day. The mean duration of follow-up was 21+/-17 months. Adverse events related to doxazosin treatment were rare and led to discontinuation of the therapy in only five patients (5.2%). Data from 34 patients were subjected to analysis of efficacy. In this subgroup, doxazosin therapy led to the reduction of blood pressure from 159+/-20/92+/-14 to 126+/-16/73+/-10 mmHg. We found that doxazosin is a well-tolerated and effective drug for patients with resistant arterial hypertension who require a combination of multiple antihypertensive drugs.

  4. The Efficacy of Acupuncture for the Treatment of Sciatica: A Systematic Review and Meta-Analysis

    PubMed Central

    Ji, Mei; Wang, Xiaoxia; Chen, Meijuan; Shen, Yan; Zhang, Xu; Yang, Jin

    2015-01-01

    Background. Sciatica is one of the most frequently reported complaints; it affects quality of life and reduces social and economic efficacy. Clinical studies on the efficacy of acupuncture therapy in sciatica are increasing, while systematic reviews assessing the efficacy of acupuncture therapy are still lacking. Objective. This study aims to assess the effectiveness of acupuncture therapy for sciatica. Methods. Comprehensive searches of 8 databases were conducted up until April 2015. Outcomes included effectiveness (proportion of patients who improved totally or partly in clinical symptoms), pain intensity, and pain threshold. Effect sizes were presented as risk ratio (RR) and mean difference (MD). Pooled effect sizes were calculated by fixed effects or random effects model. Results. A total of 12 studies (involving 1842 participants) were included. Results showed that acupuncture was more effective than conventional Western medicine (CWM) in outcomes effectiveness (RR 1.21, 95% CI: 1.16–1.25), pain intensity (MD −1.25, 95% CI: −1.63 to −0.86), and pain threshold (MD: 1.08, 95% CI: 0.98–1.17). Subgroup and sensitivity analysis found that the results did not change in different treatment method and drug categories substantially. The reported adverse effects were acceptable. Conclusions. Acupuncture may be effective in treating the pain associated with sciatica. PMID:26425130

  5. Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine*

    PubMed

    Lôo, H.; Saiz-Ruiz, J.; Costa E Silva, J. A.; Ansseau, M.; Herrington, R.; Vaz-Serra, A.; Dilling, H.; De Risio, S.

    2001-01-01

    Depression is treated by a great variety of antidepressant treatments. SSRIs (such as fluoxetine) are well known: it is, however, sure that further progress is needed and the search for antidepressants with other mechanisms of action (such as tianeptine) or different efficacy is still of interest. A multinational study compared tianeptine with fluoxetine in 387 patients with Depressive Episode, or Recurrent Depressive Disorder, or Bipolar Affective Disorder (ICD-10), in a double-blind parallel group design. They were treated for six weeks. At inclusion, no significant difference between groups was shown. Final MADRS scores were 15.7 and 15.8 with tianeptine and fluoxetine, respectively (ITT population) (p = 0.944). MADRS responders were 58% and 56% with tianeptine and fluoxetine, respectively (p = 0.710). No statistical difference was observed for the other efficacy parameters. Thirty-six withdrawals occurred in each group, without any difference for the reasons of discontinuation. There was no major difference between groups for the other safety parameters. In this study, both tianeptine and fluoxetine exhibited a good efficacy and safety. Copyright 1999 Elsevier Science B. V. All rights reserved.

  6. Efficacy versus systemic effects of six topical steroids in the treatment of atopic dermatitis of childhood.

    PubMed

    Queille, C; Pommarede, R; Saurat, J H

    1984-01-01

    Six groups of children suffering from widespread atopic dermatitis were treated once daily with six topical steroids of different potency. Systemic effects were measured by the morning estimation of plasma cortisol. A clear relationship was demonstrated between clinical efficacy of the steroid treatment and degree of reduced adrenal function. This study demonstrated that a rapid and marked therapeutic effect can be obtained with potent topical steroids applied once daily without occlusion, but in children is accompanied by a fall in plasma cortisol. PMID:6494068

  7. Complex regional pain syndrome type 1. Some treatments assessed versus placebo, limited efficacy.

    PubMed

    2009-12-01

    (1) Complex regional pain syndrome type 1 generally occurs after trauma and usually affects a limb; (2) How is complex regional pain syndrome type 1 diagnosed? What is its natural course? How safe and effective are available treatments? To answer these questions, we reviewed the literature using the standard Prescrire methodology; (3) Diagnosis is mainly based on clinical features, including pain disproportionate to the initial trauma, associated with cutaneous vasomotor, trophic and sweating disorders; (4) Some clinical signs call for additional examinations to help rule out another vascular, neurological, infectious or rheumatic disorder. Radiological evidence of bone demineralisation supports the diagnosis, but radiography, magnetic resonance imaging (MRI) and scintigraphy generally contribute little to the diagnosis of complex regional pain syndrome; (5) Some patients recover spontaneously after a few weeks, while others develop chronic pain or even severe disability after a period of years; (6) The results of small placebo-controlled trials suggest that corticosteroids are effective during the initial phase of this syndrome; (7) A very high oral dose of alendronic acid provided sustained pain relief in a randomised trial. Other studies suggest that bisphosphonates have some impact. The adverse effects of alendronic acid given at such high doses are poorly known; (8) Calcitonin, antiepileptics, antidepressants and opiates have no proven efficacy; (9) Transcutaneous neurostimulation is rapidly effective and safe, but its efficacy also diminishes rapidly. Therefore, the sessions have to take place at increasingly shorter intervals. (10) Spinal neurostimulation with implanted electrodes has been assessed in a comparative trial in 54 patients. Some efficacy was observed, but one-third of patients had complications requiring further surgery; (11) Various substances have been given intravenously with the goal of achieving regional anaesthesia, but none was found to

  8. Evidence for efficacy of acute treatment of episodic tension-type headache: methodological critique of randomised trials for oral treatments.

    PubMed

    Moore, R Andrew; Derry, Sheena; Wiffen, Philip J; Straube, Sebastian; Bendtsen, Lars

    2014-11-01

    The International Headache Society (IHS) provides guidance on the conduct of trials for acute treatment of episodic tension-type headache (TTH), a common disorder with considerable disability. Electronic and other searches identified randomised, double-blind trials of oral drugs treating episodic TTH with moderate or severe pain at baseline, or that tested drugs at first pain onset. The aims were to review methods, quality, and outcomes reported (in particular the IHS-recommended primary efficacy parameter pain-free after 2 hours), and to assess efficacy by meta-analysis. We identified 58 reports: 55 from previous reviews and searches, 2 unpublished reports, and 1 clinical trial report with results. We included 40 reports of 55 randomised trials involving 12,143 patients. Reporting quality was generally good, with potential risk of bias from incomplete outcome reporting and small size; the 23 largest trials involved 82% of patients. Few trials reported IHS outcomes. The number needed to treat values for being pain-free at 2 hours compared with placebo were 8.7 (95% confidence interval [CI] 6.2 to 15) for paracetamol 1000 mg, 8.9 (95% CI 5.9 to 18) for ibuprofen 400mg, and 9.8 (95% CI 5.1 to 146) for ketoprofen 25mg. Lower (better) number needed to treat values were calculated for outcomes of mild or no pain at 2 hours, and patient global assessment. These were similar to values for these drugs in migraine. No other drugs had evaluable results for these patient-centred outcomes. There was no evidence that any one outcome was better than others. The evidence available for treatment efficacy is small in comparison to the size of the clinical problem.

  9. Tolerability and Efficacy of Retinoic Acid Given after Full-face Peel Treatment of Photodamaged Skin

    PubMed Central

    Hu, Judy Y.; Biron, Julie A.; Yatskayer, Margarita; Dahl, Amanda; Oresajo, Christian

    2011-01-01

    Objective: All-trans retinoic acid is a well-established topical treatment of photodamaged skin. This study assessed the tolerance and efficacy of all-trans retinoic acid after full-face treatment with a chemical peel. Design: This was a split-face, randomized study. One side of each face was treated with peel and the other side with peel and all-trans retinoic acid (3%). Four treatments were given during the 10-week study period. Setting: Physician office. Participants: Fifteen female subjects 39 to 55 years of age. Measurements: Results were evaluated at Baseline; Weeks 4, 7, and 10; and at a 13-week follow-up visit by dermal grading of visual symptoms of irritation, subjective experiences of irritation, clinical grading of skin condition, and self-assessment questionnaires. Results: Both peel and peel plus all-trans retinoic acid treatments achieved significant improvement in fine lines, radiance, roughness, skin tone clarity, skin tone evenness, and hyperpigmentation appearance. Improvement in wrinkles and firmness was not observed in the peel plus all-trans retinoic acid arm, while pore appearance failed to improve in either treatment arm. Improvement in overall facial appearance was greater in the peel alone arm. Peel alone and the addition of all-trans retinoic acid did not cause dryness, edema, or peeling, and the frequency of peel-induced erythema did not increase with the addition of all-trans retinoic acid. Subject-perceived improvements with the peel treatment did not differ significantly from subject-perceived improvements of the peel plus all-trans retinoic acid treatment. Adverse events requiring intervention or discontinuing treatment were not observed in either treatment arm. Conclusion: The addition of all-trans retinoic acid after peel treatment does not significantly enhance peel-induced improvement in photoaging parameters, peel-induced adverse effects, and subject-perceived improvements. PMID:22010055

  10. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

    PubMed Central

    Qin, Liang; Xu, Tianyuan; Xia, Leilei; Wang, Xianjin; Zhang, Xiang; Zhang, Xiaohua; Zhu, Zhaowei; Zhong, Shan; Wang, Chuandong; Shen, Zhoujun

    2016-01-01

    Background It has been demonstrated that chloroquine (CQ) enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP) in the treatment of adrenocortical carcinoma (ACC). In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo. Methods The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62) and apoptosis relative protein (Bax and Bcl-2) levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy. Results The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05). In vitro concomitant therapy (DDP and CQ) was more effective in restraining SW13 cell proliferation. DDP could promote cell apoptosis and induce autophagy in SW13 cells. Concomitant therapy further promoted cell apoptosis by inhibiting autophagy. In vivo, we found that concomitant therapy was more potent than DDP monotherapy in inhibiting the growth of xenografted tumors and prolonging the survival of tumor-bearing mice. Conclusion The antitumor ability of DDP was related to autophagy activity, and the concomitant therapy (DDP and CQ) could be an

  11. Evaluating the efficacy of therapeutic HIV vaccines through analytical treatment interruptions

    PubMed Central

    Graziani, Gina M; Angel, Jonathan B

    2015-01-01

    Introduction The development of an effective therapeutic HIV vaccine that induces immunologic control of viral replication, thereby eliminating or reducing the need for antiretroviral therapy (ART), would be of great value. Besides the obvious challenges of developing a therapeutic vaccine that would generate effective, sustained anti-HIV immunity in infected individuals is the issue of how to best assess the efficacy of vaccine candidates. Discussion This review discusses the various outcome measures assessed in therapeutic HIV vaccine clinical trials involving individuals receiving suppressive ART, with a particular focus on the role of analytical treatment interruption (ATI) as a way to assess the virologic control induced by an immunotherapy. This strategy is critical given that there are otherwise no readily available measures to determine the ability of a vaccine-induced immune response to effectively control HIV replication. The various outcome measures that have been used to assess vaccine efficacy in published therapeutic HIV vaccine clinical trials will also be discussed. Outcome measures have included the kinetics of viral rebound, the new viral set point and changes in the size of the viral reservoir. Clinically relevant outcomes such as the CD4 decline, the time to resume therapy or the time to meet the criterion to resume therapy, the proportion of participants who resume therapy and/or the development of clinical symptoms such as acute retroviral syndrome are also measures of vaccine efficacy. Conclusions Given the lack of consistency between therapeutic HIV vaccine trials in how efficacy is assessed, comparing vaccines has been difficult. It would, therefore, be beneficial to determine the most clinically relevant measure for use in future studies. Other recommendations for future clinical trials also include studying compartments in addition to blood and replacing ATIs with single-copy assays in situations in which the use of an ATI is not ideal

  12. Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors

    SciTech Connect

    Siemann, Dietmar W. . E-mail: siemadw@ufl.edu; Shi Wenyin

    2004-11-15

    Purpose: To evaluate the antitumor efficacy of a vascular targeting strategy that combines an agent that disrupts established tumor blood vessels (ZD6126) with one that interferes with new vessel formation (ZD6474) in models of human renal cell carcinoma (Caki-1) and Kaposi's sarcoma (KSY-1). Methods and materials: Caki-1 and KSY-1 xenograft-bearing nude mice were treated with ZD6126 and ZD6474 either as single agents or in combination when the tumors reached a size of {approx}200 mm{sup 3}. ZD6126 therapy consisted of three doses of 100 mg/kg administered 1, 3, and 5 days after the tumor reached the starting size. ZD6474 was administered daily (25 mg/kg) on Days 1-5. In the combination studies, ZD6474 treatment began immediately after the first dose of ZD6126. The tumor response to treatment was evaluated using a regrowth delay endpoint. Results: Significant tumor growth delays were observed in both tumor models with either agent with the treatment regimen used. In the Caki-1 and KSY-1 models, respectively, ZD6126 treatment resulted in a tumor growth delay of 23 and 26 days and ZD6474 produced a tumor growth delay of 24.5 and 14.5 days. When ZD6126 and ZD6474 were combined, the tumor growth delays increased to 55 (Caki-1) and 86 (KSY-1) days. In the KSY-1 model, the combination therapy also resulted in 3 of 8 long-term tumor-free survivors. Conclusion: These results indicate that statistically significant antitumor efficacy can be achieved using a treatment strategy that combines a therapy that targets the established tumor blood vessels with one that interferes with the process of angiogenesis.

  13. Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis.

    PubMed

    Inderjeeth, Charles A; Glendenning, Paul; Ratnagobal, Shoba; Inderjeeth, Diren Che; Ondhia, Chandni

    2015-01-01

    Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration. A literature search using "ibandronate", "postmenopausal osteoporosis", "fracture", and "bone mineral density" (BMD) revealed 168 publications. The Phase III BONE study, using low dose 2.5 mg daily oral ibandronate demonstrated 49% relative risk reduction (RRR) in clinical vertebral fracture after 3 years. Non-vertebral fracture (NVF) reduction was demonstrated in a subgroup (pretreatment T-score ≤ -3.0; RRR 69%) and a meta-analysis of high annual doses (150 mg oral monthly or intravenous equivalent of ibandronate; RRR 38%). Hip fracture reduction was not demonstrated. Long-term treatment efficacy has been confirmed over 5 years. Long term safety is comparable to placebo over 3 years apart from flu-like symptoms which are more common with oral monthly and intravenous treatments. No cases of atypical femoral fracture or osteonecrosis of the jaw have been reported in randomized controlled trial studies. Ibandronate inhibits FPPS more than alendronate but less than other BPs which could explain rate of action onset. Ibandronate has a higher affinity for hydroxyapatite compared with risedronate but less than other BPs which could affect skeletal distribution and rate of action offset. High doses (150 mg oral monthly or intravenous equivalent) were superior to low doses (oral 2.5 mg daily) according to 1 year BMD change. Data are limited by patient selection, statistical power, under-dosing, and absence of placebo groups in high dose studies. Ibandronate treatment offers different doses and modalities of administration which could translate into higher adherence rates, an important factor when the two main limitations of BP treatment are initiation and adherence rates

  14. Mechanistic perspectives on cancer chemoprevention/chemotherapeutic effects of thymoquinone.

    PubMed

    Kundu, Juthika; Chun, Kyung-Soo; Aruoma, Okezie I; Kundu, Joydeb Kumar

    2014-10-01

    The bioactive natural products (plant secondary metabolites) are widely known to possess therapeutic value for the prevention and treatment of various chronic diseases including cancer. Thymoquinone (2-methyl-5-isopropyl-1,4-benzoquinone; TQ), a monoterpene present in black cumin seeds, exhibits pleiotropic pharmacological activities including antioxidant, anti-inflammatory, antidiabetic and antitumor effects. TQ inhibits experimental carcinogenesis in a wide range of animal models and has been shown to arrest the growth of various cancer cells in culture as well as xenograft tumors in vivo. The mechanistic basis of anticancer effects of TQ includes the inhibition of carcinogen metabolizing enzyme activity and oxidative damage of cellular macromolecules, attenuation of inflammation, induction of cell cycle arrest and apoptosis in tumor cells, blockade of tumor angiogenesis, and suppression of migration, invasion and metastasis of cancer cells. TQ shows synergistic and/or potentiating anticancer effects when combined with clinically used chemotherapeutic agents. At the molecular level, TQ targets various components of intracellular signaling pathways, particularly a variety of upstream kinases and transcription factors, which are aberrantly activated during the course of tumorigenesis. PMID:25847385

  15. Efficacy of Physical Therapy in the Treatment of Gonarthrosis in Physically Burdened Working Men

    PubMed Central

    Kasumovic, Mersija; Gorcevic, Emir; Gorcevic, Semir; Osmanovic, Jasna

    2013-01-01

    Introduction: Gonarthrosis is most frequently defined as the change involving damage of the articular cartilage of the knee joint, emergence of abnormal knee tissue, reactive changes in synovial membrane, and pathological synovial fluid. The site of initial damage most often remains unknown. Goal of the research The goal: The goal of this research is to demonstrate the efficacy of individual physical therapy during the medical treatment for gonarthrosis in the working population engaged in physical labour, and to compare the state of pain and mobility before and after the treatment. Subjects and research methods: The research encompassed 30 subjects diagnosed with gonarthrosis, and it was conducted in the Institute of Occupational Health and Sports Medicine of the Zenica-Doboj Canton. On the basis of the applied physical treatments, we divided the subjects into control group and treatment group. All the subjects were treated during 21 days. Results and conclusions: In the largest number of subjects in both groups gonarthrosis occurred primarily as a consequence of knee joint trauma, and then because of weight and physical strain. Of the total number of subjects covered by this research, 9 subjects in control and 8 in treatment group had gonarthrosis of their right knee. 4 subjects in the control and 5 in the treatment group had gonarthrosis of the left knee, while 2 subjects from each group had gonarthrosis on both knees. By the analysis of clinical symptoms of gonarthrosis prior to the treatment, it was found that all the subjects from both groups had pain symptom, in 13 subjects from the control and 14 subjects from the treatment group limited range of motion was established, while 8 subjects from control and 9 subjects from treatment group had swelling in the joint area. The condition of the subjects prior to the treatment was analyzed by means of pain scale, and it was found that both groups experienced moderate level of pain before the treatment. After the 21

  16. The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome.

    PubMed

    Montouris, Georgia D; Wheless, James W; Glauser, Tracy A

    2014-09-01

    Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that appears in childhood. LGS is characterized by a slow spike-wave pattern on electroencephalogram (EEG), cognitive impairment, and multiple seizure types. This mixture of seizure types, along with the need to use more than one type of medication, makes LGS one of the most complicated epilepsies to treat successfully. Recent developments in approved therapies for the treatment of LGS offer physicians more options, but also make developing a treatment strategy that minimizes adverse events more challenging. There are currently 5 treatment options for LGS: felbamate, lamotrigine, topiramate, rufinamide, and clobazam, and several others that are used off-label, each of which has benefits and limitations. There are several factors that must be considered when determining which medication to use when treating patients with LGS, including efficacy, which is assessed by seizure frequency, tolerability, and the anticipated duration of treatment. In this article, data supporting current treatment options are discussed, and important considerations about the treatment of LGS are reviewed. PMID:25284033

  17. Comparison of the efficacies of patching and penalization therapies for the treatment of amblyopia patients

    PubMed Central

    Cabi, Cemalettin; Sayman Muslubas, Isil Bahar; Aydin Oral, Ayse Yesim; Dastan, Metin

    2014-01-01

    AIM To compare the efficacies of patching and penalization therapies for the treatment of amblyopia patients. METHODS The records of 64 eyes of 50 patients 7 to 16y of age who had presented to our clinics with a diagnosis of amblyopia, were evaluated retrospectively. Forty eyes of 26 patients who had received patching therapy and 24 eyes of 24 patients who had received penalization therapy included in this study. The latencies and amplitudes of visual evoked potential (VEP) records and best corrected visual acuities (BCVA) of these two groups were compared before and six months after the treatment. RESULTS In both patching and the penalization groups, the visual acuities increased significantly following the treatments (P<0.05). The latency measurements of the P100 wave obtained at 1.0°, 15 arc min. Patterns of both groups significantly decreased following the 6-months-treatment. However, the amplitude measurements increased (P<0.05). CONCLUSION The patching and the penalization methods, which are the main methods used in the treatment of amblyopia, were also effective over the age of 7y, which has been accepted as the critical age for the treatment of amblyopia. PMID:24967195

  18. The efficacy and tolerability of pharmacologic treatment options for Lennox-Gastaut syndrome.

    PubMed

    Montouris, Georgia D; Wheless, James W; Glauser, Tracy A

    2014-09-01

    Lennox-Gastaut syndrome (LGS) is a severe epileptic encephalopathy that appears in childhood. LGS is characterized by a slow spike-wave pattern on electroencephalogram (EEG), cognitive impairment, and multiple seizure types. This mixture of seizure types, along with the need to use more than one type of medication, makes LGS one of the most complicated epilepsies to treat successfully. Recent developments in approved therapies for the treatment of LGS offer physicians more options, but also make developing a treatment strategy that minimizes adverse events more challenging. There are currently 5 treatment options for LGS: felbamate, lamotrigine, topiramate, rufinamide, and clobazam, and several others that are used off-label, each of which has benefits and limitations. There are several factors that must be considered when determining which medication to use when treating patients with LGS, including efficacy, which is assessed by seizure frequency, tolerability, and the anticipated duration of treatment. In this article, data supporting current treatment options are discussed, and important considerations about the treatment of LGS are reviewed.

  19. The efficacy of Behavioral Activation Treatment among Depressed Spanish-speaking Latinos

    PubMed Central

    Collado, Anahí; Calderón, Marilyn; MacPherson, Laura; Lejuez, Carl

    2016-01-01

    Objective Major depressive disorder (MDD) is highly prevalent among U.S. Spanish-speaking Latinos, but the lack of empirically-supported treatments precludes this population’s access to quality mental health care. Method Following the promising results of an open-label trial of the Behavioral Activation Treatment for Depression (BATD) among Spanish-speaking Latinos, we conducted a randomized control trial (RCT; N = 46) that compared BATD to supportive counseling. Study outcomes included depression, BATD proposed mechanisms of change, and non-specific psychotherapy factors. Results Relative to supportive counseling, BATD led to greater decreases in depressive symptoms over time (p = 0.04) and greater MDD remission at the end of treatment (p = 0.01). Activity level (p = 0.01) and environmental reward (p = 0.05) showed greater increases over time among those who received BATD compared to supportive counseling. Treatment adherence, therapeutic alliance, and treatment satisfaction did not differ between the groups over time (ps > 0.17). The one-month follow-up suggested sustained clinical gains across therapies. Conclusions The current study adds to a growing treatment literature and provides support that BATD is efficacious in reducing depression and increasing activity level and environmental reward in the largest, yet historically underserved U.S. ethnic minority population. This trial sets the stage for a larger RCT that evaluates the transportability and generalizability of BATD in an effectiveness trial. PMID:27054826

  20. The efficacy of recommended treatments for veterans with PTSD: A metaregression analysis.

    PubMed

    Haagen, Joris F G; Smid, Geert E; Knipscheer, Jeroen W; Kleber, Rolf J

    2015-08-01

    Soldiers and veterans diagnosed with PTSD benefit less from psychotherapy than non-military populations. The current meta-analysis identified treatment predictors for traumatised soldiers and veterans, using data from studies examining guideline recommended interventions, namely: EMDR, exposure, cognitive, cognitive restructuring, cognitive processing, trauma-focused cognitive behavioural, and stress management therapies. A systematic search identified 57 eligible studies reporting on 69 treated samples. Exposure therapy and cognitive processing therapy were more effective than EMDR and stress management therapy. Group-only therapy formats performed worse compared with individual-only formats, or a combination of both formats. After controlling for study design variables, EMDR no longer negatively predicted treatment outcome. The number of trauma-focused sessions, unlike the total number of psychotherapy sessions, positively predicted treatment outcome. We found a relationship between PTSD pretreatment severity levels and treatment outcome, indicating lower treatment gains at low and high PTSD severity levels compared with moderate severity levels. Demographic variables did not influence treatment outcome. Consequently, soldiers and veterans are best served using exposure interventions to target PTSD. Our results did not support a group-only therapy format. Recommended interventions appear less effective at relatively low and high patient PTSD severity levels. Future high-quality studies are needed to determine the efficacy of EMDR.

  1. Treatment Efficacy for Non-Cardiovascular Chest Pain: A Systematic Review and Meta-Analysis

    PubMed Central

    Burgstaller, Jakob M.; Jenni, Boris F.; Steurer, Johann; Held, Ulrike; Wertli, Maria M.

    2014-01-01

    Background Non-cardiovascular chest pain (NCCP) leads to impaired quality of life and is associated with a high disease burden. Upon ruling out cardiovascular disease, only vague recommendations exist for further treatment. Objectives To summarize treatment efficacy for patients presenting with NCCP. Methods Systematic review and meta-analysis. In July 2013, Medline, Web of Knowledge, Embase, EBSCOhost, Cochrane Reviews and Trials, and Scopus were searched. Hand and bibliography searches were also conducted. Randomized controlled trials (RCTs) evaluating non-surgical treatments in patients with NCCP were included. Exclusion criteria were poor study quality and small sample size (<10 patients per group). Results Thirty eligible RCT’s were included. Most studies assessed PPI efficacy for gastroesophageal reflux disorders (GERD, n = 10). Two RCTs included musculoskeletal chest pain, seven psychotropic drugs, and eleven various psychological interventions. Study quality was high in five RCTs and acceptable in 25. PPI treatment in patients with GERD (5 RCTs, 192 patients) was more effective than placebo [pooled OR 11.7 (95% CI 5.5 to 25.0, heterogeneity I2 = 6.1%)]. The pooled OR in GERD negative patients (4 RCTs, 156 patients) was 0.8 (95% CI 0.2 to 2.8, heterogeneity I2 = 50.4%). In musculoskeletal NCCP (2 RCTs, 229 patients) manual therapy was more effective than usual care but not than home exercise [pooled mean difference 0.5 (95% CI −0.3 to 1.3, heterogeneity I2 = 46.2%)]. The findings for cognitive behavioral treatment, serotonin reuptake inhibitors, tricyclic antidepressants were mixed. Most evidence was available for cognitive behavioral treatment interventions. Limitations Only a small number of studies were available. Conclusions Timely diagnostic evaluation and treatment of the disease underlying NCCP is important. For patients with suspected GERD, high-dose treatment with PPI is effective. Only limited evidence was available for most

  2. Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

    PubMed Central

    Wang, Yunfeng; Yu, Ting; Wang, Yun; Jiang, Liuqin; Lin, Lin

    2015-01-01

    Aim The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome. Methods We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis. Results Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups. Conclusions TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS. PMID:26252008

  3. Willpower versus “Skillpower:” Examining How Self-Efficacy Works in Treatment for Marijuana Dependence

    PubMed Central

    Litt, Mark D.; Kadden, Ronald M.

    2015-01-01

    Self-efficacy has repeatedly been demonstrated to be a robust predictor of outcomes in the treatment of marijuana use disorders. It is not clear, however, how increases in confidence in ability to refrain from use get translated into actual improvements in drug-related outcomes. Marlatt, among others, viewed the acquisition and use of coping skills as the key to behavior change, and self-efficacy as a cognitive state that enabled coping. But that model of behavior change has not been supported, and few studies have shown that the effects of self-efficacy are mediated by coping or by other processes. The current study combined three marijuana treatment trials comprising 901 patients to examine the relationships between self-efficacy, coping, and potential mediators, to determine if the effects of self-efficacy on outcomes could be explained. Results of multilevel models indicated that self-efficacy was a strong predictor of adaptive outcomes in all trials, even when no active treatment was provided. Tests of mediation showed that effects of self-efficacy on marijuana use and on marijuana-related problems were partially mediated by use of coping skills and by reductions in emotional distress, but that direct effects of self-efficacy remained largely unexplained. The results are seen as supportive of efforts to improve coping skills and reduce distress in marijuana treatment, but also suggest that additional research is required to discover what is actually occurring when substance use changes, and how self-efficacy enables those changes. PMID:25938628

  4. Efficacy of Retigabine in Adjunctive Treatment of Partial Onset Seizures in Adults

    PubMed Central

    Splinter, Michele Y.

