Effectiveness and Safety of Immunomodulators with Anti-TNF Therapy in Crohn's Disease

PubMed Central

Osterman, Mark T.; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M.; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R.; Lewis, James D.

2015-01-01

Background & Aims The benefit of continuing immunomodulators when “stepping up” to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. Methods We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared using 3 metrics of effectiveness – surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery – and 2 metrics of safety – serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Results Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as “step up” after thiopurine therapy. The rates of surgery (hazard ratio [HR] 1.20, 95% CI 0.73-1.96), hospitalization (HR 0.82 [0.57-1.19]), discontinuation of anti-TNF therapy or surgery (HR 1.09, [0.88-1.34]), and serious infection (HR 0.93 [0.88-1.34]) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risk of opportunistic infection (HR 2.64 [1.21-5.73]) and herpes zoster (HR 3.16 [1.25-7.97]) were increased with combination therapy. Conclusions We found that continuation of immunomodulators after “stepping up” to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. PMID:25724699

Effectiveness and Safety of Immunomodulators With Anti-Tumor Necrosis Factor Therapy in Crohn's Disease.

PubMed

Osterman, Mark T; Haynes, Kevin; Delzell, Elizabeth; Zhang, Jie; Bewtra, Meenakshi; Brensinger, Colleen M; Chen, Lang; Xie, Fenglong; Curtis, Jeffrey R; Lewis, James D

2015-07-01

The benefit of continuing immunomodulators when "stepping up" to anti-tumor necrosis factor (anti-TNF) therapy for Crohn's disease (CD) is uncertain. This study assessed the effectiveness and safety of immunomodulators with anti-TNF therapy in CD. We conducted a retrospective cohort study of new users of anti-TNF therapy for CD in Medicare. Users of anti-TNF combination therapy with immunomodulators were matched to up to 3 users of anti-TNF monotherapy via propensity score and compared by using 3 metrics of effectiveness-surgery, hospitalization, and discontinuation of anti-TNF therapy or surgery-and 2 metrics of safety-serious infection and non-Candida opportunistic infection. Cox regression was used for all analyses. Among new users of infliximab, we matched 381 users of combination therapy to 912 users of monotherapy; among new users of adalimumab, we matched 196 users of combination therapy to 505 users of monotherapy. Combination therapy occurred predominantly as "step up" after thiopurine therapy. The rates of surgery (hazard ratio [HR], 1.20; 95% confidence interval, 0.73-1.96), hospitalization (HR, 0.82; 0.57-1.19), discontinuation of anti-TNF therapy or surgery (HR, 1.09; 0.88-1.34), and serious infection (HR, 0.93; 0.88-1.34) did not differ between users of anti-TNF combination therapy and monotherapy. However, the risks of opportunistic infection (HR, 2.64; 1.21-5.73) and herpes zoster (HR, 3.16; 1.25-7.97) were increased with combination therapy. We found that continuation of immunomodulators after "stepping up" to anti-TNF therapy did not improve outcomes but was associated with an increased risk of opportunistic infection. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Anti-rotavirus effects by combination therapy of stevioside and Sophora flavescens extract.

PubMed

Alfajaro, Mia Madel; Rho, Mun-Chual; Kim, Hyun-Jeong; Park, Jun-Gyu; Kim, Deok-Song; Hosmillo, Myra; Son, Kyu-Yeol; Lee, Ju-Hwan; Park, Sang-Ik; Kang, Mun-Il; Ryu, Young Bae; Park, Ki Hun; Oh, Hyun-Mee; Lee, Seung Woong; Park, Su-Jin; Lee, Woo Song; Cho, Kyoung-Oh

2014-06-01

Anti-rotaviral activities of Sophora flavescens extract (SFE) and stevioside (SV) from Stevia rebaudiana Bertoni either singly or in various combinations were examined in vitro and in vivo using a porcine rotavirus G5[P7] strain. Combination of SFE and SV inhibited in vitro virus replication more efficiently than each single treatment. In the piglet model, SV had no effect on rotavirus enteritis, whereas SFE improved but did not completely cure rotaviral enteritis. Interestingly, combination therapy of SFE and SV alleviated diarrhea, and markedly improved small intestinal lesion score and fecal virus shedding. Acute toxicity tests including the piglet lethal dose 50, and body weight, organ weight and pathological changes for the combination therapy did not show any adverse effect on the piglets. These preliminary data suggest that the combination therapy of SV and SFE is a potential curative medication for rotaviral diarrhea in pigs. Determination of the efficacy of this combination therapy in other species including humans needs to be addressed in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical experience in treating hypertension with fixed-dose combination therapy: angiotensin II receptor blocker losartan plus hydrochlorothiazide.

PubMed

Abe, Masanori; Okada, Kazuyoshi; Matsumoto, Koichi

2009-10-01

The goal of antihypertensive treatment is to reduce cardiovascular and cerebrovascular events associated with high blood pressure. A combination therapy with different antihypertensive agents is more successful than monotherapy in most hypertensive patients, with the added advantage of a better safety profile. Therefore, treatment of hypertensive patients with fixed-dose combination therapy consisting of the angiotensin II receptor blocker losartan along with hydrochlorothiazide (HCTZ) has several potential benefits over monotherapy with each individual component. It provides more effective blood pressure control, a reduction in the likelihood of adverse effects and facilitation of patient compliance due to a simple once-daily regimen. One of the advantages of the combination of losartan with HCTZ is the potential reduction in HCTZ-induced metabolic disorders; in particular, this combination can have attractive benefits for patients of hyperuricemia. Losartan plus HCTZ fixed-dose combination therapy is frequently recommended for the treatment of hypertension and lowers blood pressure in mild-to-moderate and even severe hypertensive patients to a level comparable with other classes of antihypertensive agents in combination with HCTZ. Fixed-dose combination therapy with losartan plus HCTZ is a logical choice as antihypertensive therapy for patients in whom combination therapy is necessary to achieve additional blood pressure reduction.

Combination therapy for erectile dysfunction: an update review.

PubMed

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

2011-05-01

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

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

PubMed Central

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

2018-01-01

BACKGROUND The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations to third-party payer systems, physicians, and patients. OBJECTIVE Develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as first-line therapy in metastatic melanoma while accounting for differential effectiveness in PD-L1 positive and negative patients. METHODS A three-state Markov