    2013-01-01

    Objective To evaluate efficacy and tolerability of retigabine (ezogabine, US adopted name) in the adjunctive treatment of partial-onset seizures in adults. Retigabine is the first anticonvulsant in its class, decreasing neuronal excitability by opening voltage-gated potassium channels. Methods MEDLINE and EMBASE were systematically searched using search terms retigabine and ezogabine for randomized controlled trials published from 1980 through August 17, 2013. Additionally, articles relating to pharmacology, pharmacokinetics, tolerability and interactions were examined for inclusion. Published abstracts and websites of the Food and Drug Administration and European Medication Agency were reviewed for additional relevant information. Results One phase IIb and two phase III trials were identified. Retigabine has been reported to have dose dependent efficacy in adjunctive treatment of resistant partial-onset seizures in adults in doses of 600, 900 and 1200 mg/day. Similar to other anticonvulsants, the most common adverse events were central nervous system related. Retigabine has several unique adverse events compared to other anticonvulsants: urinary retention and, with extended use, pigment changes to the skin and retina. Retigabine is metabolized by glucuronidation and acetylation. There are few drug interactions with retigabine. Conclusions Retigabine has been shown to have efficacy when used as adjunctive therapy in partial-onset seizures. It has a novel mechanism of action, activation of voltage-gated potassium channels. It has less drug interactions than many other anticonvulsants because it is not metabolized through the P-450 system. Its place in therapy has yet to be determined, especially with recent reports of pigment discoloration of skin and the retina with extended use. PMID:24250245

  5. Efficacy and Safety of Grapefruit Juice Intake Accompanying Tacrolimus Treatment in Connective Tissue Disease Patients.

    PubMed

    Tsuji, Hideaki; Ohmura, Koichiro; Nakashima, Ran; Hashimoto, Motomu; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Fujii, Takao; Mimori, Tsuneyo

    2016-01-01

    Objective It is well known that grapefruit juice (GFJ) elevates the blood tacrolimus (TAC) concentration. We investigated the efficacy and safety of GFJ intake with TAC in cases of connective tissue diseases in which the TAC blood concentration was insufficiently high for clinical improvement, even when 3 mg/day or more of TAC was administered. Methods Seven patients took 200 mL of GFJ every day. The trough levels of the TAC blood concentration were measured before and after GFJ intake and the clinical courses were monitored thereafter. Results First, we surveyed the blood TAC trough levels of 30 recent patients who took 3 mg/day of TAC, and found that 21 patients (70%) did not achieve the minimum target TAC concentration (>5 ng/mL). Seven patients took GFJ due to a lack of efficacy and a relatively low TAC blood concentration. GFJ increased the TAC level from 4.3±2.4 ng/mL to 13.8±6.9 ng/mL (average increase: 3.3-fold). GFJ was also effective in achieving a clinical improvement in most cases without causing any severe adverse events, and it helped to decrease the dosages of glucocorticoid and TAC. In some cases, the blood TAC concentration fluctuated for no apparent reason. Conclusion GFJ intake was effective for the elevation of TAC concentration by approximately three fold and clinical improvement, but special care is required for monitoring its influence on concomitantly used drugs as well as TAC concentration. The addition of GFJ to TAC treatment could be an efficacious treatment option, when the plasma TAC concentration does not reach the minimal target concentration. PMID:27301503

  6. Efficacy and safety findings from naturalistic fluoxetine drug treatment in adolescent and young adult patients.

    PubMed

    Dittmann, R W; Czekalla, J; Hundemer, H P; Linden, M

    2000-01-01

    This article reports on the efficacy and safety of the selective serotonin reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data were derived from naturalistic drug utilization observation (DUO) studies with fluoxetine (n = 18,759 patients). Data collection--at the start and the end of the observation period (< or =6 weeks)--included patient characteristics, diagnoses, medication, co-medication, efficacy, and adverse events (AEs). Nonparametric statistics and descriptive p values (two-tailed) were used. Analyses revealed various differences between PN (n = 56) and GPI (n = 157) samples as to patient and treatment characteristics (p < 0.001-0.08). Based on both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements in their symptomatology over time, including suicidality (all p < 0.001; there were no group differences). Overall AE rates were higher in PN patients (p < 0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were typical for fluoxetine and the total DUO samples. In fact, AE rates were lower compared to controlled trials. Findings suggest that PN patients were more severely ill at observation start and suffered a more complicated treatment course. However, clinical efficacy showed highly significant improvements in both subgroups; AE rates were low in both--although higher in PN patients. Thus, results support a positive benefit/risk ratio of fluoxetine use for this young patient population.

  7. Efficacy of Elaeagnus Angustifolia extract in the treatment of knee osteoarthritis: a randomized controlled trial

    PubMed Central

    Panahi, Yunes; Alishiri, Gholam Hossein; Bayat, Noushin; Hosseini, Seyed Morteza; Sahebkar, Amirhossein

    2016-01-01

    Osteoarthritis (OA) is one of the most common musculoskeletal disorders all over the world. Available anti-arthritic medications have only partial efficacy and their long-term use is associated with adverse events. Elaeagnus Angustifolia (EA) is a medicinal plant with analgesic and anti-inflammatory properties. The present study evaluated the impact of two doses of EA extract compared with ibuprofen on the severity of disease in patients with knee OA. This study was designed as a randomized, double blind, active-controlled and parallel group trial. Patients with OA were randomized to receive 300 mg/day (n=33) or 600 mg/day (n=32) of EA aqueous extract, or 800 mg/day ibuprofen (n=32) for 7 weeks. EA extract contained 0.21 % (w/w) kaempferol according to HPLC. Efficacy of treatment was assessed using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Visual Analogue Scale (VAS) of pain, Lequesne's Pain-Function Index (LPFI), and patient's global assessment (PGA) index. The amount of kaempferol in the extract was determined by HPLC method to be 0.21 % w/w. There were significant reductions in WOMAC, VAS, LPFI and PGA scores by the end of trial with all three interventions. Comparison of the changes in WOMAC, VAS and LPFI scores among the treatment groups did not reveal any significant difference between EA and ibuprofen, and between low and high doses of EA. EA was safe and well tolerated during the course of trial and no adverse event was reported. The present results suggest beneficial effects of aqueous EA extract in reducing the symptoms of OA with an efficacy comparable to that of ibuprofen. PMID:27330526

  8. EVOLVE (nebivolol evaluation for efficacy and safety in the treatment of hypertension) postmarketing surveillance study.

    PubMed

    Faruqui, Arif A

    2007-05-01

    The objective of EVOLVE [nebivolol (nevol) evaluation for efficacy and safety in the treatment of hypertension], a postmarketing surveillance (PMS) study is to identify, validate and quantify the safety and efficacy associated with the use of nebivolol. EVOLVE study was an open-label, non-comparative, prospective, one month follow-up study of 301 patients of either sex with stage 1 hypertension, as defined by the JNC VII guidelines. The data was collected from 27 centres from all over India during the period August, 2006 to December, 2006. Nebivolol (2.5-5 mg/day) was given for 1 month. Clinical assessment was done at the start of the treatment and at 15th day and 30th day follow-ups. Concomitant medications administered were also recorded. Baseline mean systolic blood pressure (SBP) was 157.73 +/- 14.16 mm Hg which dropped to 135.13 +/- 11.15 mm Hg at the end of the study. At the end of 1 month treatment the change in mean SBP was 22.6 mm Hg ie, 14.32% reduction from baseline which was statistically significant (p < 0.001). Also the baseline mean diastolic blood pressure (DBP) was 97.21 +/- 8.25 mm Hg that dropped to 83.69 +/- 6.63 mm Hg at the end of the study. At the end of one month treatment the change in mean DBP was 13.52 mmHg ie, 13.9% reduction from baseline which was significant (p < 0.001). The heart rate in this study showed a significant decrease from 86.13 +/- 9.35 at basal to 75.09 +/- 7.42 at the end of the study (p < 0.001). It was observed that at the end of one month of treatment, majority of the patients ie, 97.75% of total cases showed good to excellent response to nebivolol. EVOLVE PMS study showed that nebivolol hydrochloride is very safe and only 8.2% of cases (n = 22) reported adverse effects, the commonest being dizziness (3.28%). Less than 1% patients reported nausea, constipation, headache, weakness, tiredness and pedal oedema; 99.25% of patients reported good to excellent tolerability; 82.33% patients achieved the goals recommended by

  9. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

    PubMed Central

    Vishnu, Prakash; Aboulafia, David M

    2016-01-01

    Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP). Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim’s efficacy and safety in other primary and secondary thrombocytopenic states. PMID:27307776

  10. Efficacy of Hypnosis-Based Treatment in Amyotrophic Lateral Sclerosis: A Pilot Study

    PubMed Central

    Palmieri, Arianna; Kleinbub, Johann Roland; Calvo, Vincenzo; Sorarù, Gianni; Grasso, Irene; Messina, Irene; Sambin, Marco

    2012-01-01

    Background: Amyotrophic lateral sclerosis (ALS) and its devastating neurodegenerative consequences have an inevitably psychological impact on patients and their caregivers: however, although it would be strongly needed, there is a lack of research on the efficacy of psychological intervention. Our aim was to investigate the effect of hypnosis-based intervention on psychological and perceived physical wellbeing in patients and the indirect effect on caregivers. Methods: We recruited eight ALS volunteers patients as a pilot sample for an hypnosis intervention and self-hypnosis training protocol lasting 1 month. Anxiety and depression level was measured in patients and caregivers at pre and post treatment phase. Quality of life and perceived physical symptoms changes were also investigated in patients. Results: One month pre-post treatment improvement in depression, anxiety, and quality of life was clearly clinically observed and confirmed by psychometric analyses on questionnaire data. Moreover, decreases in physical symptoms such as pain, sleep disorders, emotional lability, and fasciculations were reported by our patients. Improvements in caregiver psychological wellbeing, likely as a consequence of patients psychological and perceived physical symptomatology improvement, were also observed. Conclusion: To the best of our knowledge, even if at a preliminary level, this is the first report on efficacy psychological intervention protocol on ALS patients. The findings provide initial support for using hypnosis and self-hypnosis training to manage some ALS physical consequences and mainly to cope its dramatic psychological implications for patients and, indirectly, for their caregivers. PMID:23162510

  11. The safety and efficacy of safinamide mesylate for the treatment of Parkinson's disease.

    PubMed

    Perez-Lloret, Santiago; Rascol, Olivier

    2016-01-01

    Safinamide (brand name Xadago®, Zambon S.p.A) is a third-generation reversible MAO-B inhibitor, which also blocks sodium voltage-sensitive channels and modulates stimulated release of glutamate. Safinamide was recently licensed by EMA for the treatment of PD as add-on therapy to a stable dose of levodopa alone or in combination with other PD medicinal products in mid-to advanced-stage fluctuating patients. It is also under review by the US FDA. Studies in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and 6OHDA-lesioned rats suggest antiparkinsonian efficacy and antidyskinesic effects. Randomized, double-blind, placebo-controlled trials have shown efficacy for the treatment of motor symptoms in stable PD patients on dopamine agonists and in fluctuating PD patients on levodopa. Significant improvement in daily ON time was also observed in the latter. This effect was maintained for at least 2 years in double-blind conditions and, interestingly, without significant worsening of dyskinesia. Clinical studies have not detected any specific safety issue other than those already known with MAO-B inhibitors. PMID:26849427

  12. Efficacy and tolerability of pharmacotherapy options for the treatment of irritability in autistic children.

    PubMed

    Kirino, Eiji

    2014-01-01

    Children with autism have a high rate of irritability and aggressive symptoms. Irritability or self-injurious behavior can result in significant harm to those affected, as well as to marked distress for their families. This paper provides a literature review regarding the efficacy and tolerability of pharmacotherapy for the treatment of irritability in autistic children. Although antipsychotics have not yet been approved for the treatment of autistic children by many countries, they are often used to reduce symptoms of behavioral problems, including irritability, aggression, hyperactivity, and panic. However, among antipsychotics, the Food and Drug Administration has approved only risperidone and aripiprazole to treat irritability in autism. Among atypical antipsychotics, olanzapine and quetiapine are limited in their use for autism spectrum disorders in children because of high incidences of weight gain and sedation. In comparison, aripiprazole and ziprasidone cause less weight gain and sedation. However, potential QTc interval prolongation with ziprasidone has been reported. Contrary to ziprasidone, no changes were evident in the QT interval in any of the trials for aripiprazole. However, head-to-head comparison studies are needed to support that aripiprazole may be a promising drug that can be used to treat irritability in autistic children. On the other hand, risperidone has the greatest amount of evidence supporting it, including randomized controlled trials; thus, its efficacy and tolerability has been established in comparison with other agents. Further studies with risperidone as a control drug are needed.

  13. Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis

    PubMed Central

    Beugnet, Frédéric; Halos, Lénaïg; Larsen, Diane; de Vos, Christa

    2016-01-01

    The efficacy of oral treatment with a chewable tablet containing afoxolaner 2.27% w/w (NexGard®, Merial) administered orally was assessed in eight dogs diagnosed with generalised demodicosis and compared with efficacy in eight dogs under treatment with a topical combination of imidacloprid/moxidectin (Advocate®, Bayer). Afoxolaner was administered at the recommended dose (at least 2.5 mg/kg) on Days 0, 14, 28 and 56. The topical combination of imidacloprid/moxidectin was given at the same intervals at the recommended concentration. Clinical examinations and deep skin scrapings were performed every month in order to evaluate the effect on mite numbers and the resolution of clinical signs. The percentage reductions of mite counts were 99.2%, 99.9% and 100% on Days 28, 56 and 84, respectively, in the afoxolaner-treated group, compared to 89.8%, 85.2% and 86.6% on Days 28, 56 and 84 in the imidacloprid/moxidectin-treated group. Skin condition of the dogs also improved significantly from Day 28 to Day 84 in the afoxolaner-treated group. Mite reductions were significantly higher on Days 28, 56 and 84 in the afoxolaner-treated group compared to the imidacloprid/moxidectin-treated group. The results of this study demonstrated that afoxolaner, given orally, was effective in treating dogs with generalised demodicosis within a two-month period. PMID:27012161

  14. Efficacy and safety of topical herbal medicine treatment on recurrent aphthous stomatitis: a systemic review

    PubMed Central

    Li, Chun-Lei; Huang, He-Long; Wang, Wan-Chun; Hua, Hong

    2016-01-01

    This study aimed to evaluate the efficacy and safety of topical treatment with natural herbal medicines on recurrent aphthous stomatitis (RAS). Nine electronic databases were searched to identify the randomized controlled trials and clinical controlled trials that reported the potential effect of natural herbal medicines on RAS published in Chinese or English. Ulcer size and duration, and remission of pain were assessed as main outcome measures. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systemic Review of Interventions and Rev Man software. Thirteen trials with a total of 1,515 patients were included in the present analysis, which showed that topical treatment with natural herbal medicines seemed to benefit RAS patients by reducing ulcer size, shortening ulcer duration, and relieving pain without severe side effects. In conclusion, there is some evidence of the efficacy of topically applied natural herbal medicines with regards to improved RAS outcome measures and fewer side effects. However, given the limitations of this study, the evidence remains insufficient. Well-designed and high-quality randomized controlled trials are required for further exploration. PMID:26770058

  15. Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.

    PubMed

    Aliprandi, P; Castelli, C; Bernorio, S; Dell'Abate, E; Carrara, M

    2004-01-01

    The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile.

  16. Efficacy and safety of topical herbal medicine treatment on recurrent aphthous stomatitis: a systemic review.

    PubMed

    Li, Chun-Lei; Huang, He-Long; Wang, Wan-Chun; Hua, Hong

    2016-01-01

    This study aimed to evaluate the efficacy and safety of topical treatment with natural herbal medicines on recurrent aphthous stomatitis (RAS). Nine electronic databases were searched to identify the randomized controlled trials and clinical controlled trials that reported the potential effect of natural herbal medicines on RAS published in Chinese or English. Ulcer size and duration, and remission of pain were assessed as main outcome measures. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systemic Review of Interventions and Rev Man software. Thirteen trials with a total of 1,515 patients were included in the present analysis, which showed that topical treatment with natural herbal medicines seemed to benefit RAS patients by reducing ulcer size, shortening ulcer duration, and relieving pain without severe side effects. In conclusion, there is some evidence of the efficacy of topically applied natural herbal medicines with regards to improved RAS outcome measures and fewer side effects. However, given the limitations of this study, the evidence remains insufficient. Well-designed and high-quality randomized controlled trials are required for further exploration. PMID:26770058

  17. Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach

    PubMed Central

    Christophi, George P; Rengarajan, Arvind; Ciorba, Matthew A

    2016-01-01

    Ulcerative colitis (UC) is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis) that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam) of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side-effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2) after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5). However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations. PMID:27274301

  18. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia

    PubMed Central

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness. PMID:26937205

  19. Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia.

    PubMed

    Bhusal, Santosh; Diomampo, Sherilyn; Magrey, Marina N

    2016-01-01

    Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness.

  20. Levocloperastine in the treatment of chronic nonproductive cough: comparative efficacy versus standard antitussive agents.

    PubMed

    Aliprandi, P; Castelli, C; Bernorio, S; Dell'Abate, E; Carrara, M

    2004-01-01

    The medical and social impact of cough is substantial. Current antitussive agents at effective doses have adverse events such as drowsiness, nausea and constipation that limit their use. There is also recent evidence that standard antitussive agents, such as codeine, may not reduce cough during upper respiratory infections. Therefore, there is a need for more effective and better-tolerated agents. The efficacy of levocloperastine, a novel antitussive, which acts both centrally on the cough center and on peripheral receptors in the tracheobronchial tree in treating chronic cough, was compared with that of other standard antitussive agents (codeine, levodropropizine and DL-cloperastine) in six open clinical trials. The studies enrolled patients of all ages with cough associated with various respiratory disorders including bronchitis, asthma, pneumonia and chronic obstructive pulmonary disease. Levocloperastine significantly improved cough symptoms (intensity and frequency of cough) in all trials, and improvements were observed after the first day of treatment. In children, levocloperastine reduced nighttime awakenings and irritability, and in adults it was effective in treating cough induced by angiotensin-converting enzyme inhibitors. When compared with other antitussive agents, levocloperastine had improved or comparable efficacy, with a more rapid onset of action. Importantly, no evidence of central adverse events was recorded with levocloperastine, whereas drowsiness was reported by a significant number of patients receiving codeine. Levocloperastine is an effective antitussive agent for the treatment of cough in patients of all ages. It has a more rapid onset of action than standard agents with an improved tolerability profile. PMID:15553659

  1. Chiari malformation and central sleep apnea syndrome: efficacy of treatment with adaptive servo-ventilation*

    PubMed Central

    do Vale, Jorge Marques; Silva, Eloísa; Pereira, Isabel Gil; Marques, Catarina; Sanchez-Serrano, Amparo; Torres, António Simões

    2014-01-01

    The Chiari malformation type I (CM-I) has been associated with sleep-disordered breathing, especially central sleep apnea syndrome. We report the case of a 44-year-old female with CM-I who was referred to our sleep laboratory for suspected sleep apnea. The patient had undergone decompressive surgery 3 years prior. An arterial blood gas analysis showed hypercapnia. Polysomnography showed a respiratory disturbance index of 108 events/h, and all were central apnea events. Treatment with adaptive servo-ventilation was initiated, and central apnea was resolved. This report demonstrates the efficacy of servo-ventilation in the treatment of central sleep apnea syndrome associated with alveolar hypoventilation in a CM-I patient with a history of decompressive surgery. PMID:25410846

  2. Efficacy of oxfendazole for the treatment of giardiosis in dogs. Experiments in dog breeding kennels.

    PubMed

    Villeneuve, V; Beugnet, F; Bourdoiseau, G

    2000-09-01

    Giardiosis is one of the most frequent parasites of dogs and cats. Since several years, the treatment is based on the use of metronidazole. A coproscopic study in four dog kennels was conducted to demonstrate, at a significant level, the efficacy of oxfendazole (Dolthène, Merial). At the posology of 11.3 mg/kg each day during three days (D1, D2 and D3), no dogs eliminated Giardia cysts and all dogs are clinically cured. The importance of hygienic measures is underlined. In kennels 1 and 2 where hygienic conditions were poor, dogs reexcreted cysts again after treatment. In kennels where the boxes were disinfected, no dogs, treated with 22.6 or 11.3 mg/kg, reexcreted Giardia cysts.

  3. Efficacy of microwave ablation for the treatment of endometrial carcinoma: A report of 3 cases

    PubMed Central

    NAKAMURA, KOHEI; NAKAYAMA, KENTARO; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; ISHIBASHI, TOMOKA; SATO, EMI; AMANO, CHIKA; KYO, SATORU

    2016-01-01

    Microwave endometrial ablation (MEA) is effective for the emergency control of uterine hemorrhage. However, to the best of our knowledge, there has been only a single report of life-threatening hemorrhage induced by endometrial carcinoma that was treated with MEA. The present report evaluates the efficacy of MEA as an emergency therapeutic option for the control of bleeding due to advanced endometrial carcinoma and minimally-invasive, early-stage endometrial carcinoma in 3 patients. MEA was able to effectively control massive uterine bleeding due to endometrial carcinoma in 2 patients with advanced disease and was curative in a patient with minimally-invasive endometrial carcinoma. Given its safety, simplicity and effectiveness, MEA may be utilized for the emergency treatment of uterine bleeding in advanced endometrial carcinoma, and may be used as a curative treatment in early-stage endometrial carcinoma. PMID:27123057

  4. Treatment of substance abuse by relaxation training: a review of its rationale, efficacy and mechanisms.

    PubMed

    Klajner, F; Hartman, L M; Sobell, M B

    1984-01-01

    The efficacy of relaxation training as a treatment for alcohol and drug abuse is reviewed, and directions for future research derived. Such use of relaxation procedures, notably progressive muscular relaxation and meditation, has been widespread and is premised on the assumptions that substance abuse is causally linked to anxiety and that anxiety can be reduced by relaxation training. However, the evidence suggests that such precipitating anxiety is limited to interpersonal-stress situations involving diminished perceived personal control over the stressor, and that alcohol and other drugs are often consumed for their euphoric rather than tranquilizing effects. Consequently, the empirical support for the effectiveness of relaxation training as a treatment for substance abuse in general is equivocal. As well, the existing outcome studies suffer from numerous methodological and conceptual inadequacies. In cases of demonstrated effectiveness, increased perceived control is a more plausible explanation than is decreased anxiety.

  5. The safety, tolerability and efficacy of pimavanserin tartrate in the treatment of psychosis in Parkinson's disease.

    PubMed

    Hermanowicz, Stefan; Hermanowicz, Neal

    2016-06-01

    Parkinson's disease psychosis (PDP) is a common and often very disturbing component of Parkinson's disease (PD). PDP consists of hallucinations that are mainly visual and delusions that are often of a paranoid nature. These symptoms can be the most troubling and disruptive of all the manifestations of Parkinson's disease. Current treatment methods include the reduction of anti-Parkinson's medications, a strategy that may worsen the motor problems the medications are prescribed to alleviate, and the introduction of selected antipsychotic medications that carry with them the potential for troubling side effects and serious consequences. Pimavanserin has been developed and studied in clinical trials to specifically address Parkinson's disease psychosis and has been submitted to the U.S. Food and Drug Administration for its approval for this purpose. If this is granted, we believe the evidence of Pimavanserin efficacy, safety and tolerability will position this medication as the first choice for treatment of Parkinson's disease psychosis.

  6. [Clinicobiochemical and immunological assessment of polyoxidonium efficacy in the treatment of patients with chronic calculous pyelonephritis].

    PubMed

    Kazeko, N I; Khil'kevich, S V

    2011-01-01

    Of 59 patients with chronic calculous pyelonephritis (CCP) taking preparation therapy for extracorporeal lithotripsy, 29 patients received combined basic treatment (antibacterial drugs, phytotherapy, physiotherapy) plus polyoxidonium (a course of 10 intramuscular 6 mg injections each other day). The rest 30 patients (controls) received basic therapy alone. Polyoxidonium efficacy was assessed by the results of clinical, device and immunological investigations, content of the main phospholipid fractions and cholesterol in red cell membranes. The results of the tests show that polyoxidonium has anti-inflammatory and immunomodulating effects, exhibits activity of peroxidation processes, contributes to normalization of a lipid phase of cell membranes and can be recommended as a component of combined treatment of patients with chronic pyelonephritis and urolithiasis. PMID:22448475

  7. Prediction of treatment efficacy for prostate cancer using a mathematical model

    PubMed Central

    Peng, Huiming; Zhao, Weiling; Tan, Hua; Ji, Zhiwei; Li, Jingsong; Li, King; Zhou, Xiaobo

    2016-01-01

    Prostate immune system plays a critical role in the regulation of prostate cancer development regarding androgen-deprivation therapy (ADT) and/or immunotherapy (vaccination). In this study, we developed a mathematical model to explore the interactions between prostate tumor and immune microenvironment. This model was used to predict treatment outcomes for prostate cancer with ADT, vaccination, Treg depletion and/or IL-2 neutralization. Animal data were used to guide construction, parameter selection, and validation of our model. Our analysis shows that Treg depletion and/or IL-2 neutralization can effectively improve the treatment efficacy of combined therapy with ADT and vaccination. Treg depletion has a higher synergetic effect than that from IL-2 neutralization. This study highlights a potential therapeutic strategy in effectively managing prostate tumor growth and provides a framework of systems biology approach in studying tumor-related immune mechanism and consequent selection of therapeutic regimens. PMID:26868634

  8. Investigating the efficacy of bisphosphonates treatment against multiple myeloma induced bone disease using a computational model.

    PubMed

    Ji, Bing; Yang, Qing; Genever, Paul G; Fagan, Michael J

    2014-01-01

    Multiple myeloma (MM)-induced bone disease is mortal for most MM patients. Bisphosphonates are first-line treatment for MM-induced bone disease, since it can inhibit osteoclast activity and the resultant bone resorption by suppressing the differentiation of osteoclast precursors into mature osteoclasts, promoting osteoclast apoptosis and disrupting osteoclast function. However, it is still unclear whether bisphosphonates have an anti-tumour effect. In our previous work, a computational model was built to simulate the pathology of MM-induced bone disease. This paper extends this proposed computational model to investigate the efficacy of bisphosphonates treatment and then clear the controversy of this therapy. The extended model is validated through the good agreement between simulation results and experimental data. The simulation results suggest that bisphosphonates indeed have an anti-tumour effect.

  9. Activation of multiple chemotherapeutic prodrugs by the natural enzymolome of tumour-localised probiotic bacteria.

    PubMed

    Lehouritis, Panos; Stanton, Michael; McCarthy, Florence O; Jeavons, Matthieu; Tangney, Mark

    2016-01-28

    Some chemotherapeutic drugs (prodrugs) require activation by an enzyme for efficacy. We and others have demonstrated the ability of probiotic bacteria to grow specifically within solid tumours following systemic administration, and we hypothesised that the natural enzymatic activity of these tumour-localised bacteria may be suitable for activation of certain such chemotherapeutic drugs. Several wild-type probiotic bacteria; Escherichia coli Nissle, Bifidobacterium breve, Lactococcus lactis and Lactobacillus species, were screened against a panel of popular prodrugs. All strains were capable of activating at least one prodrug. E. coli Nissle 1917 was selected for further studies because of its ability to activate numerous prodrugs and its resistance to prodrug toxicity. HPLC data confirmed biochemical transformation of prodrugs to their toxic counterparts. Further analysis demonstrated that different enzymes can complement prodrug activation, while simultaneous activation of multiple prodrugs (CB1954, 5-FC, AQ4N and Fludarabine phosphate) by E. coli was confirmed, resulting in significant efficacy improvement. Experiments in mice harbouring murine tumours validated in vitro findings, with significant reduction in tumour growth and increase in survival of mice treated with probiotic bacteria and a combination of prodrugs. These findings demonstrate the ability of probiotic bacteria, without the requirement for genetic modification, to enable high-level activation of multiple prodrugs specifically at the site of action. PMID:26655063

  10. Efficacy of Fentanyl Transdermal Patch in the Treatment of Chronic Soft Tissue Cancer Pain

    PubMed Central

    Hemati, Karim; Zaman, Behrooz; Hassani, Valliolah; Imani, Farnad; Dariaie, Parviz

    2015-01-01

    Background: Cancer pain may be a major problem for health care providers worldwide. According to different studies reporting the pain severity, one-third of patients reported to have moderate to severe pain. Management of cancer pain is one of the most important goals of palliative care. Recently, different research results on the efficacy of opioid analgesics in chronic pain management have played a role to implement standards in pain control by government agencies worldwide. Objectives: This study aimed to investigate the efficacy of fentanyl transdermal patch in the treatment of chronic soft tissue cancer pain. Patients and Methods: In a prospective descriptive study, we evaluated 86 patients with soft tissue tumors with chronic pain referred to cancer institute of Imam Khomeini Hospital, Tehran, Iran, during 2006-2007. For all patients, transdermal fentanyl patch (25 μg/h) was administered. The appearance of patches was the same. Pain severity was measured by Visual Analogue Scale (VAS) initially and 24, 48 and 72 hours after the initiation of treatment. Results: Patients' characteristics and VAS score before the treatment were not significantly different (P > 0.05). According to our findings, the pain severity was significantly reduced after the treatment (P = 0.001). The incidence of adverse events in patients was significantly high (72%). The most common adverse events were sleepiness, nausea and vomiting in 30.2% and 18.6%, respectively. Conclusions: Transdermal fentanyl patch was an effective and safe method to reduce pain in patients with soft tissue tumors. Moreover, it could improve the quality of life in these patients, but adverse events occurred in approximately 72% of patients. PMID:25789240

  11. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

    PubMed Central

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  12. Safety and efficacy of aneurysm treatment with WEB: results of the WEBCAST study.

    PubMed

    Pierot, Laurent; Costalat, Vincent; Moret, Jacques; Szikora, Istvan; Klisch, Joachim; Herbreteau, Denis; Holtmannspötter, Markus; Weber, Werner; Januel, Anne-Christine; Liebig, Thomas; Sychra, Vojtech; Strasilla, Christoph; Cognard, Christophe; Bonafé, Alain; Molyneux, Andrew; Byrne, James V; Spelle, Laurent

    2016-05-01

    OBJECT WEB is an innovative intrasaccular treatment for intracranial aneurysms. Preliminary series have shown good safety and efficacy. The WEB Clinical Assessment of Intrasaccular Aneurysm Therapy (WEBCAST) trial is a prospective European trial evaluating the safety and efficacy of WEB in wide-neck bifurcation aneurysms. METHODS Patients with wide-neck bifurcation aneurysms for which WEB treatment was indicated were included in this multicentergood clinical practices study. Clinical data including adverse events and clinical status at 1 and 6 months were collected and independently analyzed by a medical monitor. Six-month follow-up digital subtraction angiography was also performed and independently analyzed by a core laboratory. Success was defined at 6 months as complete occlusion or stable neck remnant, no worsening in angiographic appearance from postprocedure, and no retreatment performed or planned. RESULTS Ten European neurointerventional centers enrolled 51 patients with 51 aneurysms. Treatment with WEB was achieved in 48 of 51 aneurysms (94.1%). Adjunctive implants (coils/stents) were used in 4 of 48 aneurysms (8.3%). Thromboembolic events were observed in 9 of 51 patients (17.6%), resulting in a permanent deficit (modified Rankin Scale [mRS] Score 1) in 1 patient (2.0%). Intraoperative rupture was not observed. Morbidity (mRS score > 2) and mortality were 2.0% (1 of 51 patients, related to rupture status on entry to study) and 0.0% at 1 month, respectively. Success was achieved at 6 months in 85.4% of patients treated with WEB: 23 of 41 patients (56.1%) had complete occlusion, 12 of 41 (29.3%) had a neck remnant, and 6 of 41 (14.6%) had an aneurysm remnant. CONCLUSIONS The WEBCAST study showed good procedural and short-term safety of aneurysm treatment with WEB and good 6-month anatomical results.

  13. Evaluation of the therapeutic efficacy of Mentha crispa in the treatment of giardiasis.

    PubMed

    Teles, Naracélia S B; Fechine, Francisco V; Viana, Fernando André C; Viana, Ismenia O L; Nascimento, Demétrius F; Leite, Ana Lourdes A S; Bezerra, Fernando Antônio Frota; Moraes, Manoel Odorico; Moraes, Maria Elisabete A

    2011-11-01

    It's estimated that around 200 million people are annually infected with Giardia lamblia, making the disease a major cause of morbidity worldwide. The current treatment of giardiasis includes the use of several drugs, among them, herbal medicines formulated with Mentha crispa. Thus, the purpose of this study was to evaluate the therapeutic efficacy of M. crispa in the treatment of giardiasis. The research consisted initially of a cross-sectional study for the selection of subjects with giardiasis. After that, there was a randomized, open, in parallel with active control study, in order to verify the therapeutic efficacy of M. crispa in the treatment of giardiasis. Coprology samples were collected from 1622 patients between May 2005 and May 2007 for a series of parasitological examinations. Ninety-six patients with G. lamblia were selected, which were then distributed randomly into two groups: Secnidazole, consisting of 50 patients treated with 2g of Secnidazole and M. crispa, containing 46 patients treated with 2g of M. crispa. After 7 days, healing was evaluated by enzyme immunoassay in a fresh fecal sample. Additionally, the subjects were questioned about possible adverse effects and answered a questionnaire covering socioeconomic and hydrosanitary issues. The analysis of the clinical trial data showed that the cure rate for the Secnidazole group (84.0%) was significantly higher (P=0.0002) as that verified in the M. crispa group (47.83%). Therefore, the study concludes that, in the dose used in this trial, the effect of M. crispa in the treatment of giardisis is less effective than that of Secnidazole. PMID:21872682

  14. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice.

    PubMed

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie; Wang, Xin-Chun; Peng, Xin-Yu

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  15. Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy.

    PubMed

    Spencer, John S; Duthie, Malcolm S; Geluk, Annemieke; Balagon, Marivic F; Kim, Hee Jin; Wheat, William H; Chatterjee, Delphi; Jackson, Mary; Li, Wei; Kurihara, Jade N; Maghanoy, Armi; Mallari, Irene; Saunderson, Paul; Brennan, Patrick J; Dockrell, Hazel M

    2012-12-01

    Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment

  16. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    PubMed

    Bao, Jiaolin; Huang, Borong; Zou, Lidi; Chen, Shenghui; Zhang, Chao; Zhang, Yulin; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao; He, Chengwei

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer. PMID:26421434

  17. Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

    PubMed

    Bao, Jiaolin; Huang, Borong; Zou, Lidi; Chen, Shenghui; Zhang, Chao; Zhang, Yulin; Chen, Meiwan; Wan, Jian-Bo; Su, Huanxing; Wang, Yitao; He, Chengwei

    2015-01-01

    Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM) promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM) inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU), camptothecin (CPT), and paclitaxel (TAX). The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

  18. Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells.

    PubMed

    Zhang, Zhongyuan; Teruya, Kiichiro; Yoshida, Toshihiro; Eto, Hiroshi; Shirahata, Sanetaka

    2013-01-09

    Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH) levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

  19. A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma.

    PubMed

    Nishikawa, Sho; Tanaka, Akane; Matsuda, Akira; Oida, Kumiko; Jang, Hyosun; Jung, Kyungsook; Amagai, Yosuke; Ahn, Ginae; Okamoto, Noriko; Ishizaka, Saori; Matsuda, Hiroshi

    2014-04-01

    Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma.

  20. From Ideas to Efficacy: The ORBIT Model for Developing Behavioral Treatments for Chronic Diseases

    PubMed Central

    Czajkowski, Susan M.; Powell, Lynda H.; Adler, Nancy; Naar-King, Sylvie; Reynolds, Kim D.; Hunter, Christine M.; Laraia, Barbara; Olster, Deborah H.; Perna, Frank M.; Peterson, Janey C.; Epel, Elissa; Boyington, Josephine E.; Charlson, Mary E.

    2015-01-01

    Objective Given the critical role of behavior in preventing and treating chronic diseases, it is important to accelerate the development of behavioral treatments that can improve chronic disease prevention and outcomes. Findings from basic behavioral and social science research hold great promise for addressing behaviorally-based clinical health problems, yet there is currently no established pathway for translating fundamental behavioral science discoveries into health-related treatments ready for Phase III efficacy testing. This article provides a systematic framework for guiding efforts to translate basic behavioral science findings into behavioral treatments for preventing and treating chronic illness. Methods The ORBIT model for behavioral treatment development is described as involving a flexible and progressive process, pre-specified clinically significant milestones for forward movement, and return to earlier stages for refinement and optimization. Results This article presents the background and rationale for the ORBIT model, a summary of key questions for each phase, a selection of study designs and methodologies well-suited to answering these questions, and pre-specified milestones for forward or backward movement across phases. Conclusions The ORBIT model provides a progressive, clinically-relevant approach to increasing the number of evidence-based behavioral treatments available to prevent and treat chronic diseases. PMID:25642841

  1. Clinical Efficacy of Blue Light Full Body Irradiation as Treatment Option for Severe Atopic Dermatitis

    PubMed Central

    Becker, Detlef; Seemann, Gunda; Fell, Isabel; Saloga, Joachim; Grabbe, Stephan; von Stebut, Esther

    2011-01-01

    Background Therapy of atopic dermatitis (AD) relies on immunosuppression and/or UV irradiation. Here, we assessed clinical efficacy and histopathological alterations induced by blue light-treatment of AD within an observational, non-interventional study. Methodology/Principal Findings 36 patients with severe, chronic AD resisting long term disease control with local corticosteroids were included. Treatment consisted of one cycle of 5 consecutive blue light-irradiations (28.9 J/cm2). Patients were instructed to ask for treatment upon disease exacerbation despite interval therapy with topical corticosteroids. The majority of patients noted first improvements after 2–3 cycles. The EASI score was improved by 41% and 54% after 3 and 6 months, respectively (p≤0.005, and p≤0.002). Significant improvement of pruritus, sleep and life quality was noted especially after 6 months. Also, frequency and intensity of disease exacerbations and the usage of topical corticosteroids was reduced. Finally, immunohistochemistry of skin biopsies obtained at baseline and after 5 and 15 days revealed that, unlike UV light, blue light-treatment did not induce Langerhans cell or T cell depletion from skin. Conclusions/Significance Blue light-irradiation may represent a suitable treatment option for AD providing long term control of disease. Future studies with larger patient cohorts within a randomized, placebo-controlled clinical trial are required to confirm this observation. PMID:21687679

  2. A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence

    PubMed Central

    Guerrini, Irene; Gentili, Claudio; Nelli, Gloria; Guazzelli, Mario

    2006-01-01

    Background We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit – University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. Results At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). Conclusion Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol. PMID:17176456

  3. Quantitative analysis of nuclear shape in oral squamous cell carcinoma is useful for predicting the chemotherapeutic response.

    PubMed

    Ogura, Maki; Yamamoto, Yoichiro; Miyashita, Hitoshi; Kumamoto, Hiroyuki; Fukumoto, Manabu

    2016-06-01

    The number of people afflicted with oral carcinoma in Japan has increased in recent years. Although preoperative neoadjuvant therapy with cisplatin and 5-fluorouracil are performed, chemotherapeutic response varies widely among the patients. With the aim of establishing novel indices to predict the therapeutic response to chemotherapy, we investigated the relationship between morphological features of pre-treatment oral carcinoma nuclei and the chemotherapeutic response using quantifying morphology of cell nuclei in pathological specimen images. We measured 4 morphological features of the nucleus of oral squamous cell carcinoma cases classified by the response to chemotherapy: No Change (NC) group, Partial Response (PR) group and Complete Response (CR) group. Furthermore, we performed immunohistochemical staining for p53 and Ki67 and calculated their positive rates in cancer tissues. Compactness and symmetry of the nucleus were significantly higher and nuclear edge response was significantly lower in cancer cells with lower chemotherapeutic responses compared high chemotherapeutic responders. As for positive rates of p53 and Ki67, there were no significant differences between any of the response groups. Morphological features of cancer cell nuclei in pathological specimens are sensitive predictive factors for the chemotherapeutic response to oral squamous cell carcinoma.

  4. Chemotherapeutic agents for GI tumor chemoradiotherapy overview of chemotherapeutic agents to be combined with radiotherapy in the GI tract and their potential as radiosensitizers.

    PubMed

    Klautke, G; Müller, K

    2016-08-01

    In the treatment of gastrointestinal tumors, simultaneous radiochemotherapy plays an important role. It is one of the principles of simultaneous radiochemotherapy, applying only chemotherapeutic agents simultaneously to radiation, which are primarily effective in the treated tumor entity, therefore a lot of different agents, like antimetabolites, mostly 5-fluorouracil, platinum derivates (mostly cisplatinum and oxaliplatin), mitomycin C and taxanes are used in simultaneous radiochemotherapy. Most of these have also radiation-intensifying effects. The mechanisms and interactions with ionizing radiation are presented in the article. PMID:27644902

  5. Disulfiram Efficacy in the Treatment of Alcohol Dependence: A Meta-Analysis

    PubMed Central

    Skinner, Marilyn D.; Lahmek, Pierre; Pham, Héloïse; Aubin, Henri-Jean

    2014-01-01

    Background Despite its success with compliant or supervised patients, disulfiram has been a controversial medication in the treatment of alcoholism. Often, study designs did not recognize a pivotal factor in disulfiram research, the importance of an open-label design. Our objectives are: (1) to analyze the efficacy and safety of disulfiram in RCTs in supporting abstinence and (2) to compare blind versus open-label studies, hypothesizing that blinded studies would show no difference between disulfiram and control groups because the threat would be evenly spread across all groups. Methods and Findings We searched PubMed, EMBASE and the Cochrane Central Register for RCTs on disulfiram use with alcoholics in comparison to any alcoholic control group. The primary outcome was defined by the authors of each trial. Additional analyses included: blind vs. open-label, with or without supervision, cocaine study or not, and type of control. Overall, the 22 included studies showed a higher success rate of disulfiram compared to controls Hedges'g = .58 (95%CI = .35–.82). When comparing blind and open-label RCTs, only open-label trials showed a significant superiority over controls g = .70 (95%CI = .46–.93). RCTs with blind designs showed no efficacy of disulfiram compared to controls. Disulfiram was also more effective than the control condition when compared to naltrexone g = .77, 95%CI = .52–1.02, to acamprosate g = .76, 95%CI = .04–1.48, and to the no disulfiram groups g = .43, 95%CI = .17–.69. Limits include: (1) a population of 89% male subjects and (2) a high but unavoidable heterogeneity of the studies with a substantial I-square in most subgroups of studies. Conclusions Blinded studies were incapable of distinguishing a difference between treatment groups and thus are incompatible with disulfiram research. Based on results with open-label studies, disulfiram is a safe and efficacious treatment compared to other abstinence

  6. The Efficacy of a Condensed "Seeking Safety" Intervention for Women in Residential Chemical Dependence Treatment at 30 Days Posttreatment

    ERIC Educational Resources Information Center

    Cash Ghee, Anna; Bolling, Lanny C.; Johnson, Candace S.

    2009-01-01

    This study examined the efficacy of a condensed version of the "Seeking Safety" intervention in the reduction of trauma-related symptoms and improved drug abstinence rates among women in residential chemical dependence treatment. One hundred and four women were randomly assigned to treatment including a condensed (six session) "Seeking Safety"…

  7. Occurrence and efficacy of bisphenol A (BPA) treatment in selected municipal wastewater treatment plants, Bangkok, Thailand.

    PubMed

    Pookpoosa, Intira; Jindal, Ranjna; Morknoy, Daisy; Tantrakarnapa, Kraichat

    2015-01-01

    Investigations were carried out on the occurrence and fate of bisphenol A (BPA) in five wastewater treatment plants (WWTPs) in Bangkok, namely, Rattanakosin, Chong Non Si, Din Daeng (DD), Nong Khaem and Thungkru (TK) during three sampling events between October 2013 and February 2014. Based on the results, the influent and effluent BPA concentrations ranged between 128.5 ng/L and 606.0 ng/L; and 38.7 ng/L and 270.5 ng/L, respectively. The effluent BPA concentrations of most of the five WWTPs were lower than the influent levels. TK had the highest removal efficiency in October 2013 (80.4%) and December 2013 (90.7%) and the second highest in February 2014 (69.2%). DD had the highest removal efficiency in February 2014 (91.8%). The treatment processes employed at TK and DD were vertical loop reactor activated sludge process and activated sludge with nutrients removal, respectively. Thus, these processes seem to be good for BPA degradation.

  8. The Efficacy of Zinc Administration in the Treatment of Primary Dysmenorrhea

    PubMed Central

    Teimoori, Batool; Ghasemi, Marzieh; Hoseini, Zeinab Sadat Amir; Razavi, Maryam

    2016-01-01

    Objectives Dysmenorrhea is a common complaint in women. Primary dysmenorrhea is defined as painful menstruation in the absence of pelvic disease and is caused by uterine contractions caused by prostaglandins released from the endometrium. Conventional treatments include nonsteroidal anti-inflammatory drugs and oral contraceptives. We sought to evaluate the efficacy of zinc supplementation in the treatment of primary dysmenorrhea.  Methods Two-hundred participants with primary dysmenorrhea were randomized into one of two groups. The intervention group received zinc and mefenamic acid, and the control group received mefenamic acid and a placebo drug. After three months of treatment, changes in the incidence of dysmenorrhea and the degree of pain were measured in both groups.  Results The mean pain score before administration of zinc and mefenamic acid in the intervention group was 5.3±1.8 and after treatment was 1.2±1.9 (p < 0.001). In the control group, the mean pain score before administration of mefenamic acid and placebo was 5.8±2.1 and after treatment was 2.9±2.6 (p < 0.001). The difference in pain levels before and after treatment in the intervention group was 4.1±2.8, and in the control group was 2.9±1.7 (p > 0.050). We also found that 64% of case group and 33% of the control group did not experience dysmenorrhea after treatment (p < 0.001).  Conclusions The use of a zinc supplement in combination with mefenamic acid was superior in reducing primary dysmenorrhea compared to mefenamic acid alone. PMID:27168920

  9. Ultrasound and 3D Skin Imaging: Methods to Evaluate Efficacy of Striae Distensae Treatment

    PubMed Central

    Bleve, Mariella; Capra, Priscilla; Pavanetto, Franca; Perugini, Paola

    2012-01-01

    Background. Over time, the striae rubra develop into striae alba that appear white, flat, and depressed. It is very important to determine the optimum striae management. In order to evaluate the effectiveness of these therapies, objective measurement tools are necessary. Objective. The aim of this study is to evaluate if ultrasonography and PRIMOS can be used to obtain an objective assessment of stretch marks type and stage; furthermore, we aim to apply these techniques to evaluate the efficacy of a topical treatment. Methods. 20 volunteers were enrolled with a two-month study. A marketed cosmetic product was used as the active over one body area. The controlateral area with stretch marks was treated with a “placebo” formulation without active, as a control. The instrumental evaluation was carried out at the beginning of the trial (baseline values or t0), after 1 month (t1), and at the end of the study (t2). Results. PRIMOS was able to measure and document striae distensae maturation; furthermore, ultrasound imaging permitted to visualize and diagnose the striae. Statistical analysis of skin roughness demonstrated a statistically significant reduction of Rp value only in a treated group. In fact, the Rp value represented a maximum peak height in the area selected. These results demonstrated that after two months of treatment only the striae rubra can be treated successfully. Conclusions. This work demonstrated that the 22MHz ultrasound can diagnose stretch marks; PRIMOS device can detect and measure striae distensae type and maturation. Furthermore, the high-frequency ultrasound and the 3D image device, described in this work, can be successfully employed in order to evaluate the efficacy of a topical treatment. PMID:22203840

  10. Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety.

    PubMed

    Litten, Raye Z; Wilford, Bonnie B; Falk, Daniel E; Ryan, Megan L; Fertig, Joanne B

    2016-01-01

    Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds. PMID:26928397

  11. Potential medications for the treatment of alcohol use disorder: An evaluation of clinical efficacy and safety.

    PubMed

    Litten, Raye Z; Wilford, Bonnie B; Falk, Daniel E; Ryan, Megan L; Fertig, Joanne B

    2016-01-01

    Alcohol use disorder (AUD), as currently defined in the Diagnostic and Statistical Manual, 5th Edition (DSM-5), is a heterogeneous disorder stemming from a complex interaction of neurobiological, genetic, and environmental factors. As a result of this heterogeneity, there is no one treatment for AUD that will work for everyone. During the past 2 decades, efforts have been made to develop a menu of medications to give patients and clinicians more choices when seeking a therapy that is both effective and which has limited side effects. To date, 3 medications have been approved by the US Food and Drug Administration (FDA) to treat alcohol dependence: disulfiram, naltrexone, and acamprosate. In addition to these approved medications, researchers have identified new therapeutic targets and, as a result, a number of alternative medications are now being evaluated for treatment of AUD in human studies. Although not approved by the FDA for the treatment of AUD, in some cases, these alternative medications are being used off-label by clinicians for this purpose. These potential medications are reviewed here. They include nalmefene, varenicline, gabapentin, topiramate, zonisamide, baclofen, ondansetron, levetiracetam, quetiapine, aripiprazole, and serotonin reuptake inhibitors. The effectiveness of these medications has been mixed-some show good efficacy with side effects that are mild to moderate in intensity; others have mixed or promising results but are awaiting findings from ongoing studies; and still others show poor efficacy, despite promising preliminary results. Medications development remains a high priority. Key initiatives for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) include supporting the discovery and development of more effective and safer medications, advancing the field of personalized medicine, and forging public and private partnerships to investigate new and more effective compounds.

  12. Efficacy of a brief treatment for nightmares and sleep disturbances for veterans.

    PubMed

    Balliett, Noelle E; Davis, Joanne L; Miller, Katherine E

    2015-11-01

    Nightmares and sleep disturbances are common complaints among military Veterans (Plumb & Zelman, 2009) and may be difficult to eradicate (Forbes, Phelps, & McHugh, 2001). A treatment protocol (Exposure, Relaxation, and Rescription Therapy [ERRT]) targeting nightmares and sleep disturbances, which has been used effectively in civilian populations, was adapted for the military (ERRT-M). A pilot study evaluated the efficacy of ERRT-M in improving sleep quality and quantity and reducing nightmares, symptoms of posttraumatic stress disorder, and depression in a trauma-exposed, Veteran sample (N = 19). At 1 week after treatment, analyses revealed improvements in nightmare frequency and severity, depression, sleep quality, and insomnia severity. Treatment gains were maintained at a 2-month follow-up. Fifty percent of the sample was considered treatment responders (i.e., no nightmares in the previous week). Results of this pilot study suggest that directly targeting sleep and nightmares is successful in alleviating sleep disturbances and related psychopathology in some Veterans. PMID:26010113

  13. The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity.

    PubMed

    Tastekin, Didem; Tambas, Makbule; Kilic, Kemal; Erturk, Kayhan; Arslan, Deniz

    2014-12-01

    This open-labeled phase II, efficacy-finding study evaluated the efficiency and safety of Pistacia terebinthus soap in metastatic colorectal cancer patients who developed cetuximab induced skin toxicity. Patients who received cetuximab plus chemotherapy and developed Grade 2 or 3 skin toxicity were treated twice daily with a soap made of oil extracted from Pistacia terebinthus. During treatment, no topical or oral antibiotics, corticosteroids or other moisturizers were used. Patients were examined 1 week later and their photographs were taken. Fifteen mCRC patients who developed skin toxicity while receiving first-line CTX in combination with chemotherapy were included into the study. Eight patients were male and the median age was 58 (25-70). Sixty percent of the patients (n:9) had Grade 3 skin toxicity. Complete response rates in patients with Grade 2 and Grade 3 skin toxicities were 100 and 33%, respectively. In the remaining patients with Grade 3 toxicity the skin toxicity regressed to Grade 1. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity was necessary. Skin toxicity reoccurred in all patients when patients stopped administering the soap and therefore they used it throughout the cetuximab treatment. Pistacia terebinthus soap seemed to be used safely and effectively in the treatment of skin toxicity induced by Cetuximab.

  14. Preadolescents’ and Parents’ Dietary Coping Efficacy during Behavioral Family-Based Weight Control Treatment¥

    PubMed Central

    Theim, Kelly R.; Sinton, Meghan M.; Stein, Richard I.; Saelens, Brian E.; Thekkedam, Sucheta C.; Welch, R. Robinson; Epstein, Leonard H.; Wilfley, Denise E.

    2012-01-01

    Developmentally relevant high-risk dietary situations (e.g., parties where tempting foods are available) may influence overweight youth’s weight control, as they increase risk for overeating. Better self-efficacy for coping with these situations—which preadolescents may learn from their parents—could foster successful weight control. Overweight preadolescents (N=204) ages 7–12 years (67% female), each with one parent, separately completed the Hypothetical High-Risk Situation Inventory (HHRSI) pre- and post-weight loss treatment. The HHRSI assesses temptation to overeat and confidence in refraining from overeating in response to four high-risk dietary scenarios. Participants generated coping strategies for each scenario. Coping strategies and confidence increased and temptation decreased from pre- to post-weight loss treatment. Parents’ increase in confidence from pre- to post-treatment was associated with preadolescents’ and parents’ weight loss. Tailoring treatments to enhance parents’ coping skills (e.g., building strategies, targeting high temptation/low confidence scenarios) may maximize preadolescents’ weight control. PMID:22081241

  15. Clinical efficacy of combined rituximab treatment in a woman with severe Graves' ophthalmopathy

    PubMed Central

    Liu, Xiaomei; Guo, Hui; Liu, Juan; Shi, Bingyin

    2016-01-01

    The present study reports the case of a female Chinese patient with Graves' disease (GD) and severe Graves' ophthalmopathy (GO) in its active phase, who was treated with propylthiouracil and oral prednisolone for 2 months at a local hospital. However, a lack of improvement in symptoms meant that the patient was transferred to the First Affiliated Hospital of Xi'an Jiaotong University (Xi'an, China), whereupon the patient received high-dose intravenous methylprednisolone pulse therapy, although with limited efficacy. Subsequently, rituximab (RTX; anti-CD20 monoclonal antibody) combined with orbital irradiation treatment was initiated. The patient responded positively to the combined treatment; the clinical symptoms and enlargement of the extraocular muscles were ameliorated, and there were marked decreases in the clinical activity and NOSPECS grading scores. Furthermore, the serum levels of anti-thyrotropin receptor antibodies (TRAb) were markedly decreased at 2 months following RTX therapy. The patient was maintained in a euthyroid state by treatment with methimazole during and following RTX therapy. It was concluded that RTX treatment may attenuate severe GO by depleting lymphocytes, and may promote the recovery of GD by reducing the serum levels of TRAb. PMID:27446325

  16. The efficacy of amoxycillin/clavulanate (Augmentin) in the treatment of severe staphylococcal infections.

    PubMed

    Moreillon, P

    1994-04-01

    The experimental and clinical values of amoxycillin/clavulanate in severe Staphylococcus aureus infections are reviewed. Experimentally, amoxycillin/clavulanate was highly effective in the treatment of acute endocarditis due to methicillin-sensitive isolates of S. aureus (MSSA) in rats. In addition, high doses of amoxycillin/clavulanate also cured experimental endocarditis due to methicillin-resistant strains of S. aureus (MRSA) in the animal model. In the clinical setting, a review of 86 patients with either community- or hospital-acquired bacteraemia due to MSSA showed that intravenous treatment with amoxycillin/clavulanate was adequate for empirical (and apparently also long-term) therapy of such severe infections. However, the retrospective nature of the analysis did not allow assessment of the relative efficacy of amoxycillin/clavulanate as compared with standard anti-staphylococcal drugs, such as flucloxacillin or vancomycin. Further prospective studies are warranted to address this issue. Thus, amoxycillin/clavulanate appears to be a good candidate for empirical treatment of severe infections that may be caused by MSSA. Usage of amoxycillin/clavulanate against MRSA is, however, still experimental and is not currently advocated for the treatment of MRSA infections in humans.

  17. Flexible Ureteroscopy Can Be More Efficacious in the Treatment of Proximal Ureteral Stones in Select Patients

    PubMed Central

    Alkan, Erdal; Sarıbacak, Ali; Ozkanli, Ahmet Oguz; Basar, Mehmet Murad; Acar, Oguz; Balbay, Mevlana Derya

    2015-01-01

    Purpose. We aimed to compare and evaluate the outcomes and complications of two endoscopic treatment procedures, semirigid ureteroscopy (SR-URS) and flexible ureteroscopy (F-URS), in the treatment of proximal ureteral stones (PUS). Methods. SR-URS (group 1) was done on 68 patients whereas 64 patients underwent F-URS (group 2) for the treatment of PUS. Success rate was defined as the absence of stone fragments or presence of asymptomatic insignificant residual fragments < 2 mm. Outcomes and complications were recorded. Results. The differences were statistically not significant in age, gender, body mass index (BMI), and stone characteristics between groups. Mean ureteral stone size was 9.1 ± 0.4 mm and 8.9 ± 0.5 mm for groups 1 and 2. Mean operative time was 34.1 ± 1.5 min and 49.4 ± 2.3 min for groups 1 and 2 (p = 0.001). SFRs were 76.5% and 87.5% for groups 1 and 2 (p = 0.078). Two major complications (ureteral avulsion and ureteral rupture) occurred in group 1. Conclusion. F-URS is safer and less invasive than SR-URS in patients with PUS. There is no statistically significant difference in the efficacy of either technique. Nonetheless we recommend F-URS in the management of PUS as a first-line treatment option in select cases of proximal ureteral calculi. PMID:26617636

  18. Treatment of verb anomia in aphasia: efficacy of self-administered therapy using a smart tablet.

    PubMed

    Lavoie, Monica; Routhier, Sonia; Légaré, Annie; Macoir, Joël

    2016-01-01

    Aphasia is a chronic condition that usually requires long-term rehabilitation. However, even if many effective treatments can be offered to patients and families, speech therapy services for individuals with aphasia often remain limited because of logistical and financial considerations, especially more than 6 months after stroke. Therefore, the need to develop tools to maximize rehabilitation potential is unquestionable. The aim of this study was to test the efficacy of a self-administered treatment delivered with a smart tablet to improve written verb naming skills in CP, a 63-year-old woman with chronic aphasia. An ABA multiple baseline design was used to compare CP's performance in verb naming on three equivalent lists of stimuli trained with a hierarchy of cues, trained with no cues, and not trained. Results suggest that graphemic cueing therapy, done four times a week for 3 weeks, led to better written verb naming compared to baseline and to the untrained list. Moreover, generalization of the effects of treatment was observed in verb production, assessed with a noun-to-verb production task. Results of this study suggest that self-administered training with a smart tablet is effective in improving naming skills in chronic aphasia. Future studies are needed to confirm the effectiveness of new technologies in self-administered treatment of acquired language deficits.

  19. Flexible Ureteroscopy Can Be More Efficacious in the Treatment of Proximal Ureteral Stones in Select Patients.

    PubMed

    Alkan, Erdal; Sarıbacak, Ali; Ozkanli, Ahmet Oguz; Basar, Mehmet Murad; Acar, Oguz; Balbay, Mevlana Derya

    2015-01-01

    Purpose. We aimed to compare and evaluate the outcomes and complications of two endoscopic treatment procedures, semirigid ureteroscopy (SR-URS) and flexible ureteroscopy (F-URS), in the treatment of proximal ureteral stones (PUS). Methods. SR-URS (group 1) was done on 68 patients whereas 64 patients underwent F-URS (group 2) for the treatment of PUS. Success rate was defined as the absence of stone fragments or presence of asymptomatic insignificant residual fragments < 2 mm. Outcomes and complications were recorded. Results. The differences were statistically not significant in age, gender, body mass index (BMI), and stone characteristics between groups. Mean ureteral stone size was 9.1 ± 0.4 mm and 8.9 ± 0.5 mm for groups 1 and 2. Mean operative time was 34.1 ± 1.5 min and 49.4 ± 2.3 min for groups 1 and 2 (p = 0.001). SFRs were 76.5% and 87.5% for groups 1 and 2 (p = 0.078). Two major complications (ureteral avulsion and ureteral rupture) occurred in group 1. Conclusion. F-URS is safer and less invasive than SR-URS in patients with PUS. There is no statistically significant difference in the efficacy of either technique. Nonetheless we recommend F-URS in the management of PUS as a first-line treatment option in select cases of proximal ureteral calculi. PMID:26617636

  20. Perceived treatment efficacy for conventional and alternative therapies reported by persons with multiple chemical sensitivity.

    PubMed Central

    Gibson, Pamela Reed; Elms, Amy Nicole-Marie; Ruding, Lisa Ann

    2003-01-01

    Multiple chemical sensitivity (MCS) is a condition in which persons experience negative health effects in multiple organ systems from exposure to low levels of common chemicals. Although symptoms experienced from particular chemicals vary across persons, they are generally stable within persons. The sensitivities often spread over time, first to related chemicals and then to other classes of chemicals. This study examined self-reported perceived treatment efficacy of 101 treatments used by 917 persons with self-reported MCS. Treatments examined included environmental medicine techniques, holistic therapies, individual nutritional supplements, detoxification techniques, body therapies, Eastern-origin techniques, newer therapies, prescription items, and others. The three most highly rated treatments were creating a chemical-free living space, chemical avoidance, and prayer. Both creating a chemical-free living space and chemical avoidance were rated by 95% of respondents as helpful. Results for most therapies were mixed. Participants had consulted a mean of 12 health care providers and spent over one-third of their annual income on health care costs. We discuss this drain on personal resources and describe respondents' attitudes toward the possibility of healing from MCS. PMID:12948890

  1. Efficacy and safety of morniflumate for the treatment of symptoms associated with soft tissue inflammation.

    PubMed

    Cremonesi, Giovanni; Cavalieri, Luca

    2015-06-01

    The effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of pain in osteoarthritis and other musculoskeletal diseases is well documented. The role of NSAIDs is less clear in the treatment of conditions involving soft tissue inflammation, including the airways, ear-nose-throat (ENT) system and urogenital tract. These conditions are often treated inappropriately with antibiotics. Morniflumate, the ß-morpholinoethyl ester of niflumic acid, is a member of the fenamate family of NSAIDs indicated for the treatment of inflammatory conditions (with or without pain) affecting airways, the ENT system, urogenital tract and the osteoarticular system. Morniflumate has a 30-year history of clinical use, particularly for the treatment of pain associated with paediatric ENT infection. This article reviews evidence supporting the efficacy and safety of morniflumate. Based on available evidence and the favourable tolerability profile emerging from extensive clinical use, morniflumate appears to be a valid and well-tolerated alternative to other NSAIDs, or to antibiotics, for the treatment of pain and other symptoms of soft tissue inflammation.

  2. Sativex: clinical efficacy and tolerability in the treatment of symptoms of multiple sclerosis and neuropathic pain.

    PubMed

    Barnes, Michael Philip

    2006-04-01

    Sativex is one of the first cannabis-based medicines to undergo conventional clinical development and to be approved as a prescription medicine. It is an oromucosal spray that allows flexible, individualised dosing. Patients self titrate their overall dose and pattern of dosing according to their response to and tolerance of the medicine. This usually results in the administration of approximately 8-12 sprays/day. Each spray delivers tetrahydrocannabinol 2.7 mg and cannabidiol 2.5 mg, giving an approximate average dose of tetrahydrocannabinol 22-32 mg/day and cannabidiol 20-30 mg/day. Development has concentrated on the treatment of symptoms of multiple sclerosis, notably spasticity and neuropathic pain, as well as the treatment of neuropathic pain of other aetiologies. Positive results in placebo-controlled trials of the use of Sativex as an add-on therapy in these indications demonstrate that Sativex is efficacious and well tolerated in the treatment of these symptoms. Sativex has been approved for use in neuropathic pain due to multiple sclerosis in Canada. If ongoing studies replicate the results already observed, further approvals for the treatment of spasticity in multiple sclerosis and for neuropathic pain are likely. PMID:16553576

  3. Efficacy of prophylactic anti-diarrhoeal treatment in patients receiving Campto for advanced colorectal cancer.

    PubMed

    Duffour, J; Gourgou, S; Seitz, J F; Senesse, P; Boutet, O; Castera, D; Kramar, A; Ychou, M

    2002-01-01

    This study assessed the efficacy of combined prophylactic and curative anti-diarrhoeal medication in advanced colorectal patients treated by irinotecan. Thirty-four pre-treated eligible patients were evaluated. There were 44% women, the median age was 65 and 38% of the patients had a 0 performance status. The patients received sucralfate(4g/d) and nifuroxazide(600 mg/d) prophylactic treatment on days 0-7. In the case of severe diarrhoea, preventive treatment was replaced by loperamide(12 mg/d) and diosmectite (9 g/d). Grade 3 delayed diarrhoea occurred in 18% of patients (90% CI: [9.5-28.9]) and 4.6% of cycles. No grade 4 delayed diarrhoea was observed. Twenty-nine patients (85%) received the preventive treatment at cycle 1, while 14% (90% CI: [6.2-25.7]) experienced grade 3 delayed diarrhoea in 3.7% of cycles for a median 4.5 days. The objective response rate was 8% (90% CI [1.4-23.1]) among the 25 assessable patients. Preventive combined treatment is effective in reducing the incidence of severe delayed diarrhoea, and it should be proposed to patients treated with mono-therapy Campto(r) and evaluated in poly-chemotherapy protocols. PMID:12552984

  4. Clinical efficacy, safety, and tolerability of fingolimod for the treatment of relapsing-remitting multiple sclerosis

    PubMed Central

    Gajofatto, Alberto; Turatti, Marco; Monaco, Salvatore; Benedetti, Maria Donata

    2015-01-01

    Fingolimod is a selective immunosuppressive agent approved worldwide for the treatment of relapsing-remitting multiple sclerosis (MS), a chronic and potentially disabling neurological condition. Randomized double-blind clinical trials have shown that fingolimod significantly reduces relapse rate and ameliorates a number of brain MRI measures, including cerebral atrophy, compared to both placebo and intramuscular interferon-β1a. The effect on disability progression remains controversial, since one Phase III trial showed a significant benefit of treatment while two others did not. Although fingolimod has a very convenient daily oral dosing, the possibility of serious cardiac, ocular, infectious, and other rare adverse events justified the decision of the European Medicines Agency to approve the drug as a second-line treatment for MS patients not responsive to first-line therapy, or those with rapidly evolving course. In the United States, fingolimod is instead authorized as a first-line treatment. The aim of this review is to describe and discuss the characteristics of fingolimod concerning its efficacy, safety, and tolerability in the clinical context of multiple sclerosis management. PMID:26715860

  5. Critical appraisal of efficacy and safety of abatacept in the treatment of refractory rheumatoid arthritis

    PubMed Central

    Lundquist, Lisa M; Cole, Sabrina W; Augustine, Jill M

    2012-01-01

    Rheumatoid arthritis is a chronic, progressive, autoimmune disease that leads to significant disability and premature mortality. Various treatment options are available, but the foundation of treatment includes nonbiologic and biologic disease-modifying antirheumatic drugs. The incidence of patients with rheumatoid arthritis refractory to first-line agents is estimated to be at least 20%. Abatacept, a T cell costimulation modulator, is the first agent to interfere with full T cell activation by competing with CD28 for binding of CD80 and CD86, which results in decreased secretion of proinflammatory cytokines and autoantibody production. Current American College of Rheumatology treatment guidelines recommend abatacept for patients with at least moderate disease activity and a poor prognosis demonstrating an inadequate response to other agents. Several key Phase III trials have been conducted to evaluate the efficacy and safety of abatacept in patients with an inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy. Response rates in all trials showed statistically significant improvements compared with placebo according to American College of Rheumatology criteria for disease improvement. The most common adverse event report in patients receiving abatacept was infection; however, the frequency of adverse events was similar to placebo. Abatacept is a safe and effective rheumatoid arthritis treatment for patients with an inadequate response to methotrexate or anti-tumor necrosis factor alpha therapy.

  6. Clinical efficacy of Ayurveda treatment regimen on Subfertility with Poly Cystic Ovarian Syndrome (PCOS)

    PubMed Central

    Dayani Siriwardene, S. A.; Karunathilaka, L. P. A; Kodituwakku, N. D.; Karunarathne, Y. A. U. D.

    2010-01-01

    Poly Cystic Ovarian Syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, resulting from insulin resistance and the compensatory hyperinsulinemia. This results in adverse effect on multiple organ systems and may result in alteration in serum lipids, anovulation, abnormal uterine bleeding and infertility. According to Ayurvedic view PCOS can be correlated with Aarthava Kshaya. It was revealed that most of subfertility patients who were presented Osuki Ayurveda Centre suffered from the PCOS. Therefore the present study was carried out for the clinical evaluation of the efficacy of Ayurveda treatment regimen on subfertility with PCOS. Total 40 patients were selected by using purposive sampling method. According to the Ayurveda theories of Shodhana, Shamana and Tarpana, the treatment was conducted in 3 stages for the duration of 6 months. The response to the treatment was recorded and therapeutic effects were evaluated by symptomatic relief and through Trans Vaginal Scan and LH, FSH hormone levels. The results revealed that, subfertility due to PCOS can be cured successfully by using this Ayurveda treatment regimen. PMID:22131680

  7. Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring.

    PubMed

    Pollitt, Laura C; Sim, Derek; Salathé, Rahel; Read, Andrew F

    2015-03-01

    Artemisinin-based drugs are the front-line weapon in the treatment of human malaria cases, but there is concern that recent reports of slow clearing infections may signal developing resistance to treatment. In the absence of molecular markers for resistance, current efforts to monitor drug efficacy are based on the rate at which parasites are cleared from infections. However, some knowledge of the standing variation in parasite susceptibility is needed to identify a meaningful increase in infection half-life. Here, we show that five previously unexposed genotypes of the rodent malaria parasite Plasmodium chabaudi differ substantially in their in vivo response to treatment. Slower clearance rates were not linked to parasite virulence or growth rate, going against the suggestion that drug treatment will drive the evolution of virulence in this system. The level of variation observed here in a relatively small number of genotypes suggests existing 'resistant' parasites could be present in the population and therefore, increased parasite clearance rates could represent selection on pre-existing variation rather than de novo resistance events. This has implications for resistance monitoring as susceptibility may depend on evolved traits unrelated to drug exposure. PMID:25861387

  8. Clinical efficacy of the Er:YAG laser treatment on hypersensitive dentin.

    PubMed

    Yu, Chuan-Hang; Chang, Yu-Chao

    2014-06-01

    Dentin hypersensitivity is a common symptomatic condition that causes discomfort and sometimes severe pain. The purpose of this study was to evaluate the clinical efficacy of the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser treatment on cervically exposed hypersensitive dentin. Twenty patients with dentin hypersensitivity of caries-free teeth were selected. A visual analog scale (VAS) was used to measure dentin sensitivity in response to air stimulus. A 2-minute Er:YAG laser (energy level: 60 mJ/pulse; repetition rate: 2 Hz) was applied to cervically exposed hypersensitive dentin. After 4 weeks, the hypersensitive teeth were examined again, and the VAS score was measured again and recorded. No complications such as detrimental pulpal effects were observed. Eighteen participants reported significantly reduced dentin hypersensitivity 4 weeks after the laser desensitization treatment. The VAS scores measured 4 weeks after the Er:YAG laser desensitization treatment were significantly decreased as compared with those measured at the baseline (p < 0.05). In conclusion, the Er:YAG laser desensitization treatment can effectively reduce hypersensitivity of cervically exposed hypersensitive dentin. PMID:23602018

  9. Differential Control Efficacies of Vitamin Treatments against Bacterial Wilt and Grey Mould Diseases in Tomato Plants

    PubMed Central

    Hong, Jeum Kyu; Kim, Hyeon Ji; Jung, Heesoo; Yang, Hye Ji; Kim, Do Hoon; Sung, Chang Hyun; Park, Chang-Jin; Chang, Seog Won

    2016-01-01

    Bacterial wilt and grey mould in tomato plants are economically destructive bacterial and fungal diseases caused by Ralstonia solanacearum and Botrytis cinerea, respectively. Various approaches including chemical and biological controls have been attempted to arrest the tomato diseases so far. In this study, in vitro growths of bacterial R. solanacearum and fungal B. cinerea were evaluated using four different vitamins including thiamine (vitamin B1), niacin (vitamin B3), pyridoxine (vitamin B6), and menadione (vitamin K3). In planta efficacies of the four vitamin treatments on tomato protection against both diseases were also demonstrated. All four vitamins showed different in vitro antibacterial activities against R. solanacearum in dose-dependent manners. However, treatment with 2 mM thiamine was only effective in reducing bacterial wilt of detached tomato leaves without phytotoxicity under lower disease pressure (106 colony-forming unit [cfu]/ml). Treatment with the vitamins also differentially reduced in vitro conidial germination and mycelial growth of B. cinerea. The four vitamins slightly reduced the conidial germination, and thiamine, pyridoxine and menadione inhibited the mycelial growth of B. cinerea. Menadione began to drastically suppress the conidial germination and mycelial growth by 5 and 0.5 mM, respectively. Grey mould symptoms on the inoculated tomato leaves were significantly reduced by pyridoxine and menadione pretreatments one day prior to the fungal challenge inoculation. These findings suggest that disease-specific vitamin treatment will be integrated for eco-friendly management of tomato bacterial wilt and grey mould. PMID:27721697

  10. Understanding genetic variation in in vivo tolerance to artesunate: implications for treatment efficacy and resistance monitoring

    PubMed Central

    Pollitt, Laura C; Sim, Derek; Salathé, Rahel; Read, Andrew F

    2015-01-01

    Artemisinin-based drugs are the front-line weapon in the treatment of human malaria cases, but there is concern that recent reports of slow clearing infections may signal developing resistance to treatment. In the absence of molecular markers for resistance, current efforts to monitor drug efficacy are based on the rate at which parasites are cleared from infections. However, some knowledge of the standing variation in parasite susceptibility is needed to identify a meaningful increase in infection half-life. Here, we show that five previously unexposed genotypes of the rodent malaria parasite Plasmodium chabaudi differ substantially in their in vivo response to treatment. Slower clearance rates were not linked to parasite virulence or growth rate, going against the suggestion that drug treatment will drive the evolution of virulence in this system. The level of variation observed here in a relatively small number of genotypes suggests existing ‘resistant’ parasites could be present in the population and therefore, increased parasite clearance rates could represent selection on pre-existing variation rather than de novo resistance events. This has implications for resistance monitoring as susceptibility may depend on evolved traits unrelated to drug exposure. PMID:25861387

  11. Development and psychometric validation of the REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire: a common measure of plaque-type psoriasis severity and treatment efficacy for patients and clinicians

    PubMed Central

    Gilet, H; Roborel de Climens, A; Arnould, B; Bachelez, H; Bagot, M; Beaulieu, P; Joly, P; Jullien, D; Le Maître, M; Ortonne, JP; Paul, C; Thibout, E

    2015-01-01

    Background To date, there is no global consensus on the definition of the severity of psoriasis. The REFlective evaLuation of psoriasis Efficacy of Treatment and Severity (REFLETS) questionnaire has recently been developed to provide a better understanding of plaque-type psoriasis severity and treatment efficacy from both patient and clinician perspectives. Objective This study aimed to develop and psychometrically validate the new REFLETS questionnaire to evaluate patient and clinician perceptions of plaque-type psoriasis severity and treatment efficacy. Methods Two similar versions of the REFLETS questionnaire were developed following a rigorous methodology for clinicians and patients, referring to ‘the psoriasis of your patient' or to ‘your psoriasis’, respectively. An observational, longitudinal, multicentre study was conducted in France with 34 dermatologists and 430 mild to severe plaque-type psoriasis patients to finalize the questionnaire and evaluate its psychometric properties. Results Two dimensions were defined – severity and treatment efficacy – with three subdimensions within severity (impact of psoriasis, symptoms and disease course), and two individual items on joint pain. The questionnaire was well accepted by clinicians and patients. Excellent internal consistency (Cronbach's alpha = 0.66–0.98) and test–retest reliability (intraclass correlation coefficients = 0.83–0.94) were demonstrated. REFLETS scores were moderately to highly correlated to Psoriasis Area and Severity Index (r = 0.35–0.70), Skindex-29 (r = 0.46–0.82) and DLQI scores (r = 0.36–0.82). Patients with decreased psoriasis severity and those with increased treatment efficacy, according to patient global evaluations, had lower severity and higher treatment efficacy REFLETS scores, respectively. Conclusion REFlective evaLuation of psoriasis Efficacy of Treatment and Severity is a promising tool for assessing plaque-type psoriasis severity and treatment

  12. Efficacy of silodosin in the treatment of distal ureteral stones 4 to 10 mm in diameter

    PubMed Central

    Yuksel, Mustafa; Yilmaz, Serdar; Tokgoz, Husnu; Yalcinkaya, Soner; Baş, Serkan; Ipekci, Tümay; Yildiz, Ali; Ates, Nihat; Savas, Murat

    2015-01-01

    Purpose: Few studies have investigated the efficacy of silodosin, a recently introduced selective alpha 1-A adrenoceptor antagonist, in medical expulsive therapy (MET) for ureteral calculi. The results of these studies, which all evaluated the efficacy of 8 mg/day, indicate that silodosin is a potential treatment for ureteral calculi. This study investigated the efficacy of 4 mg/day of silodosin for MET of distal ureteral stones 4 to 10 mm in diameter. Material and Method: After 70 patients had been randomized into 2 groups of 35 patients each, both the control and experimental groups (groups 1 and 2, respectively) were advised to take 75 mg/day of diclofenacsodiumas needed for pain relief but only the experimental group to take 4 mg/day of silodosin. After 21 days, the groups were compared regarding the stone expulsion rate and duration, number of renalcolicepisodes, and analgesicdosage. Results: The median expulsion rates were 71.4% and 91.4% in groups 1 and 2, respectively, and the difference between them was significant (P=0.031). The median expulsion durations were 12.91±6.14 and 8.03±4.99 days, respectively, and the difference between them was significant (P<0.001). No significant differences were found regarding the median number of renal colic episodes or median analgesic dosage. While no patients in group 1 experienced side effects, 5 patients (14%) in group 2 experienced retrograde ejaculation. Conclusion: These results indicate that 4 mg/day of silodos in facilitates the expulsion of distal ureteral stones 4 to 10 mm in diameter but does not significantly reduce the number of renal colic episodes or analgesic dosage. PMID:26770537

  13. Efficacy, safety, and cost of surgical versus nonsurgical treatment for carpal tunnel syndrome

    PubMed Central

    Ren, Yi-Ming; Wang, Xi-Shan; Wei, Zhi-Jian; Fan, Bao-You; Lin, Wei; Zhou, Xian-Hu; Feng, Shi-Qing

    2016-01-01

    Abstract Background: Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disease. Either surgical or conservative intervention for CTS patients is needed to choose. We conducted this systematic review and meta-analysis to compare the clinical efficacy, safety, and cost of surgical versus nonsurgical intervention. Methods: The eligible studies were acquired from PubMed, Medline, Embase, Web of Science, Google, and Cochrane Library. The data were extracted by 2 of the coauthors independently and were analyzed by RevMan5.3. Standardized mean differences (SMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration Risk of Bias Tool and Newcastle–Ottawa Scale were used to assess risk of bias. Results: Thirteen studies including 9 randomized controlled trials (RCTs) and 4 observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The difference of clinical efficacy was statistically significant between surgical and nonsurgical intervention, and nonsurgical treatment was more effective (OR = 2.35, 95%CI = 1.18–4.67, P = 0.01). Meanwhile, different results were discovered by subgroup analysis. The pooled results of function improvement, symptom improvement, neurophysiological parameters improvement, and cost of care at different follow-up times showed that the differences were not statistically significant between the 2 interventions. The difference of complications and side-effects was statistically significant and conservative treatment achieved better result than surgery (OR = 2.03, 95%CI = 1.28–3.22, P = 0.003). Sensitivity analysis proved the stability of the pooled results. Conclusion: Both surgical and conservative interventions had benefits in CTS. Nonsurgical treatment was more effective and safety than surgical treatment, but there were no significant differences in function improvement, symptom improvement, neurophysiological

  14. Impact of Water Management on Efficacy of Insecticide Seed Treatments Against Rice Water Weevil (Coleoptera: Curculionidae) in Mississippi Rice

    PubMed Central

    Adams, A.; Gore, J.; Musser, F.; Cook, D.; Catchot, A.; Walker, T.; Awuni, G. A.

    2015-01-01

    Two experiments were conducted at the Delta Research and Extension Center in Stoneville, MS, during 2011 and 2012 to determine the impact of water management practices on the efficacy of insecticidal seed treatments targeting rice water weevil, Lissorhoptrus oryzophilus Kuschel. Larval densities and yield were compared for plots treated with labeled rates of thiamethoxam, chlorantraniliprole, and clothianidin and an untreated control. In the first experiment, plots were subjected to flood initiated at 6 and 8 wk after planting. Seed treatments significantly reduced larval densities with the 8-wk flood timing, but not the 6-wk flood timing. Overall, the treated plots yielded higher than the control plots. In the second experiment, the impact of multiple flushes on the efficacy of insecticidal seed treatments was evaluated. Plots were subjected to zero, one, or two flushes with water. All seed treatments reduced larval densities compared with the untreated control. Significantly fewer larvae were observed in plots that received one or two flushes compared with plots that did not receive a flush. All seed treatments resulted in higher yields compared to the untreated control in the zero and one flush treatments. When two flushes were applied, yield from the thiamethoxam and clothianidin treated plots was not significantly different from those of the control plots, while the chlorantraniliprole treated plots yielded significantly higher than the control. These data suggest that time from planting to flood did not impact the efficacy of seed treatments, but multiple flushes reduced the efficacy of thiamethoxam and clothianidin. PMID:26470232

  15. Impact of Water Management on Efficacy of Insecticide Seed Treatments Against Rice Water Weevil (Coleoptera: Curculionidae) in Mississippi Rice.

    PubMed

    Adams, A; Gore, J; Musser, F; Cook, D; Catchot, A; Walker, T; Awuni, G A

    2015-06-01

    Two experiments were conducted at the Delta Research and Extension Center in Stoneville, MS, during 2011 and 2012 to determine the impact of water management practices on the efficacy of insecticidal seed treatments targeting rice water weevil, Lissorhoptrus oryzophilus Kuschel. Larval densities and yield were compared for plots treated with labeled rates of thiamethoxam, chlorantraniliprole, and clothianidin and an untreated control. In the first experiment, plots were subjected to flood initiated at 6 and 8 wk after planting. Seed treatments significantly reduced larval densities with the 8-wk flood timing, but not the 6-wk flood timing. Overall, the treated plots yielded higher than the control plots. In the second experiment, the impact of multiple flushes on the efficacy of insecticidal seed treatments was evaluated. Plots were subjected to zero, one, or two flushes with water. All seed treatments reduced larval densities compared with the untreated control. Significantly fewer larvae were observed in plots that received one or two flushes compared with plots that did not receive a flush. All seed treatments resulted in higher yields compared to the untreated control in the zero and one flush treatments. When two flushes were applied, yield from the thiamethoxam and clothianidin treated plots was not significantly different from those of the control plots, while the chlorantraniliprole treated plots yielded significantly higher than the control. These data suggest that time from planting to flood did not impact the efficacy of seed treatments, but multiple flushes reduced the efficacy of thiamethoxam and clothianidin. PMID:26470232

  16. Efficacy of mebendazole and levamisole alone or in combination against intestinal nematode infections after repeated targeted mebendazole treatment in Zanzibar.

    PubMed Central

    Albonico, M.; Bickle, Q.; Ramsan, M.; Montresor, A.; Savioli, L.; Taylor, M.

    2003-01-01

    OBJECTIVE: To evaluate the efficacy of and resistance to mebendazole (500 mg) and levamisole (40 or 80 mg), alone or in combination, for the treatment of Ascaris lumbricoides, Trichuris trichiura and hookworm infections on Pemba Island - an area exposed to periodic school-based mebendazole treatment since 1994. METHODS: A randomized, placebo-controlled trial was carried out in 914 children enrolled from the first and fifth grades of primary schools. Stool samples collected at baseline and 21 days after treatment were examined by the Kato-Katz technique to assess the prevalence and intensity of helminth infection. FINDINGS: Efficacies of mebendazole and levamisole as single treatments against intestinal nematode infections were comparable with those in previous trials, but mebendazole treatment of hookworm infections gave significantly lower cure (7.6%) and egg reduction (52.1%) rates than reported in a study undertaken before the beginning of periodic chemotherapy (cure rate, 22.4%; egg reduction rate, 82.4%). Combined treatment with mebendazole and levamisole had a significantly higher efficacy against hookworm infections (cure rate, 26.1%; egg reduction rate, 88.7%) than either drug given alone. No difference in mebendazole efficacy was found in children who had been treated repeatedly compared with those who had not been treated previously. CONCLUSION: The overall efficacy of mebendazole against hookworm infections after periodic chemotherapy is reduced. The efficacy of benzimidazoles in chemotherapy-based control programmes should be monitored closely. Combined treatment with mebendazole and levamisole may be useful as a tool to delay the development of benzimidazole resistance. PMID:12856052

  17. [Efficacy of corneal cross-linking for the treatment of keratoconus].

    PubMed

    Touboul, D; Robinet-Perrin, A; Fournié, P; Malecaze, F

    2016-03-01

    Keratoconus (KC) is a complex disease whose pathophysiology is only partially understood. The priority in management is to halt the progression of corneal deformation as soon as possible in the course of KC disease. Corneal cross-linking (CXL) is at present the only dedicated treatment for this purpose. Its biochemical mechanism of action leads to changes in the viscoelastic properties of the cornea induced by matrix bonding and renewal of keratocytes. The effect of CXL is difficult to quantify when measured in in-vivo conditions because of a lack of consistent tools adapted for clinical practice. Nevertheless, a large amount of evidence has been collected so far confirming the positive action of CXL on corneal structural reinforcement, and numerous studies have demonstrated significant efficacy in halting progression of KC with long-term follow-up. Published studies, however, are of relatively low scientific power given the great heterogeneity of the disease and the numerous associated biases in evaluation. The purpose of this paper is to summarize the consistent evidence of efficacy of CXL and to justify its role in our therapeutic armamentarium for management of progressive KC. PMID:26995077

  18. Comparing two books and establishing probably efficacious treatment for low sexual desire.

    PubMed

    Balzer, Alexandra M; Mintz, Laurie B

    2015-04-01

    Using a sample of 45 women, this study compared the effectiveness of a previously studied (Mintz, Balzer, Zhao, & Bush, 2012) bibliotherapy intervention (Mintz, 2009), a similar self-help book (Hall, 2004), and a wait-list control (WLC) group. To examine intervention effectiveness, between and within group standardized effect sizes (interpreted with Cohen's, 1988 benchmarks .20 = small, .50 = medium, .80+ = large) and their confidence limits are used. In comparison to the WLC group, both interventions yielded large between-group posttest effect sizes on a measure of sexual desire. Additionally, large between-group posttest effect sizes were found for sexual satisfaction and lubrication among those reading the Mintz book. When examining within-group pretest to posttest effect sizes, medium to large effects were found for desire, lubrication, and orgasm for both books and for satisfaction and arousal for those reading the Mintz book. When directly comparing the books, all between-group posttest effect sizes were likely obtained by chance. It is concluded that both books are equally effective in terms of the outcome of desire, but whether or not there is differential efficacy in terms of other domains of sexual functioning is equivocal. Tentative evidence is provided for the longer term effectiveness of both books in enhancing desire. Arguing for applying criteria for empirically supported treatments to self-help, results are purported to establish the Mintz book as probably efficacious and to comprise a first step in this designation for the Hall book.

  19. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    PubMed

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy. PMID:20136435

  20. Safety and efficacy of travoprost solution for the treatment of elevated intraocular pressure

    PubMed Central

    Quaranta, Luciano; Riva, Ivano; Katsanos, Andreas; Floriani, Irene; Centofanti, Marco; Konstas, Anastasios G P

    2015-01-01

    Travoprost is a prostaglandin analogue widely used for reducing intraocular pressure (IOP) in patients affected with glaucoma and ocular hypertension. It exerts its ocular hypotensive effect through the prostaglandin FP receptors, located in the ciliary muscle and the trabecular meshwork. Several studies have shown that topical administration of travoprost induces a mean IOP reduction ranging from 25% to 32%, and sustained throughout the 24-hour cycle. When compared with timolol, travoprost is more effective at reducing IOP, while generally no difference has been found in the head-to-head comparison with other prostaglandin analogues. The fixed combination of travoprost and timolol has demonstrated a hypotensive efficacy comparable to the concomitant administration of the two drugs. Recently, a new preservative-free formulation of travoprost 0.004% has been marketed for reducing tolerability-related problems in subjects affected with ocular surface disease. Low rates of topical and systemic adverse reactions, strong ocular hypotensive efficacy, and once-a-day dosing make travoprost a first-line treatment for patients affected with elevated IOP. PMID:25914522

  1. Comparing two books and establishing probably efficacious treatment for low sexual desire.

    PubMed

    Balzer, Alexandra M; Mintz, Laurie B

    2015-04-01

    Using a sample of 45 women, this study compared the effectiveness of a previously studied (Mintz, Balzer, Zhao, & Bush, 2012) bibliotherapy intervention (Mintz, 2009), a similar self-help book (Hall, 2004), and a wait-list control (WLC) group. To examine intervention effectiveness, between and within group standardized effect sizes (interpreted with Cohen's, 1988 benchmarks .20 = small, .50 = medium, .80+ = large) and their confidence limits are used. In comparison to the WLC group, both interventions yielded large between-group posttest effect sizes on a measure of sexual desire. Additionally, large between-group posttest effect sizes were found for sexual satisfaction and lubrication among those reading the Mintz book. When examining within-group pretest to posttest effect sizes, medium to large effects were found for desire, lubrication, and orgasm for both books and for satisfaction and arousal for those reading the Mintz book. When directly comparing the books, all between-group posttest effect sizes were likely obtained by chance. It is concluded that both books are equally effective in terms of the outcome of desire, but whether or not there is differential efficacy in terms of other domains of sexual functioning is equivocal. Tentative evidence is provided for the longer term effectiveness of both books in enhancing desire. Arguing for applying criteria for empirically supported treatments to self-help, results are purported to establish the Mintz book as probably efficacious and to comprise a first step in this designation for the Hall book. PMID:25730171

  2. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

    PubMed

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P < .03). In the melanoma-bearing mice treated with IR, HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  3. A review on strontium ranelate long-term antifracture efficacy in the treatment of postmenopausal osteoporosis.

    PubMed

    Cianferotti, Luisella; D'Asta, Federica; Brandi, Maria Luisa

    2013-06-01

    Osteoporotic fractures are one of the major causes of increased morbidity and mortality in postmenopausal women and the overall aging population. One of the major issues in the management of postmenopausal osteoporosis is to find a safe and effective treatment in the long term (>3 years) to achieve and maintain a reduction in the risk of fracture. Strontium ranelate (PROTELOS(®)) is a relatively novel drug, currently approved in Europe for the treatment of postmenopausal osteoporosis. Strontium ranelate is the first agent of a new therapeutic class in osteoporosis, capable of both promoting bone formation and, to a lesser extent, inhibiting bone resorption. This uncoupling in bone turnover results in a net gain in bone mineral density (BMD), bone quality improvement and reduction in risk of vertebral and nonvertebral fractures, as initially demonstrated in the preplanned long-term registrative trials SOTI (Spinal Osteoporosis Therapeutic Intervention) and TROPOS (Treatment of Peripheral Osteoporosis) at 5 years. Recently, open-label extensions of the SOTI and TROPOS trials up to 8 and, recently, 10 years have confirmed the sustained efficacy of strontium ranelate in increasing BMD, the long-term safety profile and the high compliance to treatment, independently from baseline BMD or other risk factors for osteoporotic fractures. Recent economic impact analyses have proved that long-term treatment with strontium ranelate is highly cost effective, especially in women older than 70 years of age. Histomorphometric analyses in animals and humans participating in the phase III trials have proved that the quality of mineralization is preserved in the long term and bone microarchitecture is ameliorated, with increased bone strength. Thus, strontium ranelate has been confirmed to be an effective compound for the long-term, chronic treatment of postmenopausal osteoporosis. PMID:23858336

  4. Safety and efficacy of recombinant gamma interferon in the treatment of systemic sclerosis.

    PubMed Central

    Vlachoyiannopoulos, P G; Tsifetaki, N; Dimitriou, I; Galaris, D; Papiris, S A; Moutsopoulos, H M

    1996-01-01

    OBJECTIVE: To evaluate the safety and efficacy of recombinant gamma interferon (rIFN gamma) in the treatment of patients with systemic sclerosis. METHODS: Sixteen patients with systemic sclerosis were treated with r-IFN gamma, 60 micrograms m-2 (low dose, n = 10) and 150 micrograms m-2 (high dose, n = 6), three times weekly in an open phase I/II trial of eight months duration. The patients were stratified in low and high dose according to the severity and the extent of scleroderma; the two groups were comparable. RESULTS: The treatment was well tolerated. The most common side effects, almost certainly related to r-IFN gamma, were fever, chills, dizziness, headache, and severe flu-like syndrome with decreasing intensity with the time of treatment. Severe aphthous stomatitis (n = 1), ventricular tachycardia (n = 1), severe oesophageal ulcers due to gastro-oesophageal reflux (n = 1), disease exacerbation alone with frank arthritis and slight pericardial effusion (n = 1), and inability to conform to the requirements of the study (n = 1) were the reasons for discontinuing treatment. Side effects and degree of response were evident during the first five months of treatment. A significant decrease in mean skin thickness score was observed and was higher in the high dose group. Reactive oxygen species of peripheral neutrophils and soluble interleukin-2 receptor serum concentrations were higher than those of normal individuals at study entry and decreased in parallel with clinical improvement. CONCLUSIONS: Treatment of systemic sclerosis patients with r-IFN gamma was relatively safe and well tolerated for doses as high as 150 micrograms m-2 three times weekly. Side effects and the degree of response can be seen during the first months of therapy and can be used as predictors of ultimate toxicity or response. The drug seems to be effective in treating cutaneous scleroderma. PMID:8984943

  5. Efficacy and safety of continuous 4-year telbivudine treatment in patients with chronic hepatitis B

    PubMed Central

    Wang, Y; Thongsawat, S; Gane, E J; Liaw, Y-F; Jia, J; Hou, J; Chan, H L Y; Papatheodoridis, G; Wan, M; Niu, J; Bao, W; Trylesinski, A; Naoumov, N V

    2013-01-01

    In the phase-III GLOBE/015 studies, telbivudine demonstrated superior efficacy vs lamivudine during 2-year treatment in HBeAg-positive and HBeAg-negative chronic hepatitis B (CHB). After completion, 847 patients had an option to continue telbivudine treatment for further 2 years. A total of 596 (70%) of telbivudine-treated patients, who were serum HBV DNA positive or negative and without genotypic resistance to telbivudine at the end of the GLOBE/015 trials, were enrolled into a further 2-year extension study. A group of 502 patients completed 4 years of continuous telbivudine treatment and were included in the telbivudine per-protocol population. Amongst 293 HBeAg-positive patients, 76.2% had undetectable serum HBV DNA and 86.0% had normal serum ALT at the end of 4 years. Notably, the cumulative rate of HBeAg seroconversion was 53.2%. Amongst 209 HBeAg-negative patients, 86.4% had undetectable HBV DNA and 89.6% had normal serum ALT. In patients who had discontinued telbivudine treatment due to HBeAg seroconversion, the HBeAg response was durable in 82% of patients (median 111 weeks of off-treatment follow-up). The cumulative 4-year resistance rate was 10.6% for HBeAg-positive and 10.0% for HBeAg-negative patients. Most adverse events were mild or moderate in severity and transient. Renal function measured by estimated glomerular filtration rate (eGFR) increased by 14.9 mL/min/1.73 m2 (16.6%) from baseline to 4 years (P < 0.0001). In conclusion, in HBeAg-positive and HBeAg-negative CHB patients without resistance after 2 years, two additional years of telbivudine treatment continued to provide effective viral suppression with a favourable safety profile. Moreover, telbivudine achieved 53% of HBeAg seroconversion in HBeAg-positive patients. PMID:23490388

  6. Improving Treatment Adherence in Bipolar Disorder: A Review of Current Psychosocial Treatment Efficacy and Recommendations for Future Treatment Development

    ERIC Educational Resources Information Center

    Gaudiano, Brandon A.; Weinstock, Lauren M.; Miller, Ivan W.

    2008-01-01

    Treatment adherence is a frequent problem in bipolar disorder, with research showing that more than 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at…

  7. Ethnic identity, spirituality, and self-efficacy influences on treatment outcomes among Hispanic American methadone maintenance clients.

    PubMed

    Wong, Eunice C; Longshore, Douglas

    2008-01-01

    There is increasing concern over whether standard health care services, such as substance abuse treatment, adequately account for important cultural influences, yet studies focusing on the impact of cultural influences on substance abuse treatment continue to be limited. The current study prospectively examined the effects of two cultural factors (ethnic identity and spirituality) on substance abuse treatment outcomes among Hispanic American clients (N=114) enrolled in methadone maintenance treatment. In addition, this study examined whether a commonly studied treatment factor (i.e., self-efficacy) significantly influenced treatment outcomes. Higher levels of self-efficacy at intake were related to increased odds of reported heroin abstinence and a lower number of drugs used at 1-year follow-up. Greater levels of ethnic identity were related to a greater number of drugs used at follow-up. No significant effects were found for spirituality.

  8. A passive acoustic device for real-time monitoring of the efficacy of shockwave lithotripsy treatment.

    PubMed

    Leighton, T G; Fedele, F; Coleman, A J; McCarthy, C; Ryves, S; Hurrell, A M; De Stefano, A; White, P R

    2008-10-01

    Extracorporeal shockwave lithotripsy (ESWL) is the preferred modality for the treatment of renal and ureteric stone disease. Currently X-ray or ultrasound B-scan imaging are used to locate the stone and to check that it remains targeted at the focus of the lithotripter during treatment. Neither imaging modality is particularly effective in allowing the efficacy of treatment to be judged during the treatment session. A new device is described that, when placed on the patient's skin, can passively monitor the acoustic signals that propagate through the body after each lithotripter shock, and which can provide useful information on the effectiveness of targeting. These acoustic time histories are analyzed in real time to extract the two main characteristic peak amplitudes (m(1) and m(2)) and the time between these peaks (t(c)). A set of rules based on the acoustic parameters was developed during a clinical study in which a complete set of acoustic and clinical data was obtained for 30 of the 118 subjects recruited. The rules, which complied with earlier computational fluid dynamics (CFD) modeling and in vitro tests, allow each shock to be classified as "effective" or "ineffective." These clinically-derived rules were then applied in a second clinical study in which complete datasets were obtained for 49 of the 85 subjects recruited. This second clinical study demonstrated almost perfect agreement (kappa = 0.94) between the number of successful treatments, defined as >50% fragmentation as determined by X-ray at the follow-up appointment, and a device-derived global treatment score, TS(0), a figure derived from the total number of effective shocks in any treatment. The acoustic system is shown to provide a test of the success of the treatment that has a sensitivity of 91.7% and a specificity of 100%. In addition to the predictive capability, the device provides valuable real-time feedback to the lithotripter operator by indicating the effectiveness of each shock, plus

  9. Efficacy of peroral endoscopic myotomy vs other achalasia treatments in improving esophageal function

    PubMed Central

    Sanaka, Madhusudhan R; Hayat, Umar; Thota, Prashanthi N; Jegadeesan, Ramprasad; Ray, Monica; Gabbard, Scott L; Wadhwa, Neha; Lopez, Rocio; Baker, Mark E; Murthy, Sudish; Raja, Siva

    2016-01-01

    Hg vs 6.6 mmHg respectively, P < 0.001). However, when the efficacy of three treatments were compared to each other in terms of improvement in TBE or HREM parameters at 2 mo, there was no significant difference (P > 0.05). CONCLUSION: POEM, PD and LHM were all effective in improving esophageal function in achalasia at short-term. There was no difference in efficacy between the three treatments. PMID:27239118

  10. Dietary treatments for childhood constipation: efficacy of dietary fiber and whole grains.

    PubMed

    Stewart, Maria L; Schroeder, Natalia M

    2013-02-01

    Constipation in children is defined on the basis of several clusters of symptoms, and these symptoms are likely to persist into adulthood. The aim of this review article is to summarize the current literature on the use of dietary fiber and whole grains as treatments for childhood constipation. Current recommendations for fiber intake in children vary substantially among organizations, suggesting that the function of fiber in children is not fully understood. Additionally, no formal definition of "whole grain" exists, which further complicates the interpretation of the literature. Few randomized controlled trials have examined the effect of dietary fiber supplementation in children with constipation. Currently, no randomized controlled trials have investigated the efficacy of whole grains in treating childhood constipation. This is an area that warrants further attention. Increasing the intake of dietary fiber and/or whole grain has the potential to relieve childhood constipation; however, additional randomized controlled trials are necessary to make a formal recommendation.

  11. Efficacy and safety of loratadine suspension in the treatment of children with allergic rhinitis.

    PubMed

    Boner, A L; Miglioranzi, P; Richelli, C; Marchesi, E; Andreoli, A

    1989-08-01

    The safety and efficacy of loratadine was compared with that of dexchlorpheniramine in children with allergic rhinitis. Twenty-one children received loratadine 0.11-0.24 mg/kg ideal body weight once daily and 19 dexchlorpheniramine 0.10-0.23 mg/kg every 8 h (0.30-0.69 mg/24 h) for 14 consecutive days. Both loratadine and dexchlorpheniramine were effective in reducing nasal and ocular symptoms in allergic children. Substantial improvement in allergy symptoms was observed at the first evaluation (day 3 of treatment) and was maintained for the study duration. No significant trend of abnormality in laboratory parameters was observed. Drowsiness was present only in the dexchlorpheniramine-treated group. Loratadine appears to be a simple, effective and safe therapy for seasonal allergic rhinitis.

  12. Efficacy of Tigecycline for Secondary Acinetobacter Bacteremia and Factors Associated with Treatment Failure

    PubMed Central

    Liou, Bo-Huang; Lee, Yi-Tzu; Liu, Po-Yu; Fung, Chang-Phone

    2015-01-01

    We describe the clinical outcome of 17 patients with secondary Acinetobacter bacteremia whose isolates had a tigecycline MIC of ≤2 mg/liter and who received tigecycline within 2 days of bacteremia onset. The 14-day mortality rate of the tigecycline cohort was 41.2% (7/17), which was significantly higher than that of those receiving other appropriate antimicrobial agents (13.8%, 9/65; P = 0.018). However, the percentages of end-stage renal disease and congestive heart failure were higher in the tigecycline cohort. The efficacy of tigecycline was contingent upon the illness severity and bacterial species. Tigecycline should be applied cautiously for treatment of Acinetobacter bacteremia. PMID:25824230

  13. Dyslipidemia: evidence of efficacy of the pharmacological and non-pharmacological treatment in the elderly

    PubMed Central

    Gravina, Claudia F; Bertolami, Marcelo; Rodrigues, Giselle HP

    2012-01-01

    The clinical decision to control risk factors for cardiovascular disease (CVD) in the elderly takes the followings into consideration: (1) the elderly life expectancy; (2) the elderly biological age and functional capacity; (3) the role of cardiovascular disease in the elderly group; (4) the prevalence of risk factors in the elderly; and (5) The effectiveness of treatment of risk factors in the elderly. A large number of studies showed the efficacy of secondary and primary prevention of dyslipidemia in the elderly. However, the only trial that included patients over 80 years was the Heart Protection Study (HPS). Statins are considered the first line therapy for lowering low-density lipoprotein cholesterol (LDL-C). Because lifestyle changes are very difficult to achieve, doctors in general tend to prescribe many drugs to control cardiovascular risk factors. However, healthy food consumption remains a cornerstone in primary and secondary cardiovascular prevention and should be implemented by everyone. PMID:22916052

  14. Balancing treatment efficacy, toxicity and complication risk in elderly patients with metastatic renal cell carcinoma.

    PubMed

    van den Brom, R R H; van Es, S C; Leliveld, A M; Gietema, J A; Hospers, G A P; de Jong, I J; de Vries, E G E; Oosting, S F

    2016-05-01

    The number of elderly patients with renal cell carcinoma is rising. Elderly patients differ from their younger counterparts in, among others, higher incidence of comorbidity and reduced organ function. Age influences outcome of surgery, and therefore has to be taken into account in elderly patients eligible for cytoreductive nephrectomy. Over the last decade several novel effective drugs have become available for the metastatic setting targeting angiogenesis and mammalian target of rapamycin. Immune checkpoint blockade with a programmed death 1 antibody has recently been shown to increase survival and further studies with immune checkpoint inhibitors are ongoing. In this review we summarize the available data on efficacy and toxicity of existing and emerging therapies for metastatic renal cell carcinoma in the elderly. Where possible, we provide evidence-based recommendations for treatment choices in elderly. PMID:27123882

  15. Neuroprotective, antimicrobial, antioxidant, chemotherapeutic, and antidiabetic properties of Salvia Reuterana: A mini review

    PubMed Central

    Jafari, Elham; Andalib, Sasan; Abed, Alireza; Rafieian-Kopaei, Mahmoud; Vaseghi, Golnaz

    2015-01-01

    Objectives: Herbal medicine is known as a valid alternative treatment. Salvia Reuterana, which has been used in the Iranian traditional medicine, is mostly distributed in the central highlands of Iran. Salvia Reuterana is a medicinal herb with various therapeutic usages. The aim of the present review is to take account of pharmacological properties of Salvia Reuterana. Materials and Methods: The present review summarizes the literature with respect to various pharmacological properties of Salvia Reuterana. Results: Salvia Reuterana possesses neurological, antimicrobial, antioxidant, chemotherapeutic, and antidiabetic properties. Conclusions: Salvia Reuterana can be used as an alternative for treatment of several disorders. PMID:25767752

  16. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer - 90Y conjugates in treatment of prostate tumors

    PubMed Central

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction The treatment of prostate cancer using a radiotherapeutic 90Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA)copolymer can be enhanced with localized tumor hyperthermia. An 111In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90Y HPMA copolymer with hyperthermia. Methods HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111In for imaging or 90Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors. PMID:24461626

  17. An update on the efficacy of psychological therapies in the treatment of obsessive-compulsive disorder in adults.

    PubMed

    Ponniah, Kathryn; Magiati, Iliana; Hollon, Steven D

    2013-04-01

    We conducted a review to provide an update on the efficacy of psychological treatments for OCD in general and with regard to specific symptom presentations. The PubMed and PsycINFO databases were searched for randomized controlled trials (RCTs) published up to mid February 2012. Forty-five such studies were identified. Exposure and response prevention (ERP) and cognitive-behavioral therapy (CBT) were found to be efficacious and specific for OCD. More purely cognitive interventions that did not include ERP or behavioral experiments were found to be possibly efficacious, as were Acceptance and Commitment Therapy, Motivational Interviewing as an adjunct to the established treatments, Eye Movement Desensitization and Reprocessing, and Satiation Therapy. There was little support for Stress Management or Psychodynamic Therapy. Although the majority of the studies recruited mixed or unspecified samples of patients and did not test for moderation, CBT was efficacious for obsessional patients who lacked overt rituals. One more purely cognitive intervention named Danger Ideation Reduction Therapy was found to be possibly efficacious for patients with contamination obsessions and washing compulsions. Although ERP and CBT are the best established psychological treatments for OCD, further research is needed to help elucidate which treatments are most effective for different OCD presentations. PMID:23888284

  18. An Updated Meta-Analysis of the Efficacy and Safety of Acupuncture Treatment for Cerebral Infarction

    PubMed Central

    Li, Li; Zhang, Hong; Meng, Shu-qing; Qian, Hai-zhou

    2014-01-01

    Background Ischemic stroke is the second most common cause of death and the primary cause of disability throughout the world. Acupuncture is frequently advocated as an adjunct treatment during stroke rehabilitation. The aim of this study was to update the clinical efficacy and safety of acupuncture for cerebral infarction. Methods Randomized controlled trials (RCT) on acupuncture treating cerebral infarction were searched from the following databases: PubMed, EMBASE, Cochrane Library, CNKI, CMB and VIP from inception to October 2013. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods. The meta-analyses were conducted using Rev Man 5.0 software. Results A total of 25 trials involving 2224 patients were included. The results of this meta-analysis showed that the groups receiving acupuncture (observation group) were superior to the comparison groups (control group), with significant differences in the Clinical Efficacy Rates [OR = 4.04, 95%CI (2.93, 5.57), P<0.001], Fugl-Meyer Assessment [MD = 11.22, 95%CI (7.62, 14.82), P<0.001], Barthel Index Score [MD = 12.84, 95%CI (9.85, 15.82), P<0.001], and Neurological Deficit Score [MD = −2.71, 95% CI (−3.84, −1.94), P<0.001]. Three trials reported minor adverse events. Conclusion Current evidence provisionally demonstrates that acupuncture treatment is superior to either non-acupuncture or conventional therapy for cerebral infarction. Despite this conclusion, given the often low quality of the available trials, further large scale RCTs of better quality are still needed. PMID:25438041

  19. [Efficacy of somatostatin and its analogues in the treatment of acute pancreatitis: clinical retrospective study].

    PubMed

    Citone, G; Perri, S; Nardi, M; Maira, E; Lotti, R; Gabbrielli, F; Antonellis, M; Orsini, S

    2001-04-01

    Acute pancreatitis is an acute inflammatory disease of the pancreas, with variable involvement of other regional tissues or remote organ systems. Acute pancreatitis is mild in 80% of cases; virtually all patients with this form of disease will survive, because it's associated with minimal organ dysfunction and uneventful recovery; the severe pancreatitis develops in 20% of cases and is associated with higher morbidity and mortality. It's most important to identify the severity of disease at the moment of hospital admission; many scoring systems have been developed to serve as early prognostic signs: Ranson's criteria, Imrie's criteria, Apache II score, Balthazar's TC score. Recently, new drugs have been proposed in the treatment of acute pancreatitis, as, for example, calcitonine, glucagon, systemic antioxidants, antagonists of the receptors of interleukines, antiproteases (aprotinin and gabexate-mesilate) and the inhibitors of pancreatic secretions (somatostatin and its analogues). However, many controversies still exist concerning the real efficacy of these drugs in the treatment of acute pancreatitis, particularly regarding the inhibitors of pancreatic secretions: recently, some studies showed that somatostatin is able to actually reduce the local complication of the disease and the development of severe forms of acute pancreatitis; on the other hand, other studies failed to show real advantages of somatostatin reducing morbidity and mortality for pancreatitis. The aim of present study is a retrospective analysis of patients affected by acute pancreatitis in order to evaluate efficacy of somatostatin and its analogues. All patients subdivided in two groups: group A, patients treated with conventional therapy plus somatostatin and/or octreotide (SS/LS), and group B, patients treated only with conventional therapy. Results seem to show that somatostatin does not positively affect morbidity and mortality in patients with acute pancreatitis. The Authors conclude

  20. Efficacy of Aliskiren/Hydrochlorothiazide Combination for the Treatment of Hypertension: A Meta-Analytical Approach

    PubMed Central

    Morgado, Manuel P; Rolo, Sandra A; Castelo-Branco, Miguel

    2011-01-01

    Background: Single-pill combinations of aliskiren/hydrochlorothiazide have recently been approved by the European Medicines Agency for the treatment of hypertension. Objective: This study aimed to assess the antihypertensive efficacy of aliskiren/hydrochlorothiazide combination in reducing systolic and diastolic blood pressure in hypertensive patients. Methods: A search in International Pharmaceutical Abstracts, MEDLINE, The Cochrane Library and ISI Web of Knowledge was performed from 2000 to November 2009, to identify randomized, double-blind, clinical trials using aliskiren/hydrochlorothiazide for the treatment of hypertension. Studies were included if they evaluated the antihypertensive efficacy of aliskiren/hydrochlorothiazide in patients with mild or moderate essential hypertension and age ≥ 18 years. The meta-analytical approach calculated the weighted average reductions of systolic and diastolic blood pressure for each daily dosage combination. Results: We included 5 clinical trials testing several combinations of aliskiren/hydrochlorothiazide and containing data on 5448 patients. In all studies blood pressure was assessed at inclusion (baseline) and after 8 weeks of therapy. Blood pressure reductions and control rates were significantly (p < 0.05) higher with the aliskiren/hydrochlorothiazide combinations than with placebo and the same doses of aliskiren or hydrochlorothiazide alone. The weighted mean reductions (mm Hg) from baseline of systolic and diastolic blood pressure for each aliskiren/hydrochlorothiazide combination were: -15.8/-10.3 (150/25 mg); -15.9/-11.8 (300/12.5 mg); -16.9/-11.6 (300/25 mg). Blood pressure control rates (%) for the above combinations were, at least, respectively: 43.8, 50.1 and 51.9. Conclusions: Aliskiren/hydrochlorothiazide provided clinically significant additional blood pressure reductions and improved blood pressure control rates over aliskiren or hydrochlorothiazide monotherapy. PMID:21660247

  1. Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial.

    PubMed Central

    Ferrari, M. L. A.; Coelho, P. M. Z.; Antunes, C. M. F.; Tavares, C. A. P.; da Cunha, A. S.

    2003-01-01

    OBJECTIVE: To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection. METHODS: In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments. FINDINGS: The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%. CONCLUSIONS: Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides. PMID:12764515

  2. Virucidal efficacy of treatment with photodynamically activated curcumin on murine norovirus bio-accumulated in oysters.

    PubMed

    Wu, Juan; Hou, Wei; Cao, Binbin; Zuo, Tao; Xue, Changhu; Leung, Albert Wingnang; Xu, Chuanshan; Tang, Qing-Juan

    2015-09-01

    Norovirus (NoV) is one of the most important seafood- and water-borne viruses, and is a major cause of acute gastroenteritis outbreaks. In the present study we investigated the effect of curcumin as a sensitizer to photodynamic treatment both in buffer and in oysters against murine norovirus 1 (MNV-1), a surrogate of NoV. MNV-1 cultured in buffer and MNV-1 bio-accumulated in oysters were irradiated with a novel LED light source with a wavelength of 470nm and an energy of 3.6J/cm(2). Inactivation of MNV-1 was investigated by plaque assays. After virus was extracted from the gut of oysters treated over a range of curcumin concentrations, the ultrastructural morphology of the virus was observed using electron microscopy, and the integrity of viral nucleic acids and stability of viral capsid proteins were also determined. Results showed that the infectivity of MNV-1 was significantly inhibited by 1-3logPFU/ml, with significant damage to viral nucleic acids in a curcumin dose-dependent manner after photodynamic activation. Virus morphology was altered after the photodynamic treatment with curcumin, presumably due to the change of the viral capsid protein structures. The data suggest that treatment of oysters with photodynamic activation of curcumin is a potentially efficacious and cost-effective method to inactivate food-borne NoV. Further studies are necessary to evaluate the toxicology of this approach in detail and perform sensory evaluation of the treated product.

  3. The efficacy of physiotherapy for the prevention and treatment of prenatal symptoms: a systematic review.

    PubMed

    Van Kampen, Marijke; Devoogdt, Nele; De Groef, An; Gielen, Annelies; Geraerts, Inge

    2015-11-01

    Several studies have described the evidence of prenatal physiotherapy for one symptom, but none has made an overview. We provided a systematic review on the effectiveness of prenatal physiotherapy. A full search was conducted in three electronic databases (Embase, PubMed/MEDLINE and PEDro), selecting randomized controlled trials concerning prenatal physiotherapy. Methodological quality was assessed using the PEDro scale. We identified 1,249 studies and after exclusions 54 studies were included concerning the evidence of prenatal physiotherapy. The majority of studies indicated a preventative effect for low back pain/pelvic girdle pain, weight gain, incontinence, and perineal massage. For leg edema, fear, and prenatal depression, the efficacy was only based on one study per symptom. No preventative effect was found for gestational diabetes, while literature concerning gestational hypertensive disorders was inconclusive. Regarding the treatment of low back pain/pelvic girdle pain and weight gain, most therapies reduced pain and weight respectively. Evidence regarding exercises for diabetes was contradictory and only minimally researched for incontinence. Foot massage and stockings reduced leg edema and leg symptoms respectively. Concerning gestational hypertensive disorders, perineal pain, fear, and prenatal depression no treatment studies were performed. The majority of studies indicated that prenatal physiotherapy played a preventative role for low back pain/pelvic girdle pain, weight gain, incontinence, and pelvic pain. Evidence for the remaining symptoms was inclusive or only minimally investigated. Regarding treatment, most studies indicated a reduction of low back pain/pelvic girdle pain, weight gain, incontinence, and the symptoms of leg edema.

  4. The efficacy of permethrin 5% vs. oral ivermectin for the treatment of scabies.

    PubMed

    Ranjkesh, Mohammad Reza; Naghili, Behrouz; Goldust, Mohamad; Rezaee, Elham

    2013-01-01

    Human scabies is caused by an infestation of the skin by the human itch mite (Sarcoptes scabiei var. hominis). The aim of this study is to compare the efficacy and safety of permethrin 5% lotion with oral ivermectin for the treatment of scabies. In total, 60 patients with scabies were enrolled, and randomized into two groups: The first group and their family contacts received 5% permethrin cream twice with a one week interval, and the other received a single dose of oral ivermectin. Treatment was evaluated at intervals of 2 and 4 weeks. A single dose of ivermectin provided a cure rate of 62.4%, which increased to 92.8% with 2 doses at a 2-week interval. Treatment with two applications of permethrin with a one week interval was effective in 96.9% of patients. Permethrin-treated patients recovered earlier. Two applications of permethrin with a one week interval is more effective than a single dose of ivermectin. Two doses of ivermectin is as effective as a single application of permethrin.

  5. Safety and Efficacy of Micro-focused Ultrasound Plus Visualization for the Treatment of Axillary Hyperhidrosis

    PubMed Central

    Park, Hyunhee

    2014-01-01

    Objectives: To evaluate the safety, efficacy, and durability of treating axillary hyperhidrosis with high-intensity micro-focused ultrasound plus visualization. Design: Two randomized double-blind, sham-controlled pilot studies. Measurements: For Study 1, the primary endpoint was response defined as ≥50-percent reduction in baseline sweat production as measured gravimetrically. For Study 2, the primary endpoint was response defined as a reduction of Hyperhidrosis Disease Severity Scale scores from 3 or 4 to 1 or 2. Secondary endpoints included changes in gravimetric and starch-iodine testing and patient satisfaction. Results: In Study 1, ≥50 percent of patients achieved a positive treatment response. In Study 2, the response rate at post-treatment Day 60 for micro-focused ultrasound plus visualization- (N=12) and sham-treated (N=8) patients was 67 and zero percent, respectively (p=0.005). Patients evaluated 12 months after treatment (N=11) demonstrated the long-lasting effectiveness of micro-focused ultrasound plus visualization for treating axillary hyperhidrosis. All but one patient in the micro-focused ultrasound plus visualization group were satisfied with their results while all sham group patients were dissatisfied (p=0.0001). Subjective reports of greatest improvement were sweat production (92%) and social embarrassment (83%). Adverse events were found to be mild and were resolved within a short timeframe. Conclusion: Micro-focused ultrasound plus visualization appears to be safe, effective, well-tolerated, and a long-lasting means for treating axillary hyperhidrosis. PMID:24765226

  6. Clinical Efficacy in the Treatment of Overactive Bladder Refractory to Anticholinergics by Posterior Tibial Nerve Stimulation

    PubMed Central

    Palao-Yago, Francisco; Campon-Pacheco, Iluminada; Martinez-Sanchez, Maribel; Zuluaga-Gomez, Armando; Arrabal-Martin, Miguel

    2012-01-01

    Purpose Overactive bladder (OAB) is a clinical syndrome that is currently treated initially with anticholinergics, although some other therapeutic alternatives exist, such as neuromodulation, botulinum toxin, and posterior tibial nerve stimulation (PTNS). The purpose of this study was to assess the efficacy of PTNS in patients with OAB refractory to anticholinergics. Materials and Methods We present a cohort study of 14 women with OAB to whom we applied PTNS. We assessed (before and after the treatment) the diurnal micturitional frequency, the nocturnal micturitional frequency, urgency episodes, and urge incontinence episodes. Results were analyzed by using the Wilcoxon test for nonparametric samples. Results We observed statistically significant improvement in the diurnal micturitional frequency (p=0.05), in episodes of micturitional urgency (p=0.03), and in episodes of urge incontinence (p=0.004). A total of 50% of the patients felt subjective improvement from their pathology. Conclusions PTNS is a valid, minimally invasive treatment option with minimum morbidity for patients with OAB refractory to treatment with anticholinergics. PMID:22866220

  7. Comparison of efficacy of alternative medicine with allopathy in treatment of oral fungal infection.

    PubMed

    Maghu, Sahil; Desai, Vela D; Sharma, Rajeev

    2016-01-01

    This clinical study assessed and compared the efficacy of tea tree oil (TTO), an alternative form of medicine, with clotrimazole (i.e., allopathy) and a conservative form of management in the treatment of oral fungal infection. In this interventional, observational, and comparative study, we enrolled 36 medically fit individuals of both sexes who were aged 20-60 years old. The participants were randomly assigned to three groups. Group I was given TTO (0.25% rinse) as medicament, Group II was given clotrimazole, and Group III was managed with conservative treatment. The results were analyzed from the clinical evaluation of lesions, changes in four most common clinical parameters of lesions, and subjective symptoms on periodic follow-up. Based on the results, the percentage efficiency of the two groups were taken and compared through a bar graph on the scale of 1. No toxicity to TTO was reported. Group I (TTO) was found to be more efficient than the other two groups, as changes in four parameter indices of lesions were noted, and results for all three groups were compared on a percentage basis. The study concluded that TTO, being a natural product, is a better nontoxic modality compared to clotrimazole, in the treatment of oral fungal infection and has a promising future for its potential application in oral health products. PMID:26870682

  8. Comparative efficacy and safety of trimebutine versus mebeverine in the treatment of irritable bowel syndrome.

    PubMed

    Rahman, M Z; Ahmed, D S; Mahmuduzzaman, M; Rahman, M A; Chowdhury, M S; Barua, R; Ishaque, S M

    2014-01-01

    Irritable bowel syndrome (IBS) is a functional disorder characterized by chronic or recurrent abdominal pain or discomfort with bowel disturbances. This prospective, randomized clinical trial has been conducted on IBS patients, using trimebutine and Mebeverine in separate group in parallel design to compare the efficacy and safety of Trimebutine 100mg twice daily with mebeverine 135mg twice daily. Patients of 15 to 60 years old and both sexes were included from the out patient department (OPD) of gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU) from June 2010 to December 2011. A validated IBS-QOL instrument consisted of 34 questions used to assess improvement of quality of life before and after treatment. A total of 140 patients were enrolled in this study. Eighteen patients dropped out. One hundred twenty two patients completed the trial. In this study at the end of 6 weeks therapy, improvement of symptoms was statistically significant. However, differences of improvement between the two groups in relieving various symptoms were not statistically significant. Mean QOL score before treatment was 103 in Trimebutine group and 106 in Mebeverine group. After 6 weeks of treatment mean QOL score was 82 in Trimebutine group and 95 in Mebeverine group indicating improvement in both groups was statistically significant. The difference between the two groups was also significant. No worsening of symptoms and no side effects of the therapeutic agents was observed in any patient during the trial. PMID:24584382

  9. Efficacy of parecoxib, sumatriptan, and rizatriptan in the treatment of acute migraine attacks.

    PubMed

    Müller, Thomas; Lohse, Lutz

    2011-01-01

    Triptans and analgetic nonsteroidal inflammatory drugs reduce acute pain syndromes in migraine. A further treatment option for an acute headache attack in patients with migraine may be the application of cyclooxygenase-2-specific inhibitors, as they have anti-inflammatory and analgesic properties. The objective of this pilot study was to investigate the effects of an oral fast-dissolving tablet of 10 mg of rizatriptan, an intravenous infusion of 40 mg of parecoxib, and a subcutaneous pen injection of sumatriptan (6 mg/0.5 mL) on pain relief in 3 cohorts of patients with episodic migraine. They were treated owing to the acute onset of a pain attack as a case of emergency. They were randomized to treatment with sumatriptan, rizatriptan, or parecoxib. The participants completed a visual analog scale for pain intensity at baseline before the drug administration and then after intervals of 20, 30, 60, and 120 minutes. Rizatriptan, parecoxib, and sumatriptan reduced pain symptoms. Twenty and 30 minutes after drug intake, rizatriptan was more efficacious than parecoxib and sumatriptan, and parecoxib was more effective than sumatriptan. Only a significant difference between rizatriptan and sumatriptan was found after 60 and 120 minutes. This trial demonstrates the effectiveness of a parecoxib infusion in the treatment of acute migraine and that the circumvention of the first pass effect of the liver by rizatriptan may be beneficial for fast pain relief. PMID:21996647

  10. Vitamin E TPGS conjugated carbon nanotubes improved efficacy of docetaxel with safety for lung cancer treatment.

    PubMed

    Singh, Rahul Pratap; Sharma, Gunjan; Sonali; Singh, Sanjay; Kumar, Mohan; Pandey, Bajarangprasad L; Koch, Biplob; Muthu, Madaswamy S

    2016-05-01

    The aim of this work was to develop multi-walled carbon nanotubes (MWCNT), which were coated or covalently conjugated with d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), and loaded docetaxel as a model drug for effective treatment to lung cancer in comparison with the commercial docetaxel injection (Docel™). The human lung cancer cells (A549 cells) were employed as an in-vitro model to access cellular uptake, cytotoxicity, cellular apoptosis, cell cycle analysis, and reactive oxygen species (ROS) study of the docetaxel/coumarin-6 loaded MWCNT. The safety of MWCNT formulations were studied by the measurements of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the TPGS conjugated MWCNT could be 80 folds more effective than Docel™ after 24h treatment with the A549 cells. Flow cytometry analysis confirmed that cancerous cells were appeared significantly (P<0.05) in the sub G1 phase for TPGS conjugated MWCNT. Results of TPGS conjugated MWCNT have showed better efficacy with safety than non-coated or TPGS coated MWCNT and Docel™. PMID:26895505

  11. Efficacy of traditional treatment regimen on Kati Shoola with special reference to lumbar spondylolisthesis

    PubMed Central

    Ediriweera, E. R. H. S. S.; Gunathilka, H. D. P.; Weerasinghe, K. D. C. M.; Kalawana, O. T. M. R. K. S. B.

    2013-01-01

    According to Ayurveda, Kati Shoola is a disease with pain in lumbar region. Lumbar spondylolisthesis, anterior displacement of a vertebra or the vertebral column in relation to the vertebrae below, is one of the common causes. Current case study was carried out at Ayurveda Teaching hospital, Borella, to evaluate the efficacy of a treatment regimen used by Sri Lankan traditional physician family “Weerasinghe.” A 59-year-old female with a 9-month history of lumbar spondylolisthesis was treated with this regimen. The patient had progressive pain in left lower back, right and left buttocks, and difficulty in bending forward over 5°. X-ray of lumbo sacral region indicated that patient was suffering from Grade 3 lumbar spondylolisthesis. She was treated for 65 days with four treatment packages consisting of 13 prepared medicines. The response to the treatment was recorded and therapeutic effects were evaluated through symptomatic relief. Clinical symptoms were significantly reduced and degree of anterior flexion increased from 5° to 90°. However, X-rays indicated that the patient was still suffering from Grade 3 lumbar spondylolisthesis. This regimen is effective in successfully treating Kati Shoola (lumbar spondylolisthesis) by helping to reduce the symptoms and improving the degree of anterior flexion. PMID:24049411

  12. Comparison of efficacy of alternative medicine with allopathy in treatment of oral fungal infection

    PubMed Central

    Maghu, Sahil; Desai, Vela D.; Sharma, Rajeev

    2015-01-01

    This clinical study assessed and compared the efficacy of tea tree oil (TTO), an alternative form of medicine, with clotrimazole (i.e., allopathy) and a conservative form of management in the treatment of oral fungal infection. In this interventional, observational, and comparative study, we enrolled 36 medically fit individuals of both sexes who were aged 20–60 years old. The participants were randomly assigned to three groups. Group I was given TTO (0.25% rinse) as medicament, Group II was given clotrimazole, and Group III was managed with conservative treatment. The results were analyzed from the clinical evaluation of lesions, changes in four most common clinical parameters of lesions, and subjective symptoms on periodic follow-up. Based on the results, the percentage efficiency of the two groups were taken and compared through a bar graph on the scale of 1. No toxicity to TTO was reported. Group I (TTO) was found to be more efficient than the other two groups, as changes in four parameter indices of lesions were noted, and results for all three groups were compared on a percentage basis. The study concluded that TTO, being a natural product, is a better nontoxic modality compared to clotrimazole, in the treatment of oral fungal infection and has a promising future for its potential application in oral health products. PMID:26870682

  13. Efficacy of biological agents administered as monotherapy in rheumatoid arthritis: a Bayesian mixed-treatment comparison analysis

    PubMed Central

    Migliore, Alberto; Bizzi, Emanuele; Egan, Colin Gerard; Bernardi, Mauro; Petrella, Lea

    2015-01-01

    Background Biological agents provide an important therapeutic alternative for rheumatoid arthritis patients refractory to conventional disease-modifying antirheumatic drugs. Few head-to-head comparative trials are available. Purpose The aim of this meta-analysis was to compare the relative efficacy of different biologic agents indicated for use as monotherapy in rheumatoid arthritis. Methods A systemic literature search was performed on electronic databases to identify articles reporting double-blind randomized controlled trials investigating the efficacy of biologic agents indicated for monotherapy. Efficacy was assessed using American College of Rheumatology (ACR) 20, 50, and 70 criteria at 16–24 weeks. Relative efficacy was estimated using Bayesian mixed-treatment comparison models. Outcome measures were expressed as odds ratio and 95% credible intervals. Results Ten randomized controlled trials were selected for data extraction and analysis. Mixed-treatment comparison analysis revealed that tocilizumab offered 100% probability of being the best treatment for inducing an ACR20 response versus placebo, methotrexate, adalimumab, or etanercept. Likewise, for ACR50 and ACR70 outcome responses, tocilizumab had a 99.8% or 98.7% probability of being the best treatment, respectively, compared to other treatments or placebo. Tocilizumab increased the relative probability of being the best treatment (vs methotrexate) by 3.2-fold (odds ratio: 2.1–3.89) for all ACR outcomes. Conclusion Tocilizumab offered the greatest possibility of obtaining an ACR20, ACR50, and ACR70 outcome vs other monotherapies or placebo. PMID:26366085

  14. Microbicidal efficacy of an advanced oxidation process using ozone/hydrogen peroxide in water treatment.

    PubMed

    Sommer, R; Pribil, W; Pfleger, S; Haider, T; Werderitsch, M; Gehringer, P

    2004-01-01

    The combined application of ozone and hydrogen peroxide represents a kind of advanced oxidation for water treatment. The radicals that are generated during the process are used for the degradation of organic pollutants from groundwater and industrial effluents. The aim of our study was to evaluate the possible microbicidal, and particularly virucidal, efficacy of such a process, since no substantial data were available. The investigations were performed at a pilot plant installed for the elimination of perchloroethylene from polluted groundwater (reduction efficacy for perchloroethylene from 26 microg/L to 5 microg/L). To enable a reliable evaluation of the microbicidal effect, a set of alternate test organisms was used. As model viruses we chose bacteriophages MS2 (F+ specific, single-stranded RNA), phiX174 (single-stranded DNA) and PRD-1 (coated, double-stranded DNA). Furthermore, spores of Bacillus subtilis were included as possible surrogates for protozoa and Escherichia coli as representative for traditional indicator bacteria used in water analysis. The microbicidal efficiency was compared to the inactivation by means of ozone under two standard conditions (20 degrees C): (a) 0.4 mg/L residual after 4 min and (b) 0.1 mg/L residual after 10 min. Surprisingly, a good microbicidal effect of the ozone/hydrogen peroxide process was found. This was somewhat unexpected, because we had assumed that the disinfection potential of ozone would have been interfered with by the presence of hydrogen peroxide. Escherichia coli and the three test viruses revealed a reduction of about 6-log. In contrast, spores of Bacillus subtilis showed after the total process a reduction of 0.4-log. These results matched the effect of the ozone treatment (a) with a residual of 0.4 mg/L after 4 min contact time (20 degrees C). The test condition (b) with a residual of 0.1 mg/L ozone after a contact time of 10 min at 20 degrees C gave a higher reduction of the B. subtilis spores (1.5-log

  15. Placebo use in pain management: The role of medical context, treatment efficacy, and deception in determining placebo acceptability.

    PubMed

    Kisaalita, Nkaku; Staud, Roland; Hurley, Robert; Robinson, Michael

    2014-12-01

    Placebo effects can act as powerful pain relievers. Although the ethics of therapeutic placebo use are highly controversial, recent evidence suggests that medical providers frequently utilize placebo treatments and patients may be open to these interventions in certain contexts. This investigation used a patient-centered approach to answer essential questions about placebo treatment acceptability. People with chronic musculoskeletal pain completed a placebo survey in which they rated their knowledge of placebo and its efficacy for alleviating pain, evaluated the acceptability of placebo analgesic interventions across several unique medical contexts, and responded to 6 different patient-physician treatment scenarios to assess the role of deception and placebo effectiveness on mood and provider trust. Results showed that participants had limited knowledge of placebo and its efficacy for alleviating pain. Placebo acceptability was highly dependent on the context of the intervention, as placebo treatments were considered acceptable when used as complementary/adjunct treatments and when no other established treatments were available. Also, an analgesic placebo response mitigated the negative consequences of deception by improving provider trust and decreasing negative mood. These findings suggest that, contrary to popular belief, patients may be rather pragmatic in their appraisals of placebo treatment acceptability, and may consider a variety of treatments/contexts as ethically permissible for managing their pain. This is the first study of its kind to quantify perceptions of placebo analgesia knowledge and efficacy among individuals with chronic pain, and to assess the role of different medical contexts in treatment acceptability.

  16. Efficacy and safety of sofosbuvir-based therapy for the treatment of chronic hepatitis C in treatment-naïve and treatment-experienced patients.

    PubMed

    Liu, Xi; Wang, Yawen; Zhang, Guanjun; Li, Na; Zhu, Qianqian; Chang, Hongyun; Han, Qunying; Lv, Yi; Liu, Zhengwen

    2014-08-01

    Sofosbuvir, a hepatitis C virus (HCV) NS5B polymerase inhibitor, is a new direct-acting antiviral for chronic HCV infection. This systematic review and proportional meta-analysis examined the efficacy and safety of sofosbuvir-based therapy for chronic HCV infection in treatment-naïve and -experienced patients. Medline, Cochrane Database of Systematic Reviews, EMBASE and Web of Science databases were searched. Clinical trials examining sofosbuvir plus ribavirin (RBV) and pegylated interferon-α (peg-IFN) or sofosbuvir plus RBV among adults with chronic HCV infection were included. Data were extracted on virological responses including sustained virological response at post-treatment Week 12 (SVR12), relapse, treatment discontinuation due to an adverse event (AE), virological breakthrough during treatment, and AEs. One trial and 13 treatment arms/cohorts from seven studies met the criteria for analysis in treatment-naïve patients who were treated with sofosbuvir, RBV and peg-IFN; the SVR12 was 89% (95% CI 85-92%), relapse was 5% and the serious adverse event (SAE) rate was 4%. Six treatment arms/cohorts met the criteria for analysis in treatment-naïve patients who were treated with sofosbuvir and RBV; the SVR12 was 72% (95% CI 60-81%), relapse was 27% and the SAE rate was 3%. Three treatment arms/cohorts met the criteria for analysis in treatment-experienced patients who were treated with sofosbuvir and RBV; the SVR12 was 51% (95% CI 27-75%), relapse was 46% and the SAE rate was 4%. In conclusion, sofosbuvir-based treatment is effective and safe in treating chronic HCV infection, although the SVR12 of its combination with RBV, especially in treatment-experienced patients, requires improvement.

  17. Evaluation of the pharmacotherapeutic efficacy of Garcinia cambogia plus Amorphophallus konjac for the treatment of obesity.

    PubMed

    Vasques, Carlos A R; Rossetto, Simone; Halmenschlager, Graziele; Linden, Rafael; Heckler, Eliane; Fernandez, Maria S Poblador; Alonso, José L Lancho

    2008-09-01

    Hydroxycitric acid (HCA), the main compound of Garcinia cambogia extract, is a competitive blocker of ATP-citrate-lyase, presenting a potential inhibition of fatty acid biosynthesis. Glucomannan fibers, abundant in Amorphophallus konjac, seem to reduce the absorption kinetics of dietary fat. Therefore, the aim of this double-blind randomized study was to evaluate the pharmacotherapeutic efficacy of standardized extracts of G. cambogia (52.4% HCA) plus A. konjac (94.9% glucomannan) in the treatment of obesity. Fifty-eight obese subjects (BMI 30.0-39.9 kg/m(2)) were assigned to the placebo group (n = 26) or the treatment group (n = 32); no dietary restrictions were applied. Over a 12-week period, subjects were given daily doses of either Garcinia (2.4 g) plus Konjac (1.5 g) or placebo prior to their main meals (3 times/day). Before the start of treatment, and every 4 weeks thereafter, the following were recorded: height, weight, circumferences and body composition, resting energy expenditure (REE), lipid profile and glucose levels. The treatment had no significant effect on anthropometric parameters, REE, triglycerides or glucose levels. However, a significant reduction was observed in total cholesterol (-32.0 +/- 35.1 mg/dL) and LDL-c levels (-28.7 +/- 32.7 mg/dL) in the treated group, the final levels being significantly lower than those of the placebo group (p = 0.008 and p = 0.020, respectively). The results obtained suggest that the treatment had a significant hypocholesterolemic effect, without influencing the anthropometric or calorimetric parameters tested. PMID:18729243

  18. Topical treatments for seasonal allergic conjunctivitis: systematic review and meta-analysis of efficacy and effectiveness

    PubMed Central

    Owen, Christopher G; Shah, Anupa; Henshaw, Katherine; Smeeth, Liam; Sheikh, Aziz

    2004-01-01

    Background: Evidence for the effectiveness of topical treatments, in providing symptomatic relief from ocular allergy, remains uncertain. Aims: To assess the effectiveness and relative efficacy of topical treatments for the management of seasonal allergic conjunctivitis. Design of study: A systematic review and meta-analysis. Setting: A literature search of the Cochrane Library, Medline, and EMBASE bibliographic databases. Method: Double-masked randomised controlled trials were identified, that compared the use of topical mast cell stabilisers (sodium cromoglycate, nedocromil, lodoxamide) with placebo, topical antihistamines with placebo, and topical mast cell stabilisers with topical antihistamines. Results: A meta-analysis of six trials showed that patients using sodium cromoglycate were 17 times (95% confidence interval [CI] = 4 to 78) more likely to perceive benefit compared with those using a placebo, although this estimate may be partially influenced by publication bias. Five trials indicated that those patients using nedocromil were 1.8 times (95% CI = 1.3 to 2.6) more likely to perceive their allergy to be moderately or totally controlled than those using a placebo. Four trials showed that those using antihistamines were 1.3 times (95% CI = 0.8 to 2.2) more likely to perceive a ‘good’ treatment effect than those using mast cell stabilisers, although this beneficial effect was not statistically significant. Limited evidence suggests that antihistamines might have a faster therapeutic effect compared to mast cell stabilisers. Conclusion: Overall, these findings confirm the benefit of topical mast cell stabilisers and antihistamines over placebo for the treatment of allergic conjunctivitis. There is, however, insufficient evidence to recommend the use of one type of medication over another. Treatment preferences should therefore be based on convenience of use (with reduced frequency of instillation for some preparations), patient preference, and costs

  19. Evaluation of the efficacy of 2% Ocimum sanctum gel in the treatment of experimental periodontitis

    PubMed Central

    Hosadurga, Rajesh Ramesh; Rao, Sudarshan Narayan; Edavanputhalath, Rejeesh; Jose, Jobin; Rompicharla, Narayana Charyulu; Shakil, Moidin; Raju, Shashidhara

    2015-01-01

    Introduction: One of the options for the treatment of periodontitis is local drug delivery systems (LDD). Tulsi (Ocimum sanctum), a traditional herb, has many uses in medicine. It could be a suitable agent as LDD for the treatment of periodontitis. Aim: The aim was to formulate, evaluate the anti-inflammatory activity; assess duration of the action and the efficacy of 2% tulsi (O. sanctum) gel in the treatment of experimental periodontitis in Wistar Albino rat model. Settings and Design: Thirty six Wistar albino rats were randomly assigned to 3 groups. Periodontitis was induced using ligature model. Group 1-control; Group 2-Plain gel and Group 3-2% tulsi (O. sanctum) gel. Materials and Methods: 2% tulsi (O. sanctum) gel were prepared. The anti-inflammatory activity and duration of action were assessed. Silk ligature 5-0 was used to induce periodontitis. Gingival index (GI) and probing pocket depth were measured. Treatment was done. The rats were sacrificed. Morphometric analysis was done using Stereomicroscope and ImageJ software. Statistical Analysis Used: ANOVA followed by Bonferroni's test, Wilcoxon's test for intergroup comparison, Mann-Whitney test for P value computation was used. The observations are mean ± standard deviation and standard error of the mean. P < 0.01 as compared to control was considered as statistically significant. Results: 2% tulsi (O. sanctum) gel showed 33.66% inhibition of edema and peak activity was noted at 24 h. There was statistically significant change in the GI and probing pocket depth. Morphometric analysis did not show any significant difference between groups. No toxic effects were seen on oral administration of 2000 mg/kg of Tulsi extract. Conclusions: 2% tulsi (O. sanctum) gel was effective in the treatment of experimental periodontitis. PMID:25599031

  20. Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma

    PubMed Central

    KHOJA, LEILA; ATENAFU, ESHETU G.; YE, QIAN; GEDYE, CRAIG; CHAPPELL, MARYANNE; HOGG, DAVID; BUTLER, MARCUS O.; JOSHUA, ANTHONY M.

    2016-01-01

    Approved by the Food and Drug Administration in 2011, the anti-cytotoxic T-lymphocyte-associated protein 4 checkpoint inhibitor ipilimumab has delivered a survival benefit of ≥3 years in a subset of metastatic melanoma patients. After participating in the registration trial, patients were treated with this agent in routine practice. Toxicity and efficacy of agents in “real world” settings may differ from trials. The present study aimed to evaluate, with respect to toxicity and outcome, all patients treated with ipilimumab to date at the Princess Margaret Hospital (Toronto, Canada). Patients treated with ipilimumab between 2008 and 2013 were identified, and patient characteristics (age, gender, tumour burden, oncogenic mutation status, number of treatments received and toxicities from treatment) were collected. Progression-free survival (PFS) and overall survival (OS) were calculated from the commencement of ipilimumab treatment. Associations between clinical characteristics and outcome or toxicity were assessed. Between 2008 and 2013, 129 patients with metastatic cutaneous melanoma were treated. Since, during this period, ipilimumab was approved in the second line setting, ipilimumab was delivered in the second or subsequent line in all patients, and 70% did not receive any further anticancer therapy. Immune-related toxicities were observed, the onset of which varied from 1 to 162 days. The majority resolved within 6 weeks of the final treatment, with the exception of endocrinopathies and bowel related toxicity. The median PFS and OS were 2.83 and 8.44 months, respectively. No pre-treatment factor independently predicted toxicity. The number of infusions (4 vs. ≤3) and presence of toxicity were significantly associated with superior survival. The onset of toxicity secondary to ipilimumab could occur later than previously reported. Toxicities were manageable, but required long-term vigilance. PMID:26893783

  1. Effect of chronic feline immunodeficiency infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection.

    PubMed

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-03-01

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection. Six cats chronically infected with FIV-Glasgow8 (group A) and six FIV-free cats (group B) were infected with 'Candidatus M. haemominutum' on day 0 by intravenous inoculation of blood. From day 0 to 105 post-infection (pi), blood samples were collected for 'Candidatus M. haemominutum' and FIV provirus quantitative real-time polymerase chain reaction (PCR) and haematological examination. Three of the six cats in each of the groups were randomly selected to receive marbofloxacin treatment (2mg/kg PO SID) from day 49 to day 76 pi, with the remaining cats being untreated controls. Maximum 'Candidatus M. haemominutum' copy number was reached around day 30 pi. No overt cycling or marked variation in copy number was observed. No significant effect of FIV infection on 'Candidatus M. haemominutum' copy number kinetics or anaemia indices was found. No correlation was found between FIV provirus copy number and 'Candidatus M. haemominutum' copy number or haematological variables. Although marbofloxacin treatment was associated with a significant decrease in 'Candidatus M. haemominutum' copy number, the copy number plateaued during treatment, with no negative PCR results. Additionally, after termination of marbofloxacin treatment the copy numbers of the treated cats increased to reach levels similar to those of the untreated cats within 7-10 days. This study documents, for the first time, the infection kinetics and antibiotic responsiveness of 'Candidatus M. haemominutum' infection.

  2. Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection.

    PubMed

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-10-31

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection. Six cats chronically infected with FIV-Glasgow8 (Group X) and six FIV-free cats (Group Y) were infected with M. haemofelis on Day 0 by intravenous blood inoculation. From Day 0 until Day 86 post-infection (pi), blood samples were collected for M. haemofelis and FIV provirus quantitative real-time PCR and haematology. Three of the six cats in each of Groups X and Y were randomly selected to receive marbofloxacin treatment (2 mg/kg PO q24 h) from Day 16 to 43 pi, with the remaining cats being untreated controls with no antibiotic treatment. The M. haemofelis copy numbers and haematological data were compared between Groups X and Y, and between marbofloxacin-treated and control cats using a Mann-Whitney U-test. M. haemofelis infection was associated with development of macrocytic hypochromic anaemia. In some cats, marked variation in M. haemofelis copy number over time (>100,000-fold difference within 48 h in some cats) and/or cycling of copy number was seen. No correlation was found between FIV provirus copy number and M. haemofelis copy number or haematological variables. No significant effect of chronic FIV infection on M. haemofelis copy number kinetics or haematological changes due to M. haemofelis infection was found, other than MCHC (P=0.03). Marbofloxacin treatment was associated with a significant decrease in M. haemofelis copy number (P=0.002), although consistent clearance of infection was not demonstrated. This study reveals the presence of marked fluctuations in M. haemofelis copy number kinetics in vivo and a significant response to marbofloxacin antibiotic treatment.

  3. [Efficacy of tianeptine in the treatment of psychasthenia. A study versus placebo].

    PubMed

    Grivois, H; Deniker, P; Ganry, H

    1992-01-01

    Tianeptine is an effective antidepressant with original neurochemical properties. Tianeptine increases the serotonin (5-HT) reuptake after acute and chronic treatment. The efficacy of tianeptine (T) versus placebo (P) was evaluated in the treatment of psychasthenia, because of the role of 5-HT in obsessive-compulsive disorders, the last state of psychasthenia in term of severity. Patients were recruited using the psychasthenia scale; then, their MADRS scores limited those who turned out to the depression. Mean inclusion MADRS scores where 12 (T) and 11.8 (P). Tianeptine is an effective treatment for patients suffering from psychasthenia. Tianeptine is more effective than placebo in global score and in sub-scores (asthenia and somatic symptoms) of the psychasthenia scale. In spite of weak inclusion scores in MADRS, patients taking tianeptine also showed significant improvement, greater than with placebo. The percentage of patients with a reduction equal to or greater than 50% of their MADRS score was significantly more important in tianeptine group. These results could be the illustration of the decrease in associated depressive symptoms or the result of an improvement of symptoms common to MADRS and psychasthenia scales. The same favorable results were obtained in symptoms of anxiety scored by HARS. In term of safety, tianeptine is equivalent to a placebo if we consider somatic complaints expressed by the patients, global improvement evaluated by the patient and the investigator, weight and blood pressure. Interruption of treatment for side-effects concerns the placebo group only (3 versus 0). This excellent safety is particularly well-adapted to the treatment of these out-patients.

  4. Kinetics of venom and antivenom serum and clinical parameters and treatment efficacy in Bothrops alternatus envenomed dogs.

    PubMed

    Jacome, Do; Melo, M M; Santos, M M B; Heneine, L G D

    2002-12-01

    Dogs envenomed with non-lethal doses of Bothrops alternatus venom received standard antivenom therapy, im injections of flunixin meglumine, or topical treatmentwith aqueous Curcuma longa plant extract. Biodistribution of the venom and antivenom were determined by ELISA. There was no significant difference in the efficacy of antivenom and plant extract on local effects; flunixin treatment had lower efficacy. Distribution of the venom was similar with all 3 treatments. Serum levels of the antivenom reached maximum 2-4 h after administration and were not detected after the 5th d.

  5. Efficacy and Safety of Atomoxetine in the Treatment of Children and Adolescents with Attention Deficit Hyperactivity Disorder

    PubMed Central

    Kohn, Michael R.; Tsang, Tracey W.; Clarke, Simon D.

    2012-01-01

    Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication. PMID:23641171

  6. Efficacy of topical treatment of pigmentation skin disorders with plant hydroquinone glucosides as assessed by quantitative color analysis.

    PubMed

    Clarys, P; Barel, A

    1998-06-01

    Hydroquinone is a well known reagent used in the treatment of pigmentation disorders. The instability of the quinones and the required active concentration make topical treatment rather difficult. We tested the efficacy of an ascorbate-phytohydroquinone complex that inhibits the synthesis of melanin and promotes the degradation of the existing melanin. Lentigo senile lesions were evaluated before and after 1 month of treatment. Objective skin color evaluation was performed instrumentally. After one month of treatment, a clear depigmentation of the macules was measured. None of the volunteers reported any side effects from the prolonged treatment with the hydroquinone containing product. PMID:9675352

  7. Treatment outcome and efficacy of an aligner technique – regarding incisor torque, premolar derotation and molar distalization

    PubMed Central

    2014-01-01

    Background The aim of this study was to investigate the efficacy of orthodontic treatment using the Invisalign® system. Particularly, we analyzed the influence of auxiliaries (Attachment/Power Ridge) as well as the staging (movement per aligner) on treatment efficacy. Methods We reviewed the tooth movements of 30 consecutive patients who required orthodontic treatment with Invisalign®. In all patients, one of the following tooth movements was performed: (1) Incisor Torque >10°, (2) Premolar derotation >10° (3) Molar distalization >1.5 mm. The groups (1)-(3) were subdivided: in the first subgroup (a) the movements were supported with the use of an attachment, while in the subgroup (b) no auxiliaries were used (except incisor torque, in which Power Ridges were used). All tooth movements were performed in a split-mouth design. To analyze the clinical efficacy, pre-treatment and final plaster cast models were laser-scanned and the achieved tooth movement was determined by way of a surface/surface matching algorithm. The results were compared with the amount of tooth movement predicted by ClinCheck®. Results The overall mean efficacy was 59% (SD = 0.2). The mean accuracy for upper incisor torque was 42% (SD = 0.2). Premolar derotation showed the lowest accuracy with approximately 40% (SD = 0.3). Distalization of an upper molar was the most effective movement, with efficacy approximately 87% (SD = 0.2). Conclusion Incisor torque, premolar derotation and molar distalization can be performed using Invisalign® aligners. The staging (movement/aligner) and the total amount of planned movement have an significant impact on treatment efficacy. PMID:24923279

  8. Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model

    PubMed Central

    Long, L.; Hager, C.

    2016-01-01

    The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, the in vivo efficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with a P value of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding. PMID:26833160

  9. ASSESSMENT OF WARFARIN TREATMENT EFFICACY BY MEANS; OF USING COAGULATION TEST RESULTS WITHIN THE THERAPEUTIC RANGE.

    PubMed

    Varim, P; Varim, C; Ergenç, H; Uyanık, M; Yaylacı, S; Vatan, M; Gündüz, H

    2016-06-01

    Time in Therapeutic Range (TTR) is a value used to assess the efficacy of Warfarin treatment. The aim of our study is to determine the effective INR levels and the rate of TTR in patients on Warfarin regimen due to Atrial Fibrillation (AF) or Mechanical Prosthetic Valve (MPV). A total of 94 patients (58 female, and 36 male, mean age: 64.9±11years) on Warfarin treatment due to AF or MPV with at least 10 INR levels measurements in the last 6 months were included in this retrospective study. The patients were divided into 2 groups. Group 1 consisted of the patients with Valvular AF (n=47); Group 2 included the patients with Non-Valvular AF (n=47); TTR and INR levels were compared. The average of INR values were found as 2,4 (min: 1,3, max: 4,3) in all patients; 2,3 (min: 1,3, max: 4,2) in Group 1; 2,6 (min: 1,3, max: 4,3) in Group 2. The average of TTR values was found 40.3% (min: 10%, max: 80%) in all patients; 43.8% (min: 10%, max: 80%) in Group 1; 36,8% (min: 10%, max: 80%) in Group 2. INR and TTR values are needed to assess the effectiveness of the Warfarin treatment. The patients in treatment with Warfarin should be well trained and frequently monitored. On the other hand, the underlying factors of the TTR values being determined as lower in the Turkish patient population might be due to the lower socio-economic and socio-cultural status, inadequate education levels, and the insufficient information on use of the medication provided by the doctors to the patients. PMID:27441538

  10. Efficacy of treatments and pain management for trapeziometacarpal (thumb base) osteoarthritis: protocol for a systematic review

    PubMed Central

    Hamasaki, Tokiko; Lalonde, Lyne; Harris, Patrick; Bureau, Nathalie J; Gaudreault, Nathaly; Ziegler, Daniela; Choinière, Manon

    2015-01-01

    Introduction The thumb is essential for daily activities. Unfortunately, this digit is commonly affected by trapeziometacarpal osteoarthritis (TMO), handicapping a large number of individuals. TMO constitutes an increasing human and economic burden for our society whose population is ageing. Limited access to adequate treatment is among the most important obstacles to optimal TMO management. Poor understanding of TMO characteristics, lack of knowledge about evidence-based treatments, simplistic pain management plans based solely on the patient's physical condition, absence of interprofessional communication and lack of multidisciplinary treatment guidelines contribute to inadequate TMO management. On the long term, our research project aims at improving the quality of care and services offered to patients with TMO by developing a patient-centred, evidence-based multidisciplinary management clinical pathway coordinated across the healthcare system. This proposed systematic review is a prerequisite to ensuring evidence-based practices and aims to document the efficacy of all the existing modalities for TMO management. Methods and analysis The protocol of the systematic review is registered with PROSPERO and will be conducted using the guidelines Cochrane Handbook for Systematic Reviews of Interventions. We will identify studies in English and French concerning TMO treatments through searches in Cochrane Central, EMBASE, MEDLINE, PsychINFO, CINHAL, PubMed, OT Seekers, PEDRO and the grey literature. 2 reviewers will independently screen study eligibility, extract data and appraise studies using published assessment tools. Meta-analyses will be undertaken where feasible; otherwise, narrative syntheses will be carried out. The robustness of evidence will be assessed using the GRADE system. Ethics and dissemination Ethics approval is not required for this study. A comprehensive knowledge exchange and transfer plan incorporating effective strategies will be used to

  11. Melatonin’s Effect on the Efficacy of Desmopressin in the Treatment of Enuresis

    PubMed Central

    Sbordone, Annamaria; Cutrona, Costanza; Ianniello, Francesca; Guadagno, Chiara; Perrone, Giacomo; Chiaretti, Antonio; Verrotti, Alberto; Lazzaro, Vincenzo Di

    2016-01-01

    Purpose This study aims to evaluate and compare the efficacy of exogenous melatonin associated with desmopressin (dDAVP) and dietary recommendations. Methods A total of 189 patients were enrolled from the Service of Pediatrics, Campus Bio-Medico University Hospital of Rome, from January 2013 to June 2015. Of the 189 original patients, 153 children, aged between 5 and 14 years (mean age, 8.7 years) were included in the study. After clinical evaluation and a 3-month period of observation without treatment, children were assigned to receive treatment in one of 3 groups: group 1, dDAVP at a dose of 120 mcg a day (Minirin); group 2, dDAVP at a dose of 120 mcg and dietary recommendations; or group 3, dDAVP at a dose of 120 mcg, dietary recommendations, and melatonin at a dose of 1 mg a day (Melamil plus). Each patient was treated for 3 months. Results After the 3 months of therapy, a desiderable response was achieved in 30 of 51 patients (58.82%) treated with dDAVP, 35 of 53 patients (66.04%) treated with dDAVP and dietary recommendations, and 35 of 49 patients (71.43%) treated with dDAVP, dietary recommendations, and melatonin. Conclusions Although not statistically significant, the results show that the association between dDAVP treatment with dietary recommendations and melatonin could be considered a safe and effective treatment of NE. Considering that the statistically insignificant results might be due to the small sample size, the study will be continued to increase the number of subjects. PMID:27706008

  12. Safety and efficacy of combined cyclophosphamide and rituximab treatment in recalcitrant childhood lupus.

    PubMed

    Ale'ed, Ashwaq; Alsonbul, Abdullah; Al-Mayouf, Sulaiman M

    2014-04-01

    To report the safety and efficacy of combined cyclophosphamide and rituximab treatment in Saudi children with systemic lupus erythematosus (SLE). Medical records of all children with SLE treated with cyclophosphamide and rituximab between June 2007 and June 2012 at King Faisal Specialist Hospital and Research Center, Riyadh, were reviewed for demographic characteristics, age at diagnosis, concomitant treatments, indication of using rituximab and adverse events during the treatment period. Clinical and serologic response parameters included SLE Disease Activity Index (SLEDAI), complement, anti-ds DNA antibody and ANA levels, and mean daily corticosteroid dose assessed 3 months before combined cyclophosphamide and rituximab infusion course and at 6-month interval afterward. Sixteen patients (13 girls) with refractory SLE treated with cyclophosphamide and rituximab were included. The mean age at onset of SLE was 7.8 + 3.3 years, while the mean age at diagnosis was 8.1 + 3.4 years; the mean disease duration was 4.7 + 3.2 years. All patients were treated with corticosteroid and immunosuppressive drugs. Nephritis (8 patients) was the most frequent indication; other indications included refractory arthritis, thrombocytopenia, severe mucocutaneous lesions and central nervous system involvement. All patients received 2 doses, but 4 required 4-8 extra doses. All patients showed improvement in response parameters. There was significant reduction in SLEDAI (P < 0.0002) and corticosteroid dose (P < 0.005). A total of 4 adverse events were notified; 2 developed infusion-related reactions. One patient had severe soft tissue fungal infection, and other patient had pancreatitis. Our data showed beneficial therapeutic and steroid-sparing effects of rituximab as adjunctive treatment for children with refractory SLE including both renal and extrarenal manifestations. Although rituximab was well tolerated by the majority of patients, it may associated with various adverse events.

  13. The early efficacy of Heller myotomy in the treatment of Iranian patients with achalasia

    PubMed Central

    Abdi, Saeed; Forotan, Mojgan; Nikzamir, Abdolrahim; Zomorody, Saeedeh; Jahani-Sherafat, Somayeh

    2016-01-01

    Aim: The purpose of this study was to determine the efficacy of Heller myotomy for the treatment of achalasia in a referral center in Tehran, and investigate the clinical characteristics, manometric results and treatment responses among three achalasia subtypes in Iranian patients. Background: Esophageal achalasia is an unusual swallowing disorder, characterized by high pressure in the lower esophageal sphincter (LES) on swallowing, failure relaxation of the LES and the absence of peristalsis in esophageal. Patients and methods: In this cross sectional study, clinical symptom and esophageal manometry before and 2 months after treating with Heller myotomy in 20 patients with achalasia who were referred to Taleghani Hospital, Tehran, in 2013 were evaluated. Patients’ demographic, clinical features and response to treatment were analyzed using SPSS software (version 20, Chicago, IL, USA). Results: All the diagnostic criteria measured after the treatment were significantly different (P<0.05) before and after the therapy. The average decline in the length of the esophagus was 1.8 cm and dysphasia score was 7.25 units. Also an average decline in LES Resting Pressure, LES Residual Pressure, PIP, and IRP were 23.2 mmHg, 14.3 mmHg, 3.4 mmHg and 17.8 mmHg, respectively. Conclusion: Results of this study showed that the Heller myotomy is highly effective in relieving dysphasia in patients with achalasia. Also, type II achalasia is the most common subtype of achalasia with a better response to Heller myotomy compared to the other types. PMID:26744612

  14. Efficacy and toxicity of formalin solutions containing paraformaldehyde for fish and egg treatments

    USGS Publications Warehouse

    Howe, G.E.; Marking, L.L.; Bills, T.D.; Schreier, T.M.

    1995-01-01

    Formalin used for fish and egg treatments at hatcheries often develops a white precipitate called paraformaldehyde when stored at low temperatures. This presents a problem for hatchery managers because most of the literature and treatment procedures claim that formalin containing paraformaldehyde is more toxic than pure formalin and is not safe for fish or egg treatments. Acute toxicity tests with rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus) showed that the toxicity of formalin solutions containing a moderate amount of fine paraformaldehyde was similar to that of pure formalin. In efficacy tests on fish eggs, the bottom fraction of a formalin solution containing paraformaldehyde and a sample from the clear top fraction were equally effective in controlling fungal infection on rainbow trout eggs and caused no treatment-related mortality. Chemical assays found on average a 3% difference in formaldehyde concentration between top and bottom fractions of a formalin solution containing paraformaldehyde. We recommend normal use of formalin solutions containing light to moderate amounts of fine paraformaldehyde. Allowing solutions to warm to room temperature may resolubilize moderate amounts of paraformaldehyde if the exposure to cold was not prolonged. If precipitation is heavier, clear top fractions can be decanted and used as normal because paraformaldehyde settles to the bottom of containers. Formalin solutions that have been exposed to freezing temperatures for long periods (more than 6 weeks) and have developed large amounts of paraformaldehyde solids should not be used and resolubilization by warming is not possible. Formation of paraformaldehyde in formalin solutions can be easily avoided by storing formalin at room temperature.

  15. The Efficacy of Corticosteroids in the Treatment of Peritonsillar Abscess: A Meta-Analysis

    PubMed Central

    Lee, Yeon Ji; Jeong, Yeon Min; Lee, Ho Seok; Hwang, Se Hwan

    2016-01-01

    Despite widespread use of antibiotics and surgical procedures for treating peritonsillar abscess (PTA), symptoms of severe inflammation such as pain and trismus during treatment result in patient dissatisfaction. The goal of this study was to perform a systematic review and meta-analysis of the efficacy of systemic steroids on the clinical course of PTA. Two reviewers independently searched the databases (MEDLINE, Scopus, and the Cochrane Database) from inception to December 2014. Studies comparing systemic administration of steroids (steroid group) with placebo (placebo group), where the outcomes of interest were pain, body temperature, hospitalization, and oral intake during the posttreatment period, were included. Baseline study characteristics, study quality data, numbers of patients in the steroid and control groups, and outcomes were extracted. Sufficient data for meta-analysis were retrieved for 3 trials with a total of 153 patients. Pain-related parameters (patient-reported scores and trismus), body temperature, and dysphagia during the first 24 hours after treatment were significantly improved in the steroid group compared with placebo group. The discharge rate during the first 5 days of the posttreatment period was significantly higher in the steroid group than the control group. However, although more patients in the steroid group returned to normal activities and dietary intake at 24 hours after treatment, the differences between the groups were not significant and disappeared after 48 hours. In the treatment of PTA, systemic administration of steroids with antibiotics could reduce pain-related symptoms, as well as provide a benefit with respect to the clinical course. However, further trials with well-designed research methodologies should be conducted to confirm our results. PMID:27090283

  16. The efficacy of selamectin in the treatment of naturally acquired infestations of sarcoptes scabiei on dogs.

    PubMed

    Shanks, D J; McTier, T L; Behan, S; Pengo, G; Genchi, C; Bowman, D D; Holbert, M S; Smith, D G; Jernigan, A D; Rowan, T G

    2000-08-23

    Selamectin, a novel avermectin, was evaluated for its effect on naturally occurring infestations of Sarcoptes scabiei in 42 dogs. In two controlled and masked laboratory studies conducted in the USA and Italy, infested dogs received treatment with either selamectin (6mgkg(-1); range: 6-12mgkg(-1)) or the vehicle only (negative control). Treatments were administered topically to the skin on each animal's back at the base of the neck in front of the scapulae. Study day 0 was defined as the first day of treatment administration. Dogs were treated on days 0 and 30, and efficacy was assessed by counting viable mites recovered from skin scrapings performed on each dog on days 14, 29 or 30, 44, and 60, and by categorising the clinical signs of canine scabies on the same days. Percentage reductions in geometric mean mite counts for selamectin, compared with vehicle, on days 14, 29 or 30, 44, and 60 were > or =98.1, > or =93.5, 100, and 100%, respectively. Analysis of variance, confirmed by Savage Scores, showed that ln(mite counts+1) values for selamectin-treated dogs were significantly lower (P< or =0.0391) than those for vehicle-treated dogs on all post-treatment assessment days. Clinical signs of scabies were markedly reduced in selamectin-treated dogs, compared with vehicle-treated dogs. Topical administration to the skin in a single spot of a single unit dose of selamectin, or of two unit doses given 1 month apart, each providing at least the recommended minimum dosage of 6mgkg(-1), was highly effective against naturally acquired infestations of S. scabiei in dogs, reducing mite counts by >93% (single dose) and 100% (two doses).

  17. Efficacy of herbal tincture as treatment option for retained placenta in dairy cows.

    PubMed

    Cui, Dongan; Li, Jianxi; Wang, Xuezhi; Xie, Jiasheng; Zhang, Kai; Wang, Xurong; Zhang, Jingyan; Wang, Lei; Qin, Zhe; Yang, Zhiqiang

    2014-02-01

    Retained placenta remains therapeutic challenge in cattle. Certain traditional medicines are believed to be able to alleviate retained placenta condition and improve overall fertility in cows. The aim of the present study was to evaluate the efficacy of an herbal tincture for treatment of retained placenta. The herbal tincture was extracted from a combination of Herba Leonuri, Angelicae Sinensis Radix, Flos Carthami, Myrrha and Rhizoma Cyperi by percolation with 70% ethanol to a concentration of 0.5g crude herb/ml. Cows diagnosed with retained placenta (n=48) were randomly divided into one of two treatment groups (A and B), with animals in group A (n=26) receiving herbal tincture orally, and cows in group B (n=22) receiving oxytetracycline infusion into the uterus. Eighty six cows with no clinically visible pathological conditions, given birth alone and with no retained placenta diagnosis were included into control group (C). Retained placenta was expelled within 72h following initial treatment in 19 cows in group A, yet no cows in group B were recorded to expel placenta in the same time. The median number of days to first service (70.0 vs. 102.5 days; P<0.05) and median number of days open (76.0 vs. 134.0 days; P<0.01) were lower in group A than in group B. Percentage of cows pregnant within 100 days postpartum was the highest for animals in group A compared to controls (61.5% vs. 39.5%, P<0.05), and for animals in group B (61.5% vs. 22.7%; P<0.01). Herbal tincture used in the present study might facilitate expulsion of retained placenta and improve subsequent fertility, thus could present effective treatment option for retained placenta in cows.

  18. Turner syndrome in Albania and the efficacy of its treatment with growth hormone.

    PubMed

    Hoxha, Petrit; Babameto-Laku, Anila; Vyshka, Gentian; Gjoka, Klodiana; Minxuri, Dorina; Myrtaj, Elira; Çakërri, Luljeta

    2015-11-01

    The aim of this study was the evaluation of Turner syndrome inside the Albanian population, its clinical, cytological and genetic characteristics, the accompanying pathologies, and the efficacy of the treatment with the growth hormone. We performed a retrospective analysis of 59 patients suffering from this syndrome (aging from 5 to 23 years old). The diagnosis of female patients suffering from Turner syndrome is delayed, with a mean age at the moment of diagnosis of 13.74 years (5-23 years). The main reason for seeking medical advice was the growth retardation or a delayed puberty. Available data for 52 patients showed that the most frequent accompanying pathologies were the following: thyroid autoimmune disorders (59%), cardiovascular anomalies (43%), renal pathologies (41%), hearing impairment (4.3%) and hypertension (3.3%). Follow-up for the growth rate was possible for 52 patients out of the total of 59 patients. Twenty-five of the female patients suffering Turner syndrome and forming part of our study sample were treated with growth hormone for a period averaging 3 years and 4 months. A variety of reasons was identified as responsible for the missed treatment in 27 patients. We saw an enhanced growth (in terms of body height) within the treated subgroup, when compared with the untreated subgroup (27 patients), especially during the first 3 years of the follow-up. No side effects of this treatment were reported. Both groups of patients initiated as well a sexual hormone therapy (estrogens and progesterone) for inducing puberty at the age of 12 years. Further work is needed for an early diagnosis of this syndrome, the prompt treatment with growth hormone and the monitoring of accompanying disorders. This will ensure a better quality of life and an improvement of the longevity of patients suffering from the Turner syndrome. PMID:26181044

  19. Turner syndrome in Albania and the efficacy of its treatment with growth hormone.

    PubMed

    Hoxha, Petrit; Babameto-Laku, Anila; Vyshka, Gentian; Gjoka, Klodiana; Minxuri, Dorina; Myrtaj, Elira; Çakërri, Luljeta

    2015-11-01

    The aim of this study was the evaluation of Turner syndrome inside the Albanian population, its clinical, cytological and genetic characteristics, the accompanying pathologies, and the efficacy of the treatment with the growth hormone. We performed a retrospective analysis of 59 patients suffering from this syndrome (aging from 5 to 23 years old). The diagnosis of female patients suffering from Turner syndrome is delayed, with a mean age at the moment of diagnosis of 13.74 years (5-23 years). The main reason for seeking medical advice was the growth retardation or a delayed puberty. Available data for 52 patients showed that the most frequent accompanying pathologies were the following: thyroid autoimmune disorders (59%), cardiovascular anomalies (43%), renal pathologies (41%), hearing impairment (4.3%) and hypertension (3.3%). Follow-up for the growth rate was possible for 52 patients out of the total of 59 patients. Twenty-five of the female patients suffering Turner syndrome and forming part of our study sample were treated with growth hormone for a period averaging 3 years and 4 months. A variety of reasons was identified as responsible for the missed treatment in 27 patients. We saw an enhanced growth (in terms of body height) within the treated subgroup, when compared with the untreated subgroup (27 patients), especially during the first 3 years of the follow-up. No side effects of this treatment were reported. Both groups of patients initiated as well a sexual hormone therapy (estrogens and progesterone) for inducing puberty at the age of 12 years. Further work is needed for an early diagnosis of this syndrome, the prompt treatment with growth hormone and the monitoring of accompanying disorders. This will ensure a better quality of life and an improvement of the longevity of patients suffering from the Turner syndrome.

  20. Combined flubendazole-nitazoxanide treatment of cystic echinococcosis: Pharmacokinetic and efficacy assessment in mice.

    PubMed

    Laura, Ceballos; Celina, Elissondo; Sergio, Sánchez Bruni; Guillermo, Denegri; Carlos, Lanusse; Luis, Alvarez

    2015-08-01

    The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole, and the results have been shown to be highly variable. Thus, new and more efficient treatment options are urgently needed. The goals of the current study were: a) to compare the ex vivo activity of flubendazole (FLBZ) and nitazoxanide (NTZ), given either separately or co-administered, against Echinococcus granulosus protoscoleces and cysts, b) to characterize the plasma disposition kinetics of FLBZ administered alone or combined with NTZ in mice; (c) to compare the in vivo activity of FLBZ and NTZ (either each alone or as a combined treatment) against secondary CE developed in mice. Ex vivo drug activity study: E. granulosus protoscoleces and cysts were incubated either with FLBZ, NTZ, or the FLBZ-NTZ combination. Protoscoleces and cyst viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). Pharmacokinetic study: Balb/C mice received FLBZ (5 mg/kg) orally either alone or co-administered with NTZ (100 mg/kg). Blood samples were collected up to 12 h post treatment and plasma analyzed for FLBZ/metabolites by HPLC. Clinical Efficacy study: following secondary infection, meaning i.p. injection of 1500 E. granulosus protoscoleces/animal (n=40), the both drugs were administered by intragastric inoculation on a daily basis for a period of 25 days. Balb/C mice received FLBZ (5 mg/kg, twice a day) alone, NTZ (100 mg/kg, once daily) alone or a combination of both molecules (FLBZ, 5mg/kg twice a day and NTZ, 100 mg/kg, once daily). Ten untreated animals were used as a control. All animals were killed and the weight of the cysts collected from each animal was recorded. The presence of NTZ did not markedly affect the FLBZ kinetic parameters in mice. FLBZ alone or combined with NTZ induced a reduction (P<0.05) of cyst weight in comparison to the untreated control and NTZ-treated treated mice. The data obtained here indicate that NTZ did

  1. Combined flubendazole-nitazoxanide treatment of cystic echinococcosis: Pharmacokinetic and efficacy assessment in mice.

    PubMed

    Laura, Ceballos; Celina, Elissondo; Sergio, Sánchez Bruni; Guillermo, Denegri; Carlos, Lanusse; Luis, Alvarez

    2015-08-01

    The current chemotherapy of cystic echinococcosis (CE) is mainly based on the use of albendazole, and the results have been shown to be highly variable. Thus, new and more efficient treatment options are urgently needed. The goals of the current study were: a) to compare the ex vivo activity of flubendazole (FLBZ) and nitazoxanide (NTZ), given either separately or co-administered, against Echinococcus granulosus protoscoleces and cysts, b) to characterize the plasma disposition kinetics of FLBZ administered alone or combined with NTZ in mice; (c) to compare the in vivo activity of FLBZ and NTZ (either each alone or as a combined treatment) against secondary CE developed in mice. Ex vivo drug activity study: E. granulosus protoscoleces and cysts were incubated either with FLBZ, NTZ, or the FLBZ-NTZ combination. Protoscoleces and cyst viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). Pharmacokinetic study: Balb/C mice received FLBZ (5 mg/kg) orally either alone or co-administered with NTZ (100 mg/kg). Blood samples were collected up to 12 h post treatment and plasma analyzed for FLBZ/metabolites by HPLC. Clinical Efficacy study: following secondary infection, meaning i.p. injection of 1500 E. granulosus protoscoleces/animal (n=40), the both drugs were administered by intragastric inoculation on a daily basis for a period of 25 days. Balb/C mice received FLBZ (5 mg/kg, twice a day) alone, NTZ (100 mg/kg, once daily) alone or a combination of both molecules (FLBZ, 5mg/kg twice a day and NTZ, 100 mg/kg, once daily). Ten untreated animals were used as a control. All animals were killed and the weight of the cysts collected from each animal was recorded. The presence of NTZ did not markedly affect the FLBZ kinetic parameters in mice. FLBZ alone or combined with NTZ induced a reduction (P<0.05) of cyst weight in comparison to the untreated control and NTZ-treated treated mice. The data obtained here indicate that NTZ did

  2. Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications

    PubMed Central

    Chen, Min-Hua; Yang, Wei; Yan, Kun; Gao, Wen; Dai, Ying; Wang, Yan-Bin; Zhang, Xiao-Peng; Yin, Shan-Shan

    2005-01-01

    AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic malignant tumor and the relevant complications. METHODS: A total of 338 patients with 763 hepatic tumors underwent ultrasound-guided RFA (565 procedures). There were 204 cases of hepatic cellular carcinoma (HCC) with 430 tumors, the mean largest diameter was 4.0 cm. Of them, 48 patients (23.5%) were in stages I-II (UICC Systems) and 156 (76.5%) in stages III-IV There were 134 cases of metastatic liver carcinoma (MLC), with 333 metastases in the liver, the mean diameter was 4.1 cm, the liver metastases of 96 patients (71.6%) came from gastrointestinal tract. Ninety-three percent of the 338 patients were treated using the relatively standard protocol. Crucial attention must be paid to monitor the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structures injury in time. The tumors were considered as ablated completely, if no viability was found on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up for 3-57 mo. RESULTS: The ablation success rate was 93.3% (401/430 tumors) for HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors), respectively. A total of 137 patients (40.5%) underwent 2-11 times of repeated ablations because of tumor recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was 84.6%, 66.6%, and 63.1%, respectively; the survival rate from 48 patients of I-II stage HCC was 93.7%, 80.4%, and 80.4%, respectively. The major complication rate in this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safe alternative for the patients of hepatic malignant tumor, even of

  3. Efficacy of high-dose methylprednisolone pulse therapy in the treatment of enterovirus 71 encephalitis.

    PubMed

    Zhang, Guangyou; Wang, Jiwen; Yao, Guo; Shi, Baohai

    2016-07-01

    To investigate the efficacy of high-dose methylprednisolone pulse therapy in the treatment of Enterovirus 71 (EV71) encephalitis. To determine whether high-dose methylprednisolone pulse therapy should be used, 80 cases of pediatric patients with EV71 encephalitis were randomly divided into steroid pulse therapy group and non-steroid pulse therapy group and their clinical information was compared using statistic analysis. There was no statistical difference in the duration of fever, duration of nervous system involvement, duration of hospital stay, blood pressure, and cure rates between the two groups (p>0.05). The heart rate, respiratory rate, white blood cell counts and blood glucose of the steroid pulse therapy group were significantly higher than those of the non-steroid pulse therapy group (p<0.05). High-dose steroid pulse therapy to treat EV71 encephalitis can't shorten the course or improve the prognosis of the disease. In contrast, it has side effects and might aggravate disease condition or interfere with disease diagnosis. Our study suggested that there is no beneficial effect to use high-dose steroid pulse therapy for the treatment of EV71 encephalitis. PMID:27592493

  4. Efficacy of an oral hyaluronate and collagen supplement as a preventive treatment of elbow dysplasia

    PubMed Central

    García-López, Núria; Díaz-Ramos, Ana

    2014-01-01

    One hundred and five Labrador dogs were randomly divided into two groups to determine the number of animals that develop elbow dysplasia when treated with an oral supplement compared to untreated ones. Efficacy of the oral treatment was also evaluated once illness was diagnosed. The supplement (Hyaloral) contained hyaluronic acid, hydrolysed collagen, glucosamine, chondroitin sulphate, and gamma oryzanol. Clinical evaluation of the elbow joints was completed at months 3, 6, 12, and 20 by orthopaedic evaluations, radiography, serologic and blood analysis, and veterinarian evaluation of dysplasia symptoms. All side effects were recorded. In the control group, 33.3% of the dogs developed radiographic evidence of elbow dysplasia compared to 18.5% in the treated group. Symptoms of dysplasia at 12 months differed between the treated (12.5%) and control (61.5%) animals, and were significantly different at 20 months (p < 0.05). Differences in lameness along with movement and swelling of the elbows between groups were observed after 12 months. The treated group had improved significantly by the last visit (p < 0.05). No adverse side effects were reported. In conclusion, oral treatment with Hyaloral may have a potential cumulative action that provides protection against dysplasia and significantly improves symptoms of elbow dysplasia. PMID:25234322

  5. Efficacy of massage treatment technique in masseter muscle hardness: robotic experimental approach.

    PubMed

    Hiraiwa, Yuichiro; Ariji, Yoshiko; Kise, Yoshitaka; Sakuma, Shigemitsu; Kurita, Kenichi; Ariji, Eiichiro

    2013-10-01

    The study aimed to clarify the masseter muscle hardness in patients with myofascial pain, to examine their changes after massage, and to analyze whether the hardness can be an index for massage treatment. Sixteen patients with myofascial pain (12 with unilateral and 4 with bilateral masseter muscle pain) and 24 healthy volunteers were enrolled in this study. The masseter hardness between patients and the healthy volunteers was compared. The changes in the hardness in patients after massage were examined. The relation of the hardness with massage regimens and efficacies was analyzed. There was a significant right-and-left difference of the hardness in patients, although there was no difference in the healthy volunteers. The hardness decreased after massage. The pretreatment asymmetry index of the hardness showed a significant correlation with the massage pressure. It was concluded that there was a significant difference between the right and left masseter hardness in patients with myofascial pain. After massage treatment, the masseter hardness and right-and-left difference decreased. The hardness may be an index for determining the massage pressure. PMID:24308103

  6. [Efficacy of dolutegravir in treatment-experienced patients: the SAILING and VIKING trials].

    PubMed

    Moreno, Santiago; Berenguer, Juan

    2015-03-01

    Dolutegravir is an HIV integrase inhibitor with a high genetic barrier to resistance and is active against raltegravir- and/or elvitegravir-resistant strains. The clinical development of dolutegravir for HIV infection rescue therapy is based on 3 clinical trials. In the SAILING trial, dolutegravir (5 mg once daily) in combination with 2 other antiretroviral agents was well tolerated and showed greater virological effect than raltegravir (400 mg twice daily) in the treatment of integrase inhibitor-naïve adults with virological failure infected with HIV strains with at least two-class drug resistance. The VIKING studies were designed to evaluate the efficacy of dolutegravir as rescue therapy in treatment-experienced patients infected with HIV strains with resistance mutations to raltegravir and/or elvitegravir. VIKING-1-2 was a dose-ranging phase IIb trial. VIKING-3 was a phase III trial in which dolutegravir (50 mg twice daily) formed part of an optimized regimen and proved safe and effective in this difficult-to-treat group of patients. Dolutegravir is the integrase inhibitor of choice for rescue therapy in multiresistant HIV infection, both in integrase inhibitor-naïve patients and in those previously treated with raltegravir or elvitegravir.

  7. [Efficacy of dolutegravir in treatment-experienced patients: the SAILING and VIKING trials].

    PubMed

    Moreno, Santiago; Berenguer, Juan

    2015-03-01

    Dolutegravir is an HIV integrase inhibitor with a high genetic barrier to resistance and is active against raltegravir- and/or elvitegravir-resistant strains. The clinical development of dolutegravir for HIV infection rescue therapy is based on 3 clinical trials. In the SAILING trial, dolutegravir (5 mg once daily) in combination with 2 other antiretroviral agents was well tolerated and showed greater virological effect than raltegravir (400 mg twice daily) in the treatment of integrase inhibitor-naïve adults with virological failure infected with HIV strains with at least two-class drug resistance. The VIKING studies were designed to evaluate the efficacy of dolutegravir as rescue therapy in treatment-experienced patients infected with HIV strains with resistance mutations to raltegravir and/or elvitegravir. VIKING-1-2 was a dose-ranging phase IIb trial. VIKING-3 was a phase III trial in which dolutegravir (50 mg twice daily) formed part of an optimized regimen and proved safe and effective in this difficult-to-treat group of patients. Dolutegravir is the integrase inhibitor of choice for rescue therapy in multiresistant HIV infection, both in integrase inhibitor-naïve patients and in those previously treated with raltegravir or elvitegravir. PMID:25858609

  8. Efficacy of depression treatments for immigrant patients: results from a systematic review

    PubMed Central

    2014-01-01

    Background The unprecedented rates of global migration present unique challenges to mental health services in migrant receiving countries to provide efficacious and culturally salient treatment for mental health conditions including depression. This review aimed to identify and evaluate the effectiveness of depression interventions specifically directed towards first-generation immigrant populations. Methods We conducted a systematic review of original research published between 2000 and 2013 that investigated depression interventions in first generation immigrants. Results Fifteen studies were included; the majority focused on Latino immigrants living in the United States (US). Twelve studies investigated the use of psychotherapies; the remainder examined collaborative care models and physical exercise-based interventions. Cognitive Behavioral Therapy and Behavioral Activation tended to improve depressive symptoms, especially when culturally adapted to suit clients while Problem Solving Therapy improved depressive symptomology with and without adaptations. Collaborative care and exercise did not significantly improve depressive symptoms. Conclusion Depression may be effectively treated by means of psychotherapies, especially when treatments are culturally adapted. However the reviewed studies were limited due to methodological weaknesses and were predominantly undertaken in the US with Latino patients. To improve generalizability, future research should be undertaken in non-US settings, amongst diverse ethnic groups and utilize larger sample sizes in either randomized clinical trials or observational cohort studies. PMID:24930429

  9. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria

    PubMed Central

    Hillmen, Peter; Muus, Petra; Röth, Alexander; Elebute, Modupe O; Risitano, Antonio M; Schrezenmeier, Hubert; Szer, Jeffrey; Browne, Paul; Maciejewski, Jaroslaw P; Schubert, Jörg; Urbano-Ispizua, Alvaro; de Castro, Carlos; Socié, Gérard; Brodsky, Robert A

    2013-01-01

    Paroxysmal nocturnal haemoglobinuria (PNH) is characterized by chronic, uncontrolled complement activation resulting in elevated intravascular haemolysis and morbidities, including fatigue, dyspnoea, abdominal pain, pulmonary hypertension, thrombotic events (TEs) and chronic kidney disease (CKD). The long-term safety and efficacy of eculizumab, a humanized monoclonal antibody that inhibits terminal complement activation, was investigated in 195 patients over 66 months. Four patient deaths were reported, all unrelated to treatment, resulting in a 3-year survival estimate of 97·6%. All patients showed a reduction in lactate dehydrogenase levels, which was sustained over the course of treatment (median reduction of 86·9% at 36 months), reflecting inhibition of chronic haemolysis. TEs decreased by 81·8%, with 96·4% of patients remaining free of TEs. Patients also showed a time-dependent improvement in renal function: 93·1% of patients exhibited improvement or stabilization in CKD score at 36 months. Transfusion independence increased by 90·0% from baseline, with the number of red blood cell units transfused decreasing by 54·7%. Eculizumab was well tolerated, with no evidence of cumulative toxicity and a decreasing occurrence of adverse events over time. Eculizumab has a substantial impact on the symptoms and complications of PNH and results a significant improvement in patient survival. PMID:23617322

  10. Pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin for the treatment of respiratory infections.

    PubMed

    Chono, Sumio; Tanino, Tomoharu; Seki, Toshinobu; Morimoto, Kazuhiro

    2007-04-01

    The pharmacokinetic and pharmacodynamic efficacy of intrapulmonary administration of ciprofloxacin (CPFX) for the treatment of respiratory infections caused by pathogenic microorganisms resisting sterilization systems of alveolar macrophages (AMs) was evaluated by comparison with an oral administration. The time-courses of the concentration of CPFX in AMs and lung epithelial lining fluid (ELF) following intrapulmonary administration of CPFX solution to rats (200 microg/kg) were markedly higher than that following oral administration (10 mg/kg). The time-course of the concentrations of CPFX in plasma following intrapulmonary administration was markedly lower than that in AMs and ELF. These results indicate that intrapulmonary administration is more effective in delivering CPFX to AMs and ELF, compared with oral administration, in spite of a low dose and it avoids distribution of CPFX to the blood. In addition, the antibacterial effects of CPFX in AMs and ELF following intrapulmonary administration were evaluated by pharmacokinetics/pharmacodynamics analysis. The concentration of CPFX in AMs and ELF-time curve (AUC)/minimum inhibitory concentration of CPFX (MIC) ratio and the maximum concentration of CPFX in AMs and ELF (Cmax)/MIC ratio were markedly higher than the effective values. The present study indicates that intrapulmonary administration of CPFX is an effective technique for the treatment of respiratory infections.

  11. Efficacies of surgical treatments based on Harris hip score in elderly patients with femoral neck fracture

    PubMed Central

    Liang, Chengwei; Yang, Fengjian; Lin, Weilong; Fan, Yongqian

    2015-01-01

    Aim: To compare the efficacies of four surgical treatments, i.e., total hip arthroplasty (THA), internal fixation (IF), hemiarthroplasty (HA), and artificial femoral head replacement (artificial FHR), by performing a network meta-analysis based on Harris hip score (HHS) in elderly patients with femoral neck fracture. Methods: In strict accordance with specific inclusion and exclusion criteria, randomized controlled trails (RCTs) were screened and selected from a larger group of studies that were retrieved through a comprehensive search of scientific literature databases, further complimented by manual search. The resultant high-quality data from final selected studies were analyzed using Stata 12.0 software. Results: A total of 3680 studies were initially retrieved from database search, and 15 RCTs were eventually incorporated into this meta-analysis, containing 1781 elderly patients who had undergone various surgical treatments for femoral neck fracture (THA group = 604; HA group = 604; IF group = 495; artificial FHR group = 78). Our major result revealed a statistically significant difference in HHS of femoral neck fracture when HA and IF groups were compared with THA. No differences were detected in the HHS of femoral neck fracture undergoing artificial FHR and THA. The surface under the cumulative ranking curves (SUCRA) value of HHS, in elderly patients with femoral neck fracture after surgery, revealed that IF has the highest value. Conclusions: The current network meta-analysis results suggest that IF is the superlative surgical procedure for femoral neck fracture patients, and IF significantly improves the HHS in femoral neck fracture patients. PMID:26221216

  12. Evaporation versus iced peritoneal lavage treatment of heatstroke: comparative efficacy in a canine model.

    PubMed

    White, J D; Kamath, R; Nucci, R; Johnson, C; Shepherd, S

    1993-01-01

    The authors compared the speed of cooling and treatment efficacy for evaporative cooling versus iced peritoneal lavage in a canine heatstroke model. Nine random-source, mongrel dogs were anesthetized, shaved, and internally heated until the core temperature reached 43.0 degrees C. The animals were then randomly assigned to be cooled to 37 degrees C either by sterile normal saline (6 degrees C) continuous peritoneal lavage at 250 mL/min (n = 4), or by spraying with tap water (15 degrees C, 12 L/min) before a large fan blowing room temperature air (23 degrees C) across the dog at 0.5 m/sec from a height of 50 cm (n = 5). Temperatures were monitored by thermocouples in both tympanic membranes. Electrocardiogram, blood pressure, and pulse were continuously monitored. Evaporative cooling was as rapid as iced peritoneal lavage (0.18 +/- .03 versus 0.17 +/- .07 degrees C/min/m2, P = NS). All animals survived, although one animal in each treatment group demonstrated a moderate neurologic deficit when measured 48 hours following resuscitation. A simple noninvasive evaporative cooling technique, readily available in the emergency department, appears to be as rapid readily available in the emergency department, appears to be as rapid and effective as aggressive peritoneal lavage for cooling and treating heatstroke in the dog. PMID:8447861

  13. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension.

    PubMed

    Monaco, Thomas J; Davila, Carlos D

    2016-01-01

    Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan.

  14. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension

    PubMed Central

    Monaco, Thomas J; Davila, Carlos D

    2016-01-01

    Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan. PMID:27274200

  15. Timing of cord blood treatment after experimental stroke determines therapeutic efficacy.

    PubMed

    Newcomb, Jennifer D; Ajmo, Craig T; Sanberg, Cyndy D; Sanberg, Paul R; Pennypacker, Keith R; Willing, Alison E

    2006-01-01

    Embolic stroke is thought to cause irreparable damage in the brain immediately adjacent to the region of reduced blood perfusion. Therefore, much of the current research focuses on treatments such as anti-inflammatory, neuroprotective, and cell replacement strategies to minimize behavioral and physiological consequences. In the present study, intravenous delivery of human umbilical cord blood cells (HUCBC) 48 h after a middle cerebral artery occlusion (MCAo) in a rat resulted in both behavioral and physiological recovery. Nissl and TUNEL staining demonstrated that many of the neurons in the core were rescued, indicating that while both necrotic and apoptotic cell death occur in ischemia, it is clear that apoptosis plays a larger role than first anticipated. Further, immunohistochemical and histochemical analysis showed a diminished and/or lack of granulocyte and monocyte infiltration and astrocytic and microglial activation in the parenchyma in animals treated with HUCBC 48 h poststroke. Successful treatment at this time point should offer encouragement to clinicians that a therapy with a broader window of efficacy may soon be available to treat stroke. PMID:16719056

  16. Impact of disease heterogeneity on treatment efficacy of immunotherapy in Type 1 diabetes: different shades of gray.

    PubMed

    Woittiez, Nicky J C; Roep, Bart O

    2015-01-01

    Type 1 diabetes results from selective destruction of insulin-producing pancreatic β-cells by a progressive autoimmune process. Type 1 diabetes proves very heterogeneous in pathology, disease progression and efficacy of therapeutic intervention. Indeed, several immunotherapies that appear ineffective for the entire treated patient population in fact look promising in subgroups of patients. It therefore seems inconceivable that one standard therapy will provide the golden bullet of disease intervention. Instead, personalized medicine may improve immune intervention efficacy rates. We discuss the effect of disease heterogeneity on treatment outcome of immunotherapies, identifying apparent gaps in our understanding of treatment efficacy in subgroups of Type 1 diabetic patients as well as identifying future opportunities for immunotherapy.

  17. Efficacy and environmental acceptability of two ballast water treatment chemicals and an alkylamine based-biocide.

    PubMed

    La Carbona, Stéphanie; Viitasalo-Frösen, Satu; Masson, Daniel; Sassi, Jukka; Pineau, Samuel; Lehtiniemi, Maiju; Corroler, David

    2010-12-15

    Ship's ballast waters transport large numbers of organisms which may become invasive in coastal regions. One option to address this problem is the use of biocides as ballast water treatment (BWT). Efficacy and environmental acceptability of three commercial active substances (the BWT biocides Peraclean(®) Ocean and Seakleen(®), and alkylamine-based biocide Mexel(®) 432/336) were tested against three bacteria species, two vegetative microalgae and one zooplanktonic larva, in 10 and 30 Practical Salinity Unit (PSU) waters. In both salinities, PeraClean(®) Ocean was the most effective biocide against bacteria causing >90% mortality at 20mg/l, compared with 50mg/l for Mexel(®) 432/336 and >500 mg/l for Seakleen(®). Regarding zooplankton, Seakleen(®) was the most effective chemical causing 90% mortality in 24h at concentrations <6 mg/l (LC90(24h)) in both salinities, compared with 23 and 26 mg/l for Mexel(®) 432/336 and 370 and 480 mg/l for PeraClean(®) Ocean in 10 and 30 PSU, respectively. Similar pattern of efficacy was obtained for microalgae in 30 PSU: effective concentrations inducing 50% growth inhibition in 4 days were ≤ 1.6 mg/l for Seakleen(®), ≤ 10.1mg/l for Mexel(®) 432/336 and ≤ 30.9 mg/l for PeraClean(®) Ocean. Our work highlighted that treated waters displayed residual toxicity after 24h still inducing mortality depending on the organism and biocide. However Mexel(®) 432/336 is the only biocide which had no impact on oyster larvae development at effective concentration. Altogether our data showed that Mexel(®) 432/336 was the only biocide displaying a broad spectrum efficacy in concentrations <50mg/l and not toxic for oyster larvae development at this concentration. However residual toxicity of treated waters for any organism should be taken into account in BWT systems utilising biocides. PMID:21056457

  18. Efficacy Projection of Obiltoxaximab for Treatment of Inhalational Anthrax across a Range of Disease Severity

    PubMed Central

    Yamamoto, Brent J.; Shadiack, Annette M.; Carpenter, Sarah; Sanford, Daniel; Henning, Lisa N.; O'Connor, Edward; Gonzales, Nestor; Mondick, John; French, Jonathan; Stark, Gregory V.; Fisher, Alan C.; Casey, Leslie S.

    2016-01-01

    Inhalational anthrax has high mortality even with antibiotic treatment, and antitoxins are now recommended as an adjunct to standard antimicrobial regimens. The efficacy of obiltoxaximab, a monoclonal antibody against anthrax protective antigen (PA), was examined in multiple studies conducted in two animal models of inhalational anthrax. A single intravenous bolus of 1 to 32 mg/kg of body weight obiltoxaximab or placebo was administered to New Zealand White rabbits (two studies) and cynomolgus macaques (4 studies) at disease onset (significant body temperature increase or detection of serum PA) following lethal challenge with aerosolized Bacillus anthracis spores. The primary endpoint was survival. The relationship between efficacy and disease severity, defined by pretreatment bacteremia and toxemia levels, was explored. In rabbits, single doses of 1 to 16 mg/kg obiltoxaximab led to 17 to 93% survival. In two studies, survival following 16 mg/kg obiltoxaximab was 93% and 62% compared to 0% and 0% for placebo (P = 0.0010 and P = 0.0013, respectively). Across four macaque studies, survival was 6.3% to 78.6% following 4 to 32 mg/kg obiltoxaximab. In two macaque studies, 16 mg/kg obiltoxaximab reduced toxemia and led to survival rates of 31%, 35%, and 47% versus 0%, 0%, and 6.3% with placebo (P = 0.0085, P = 0.0053, P = 0.0068). Pretreatment bacteremia and toxemia levels inversely correlated with survival. Overall, obiltox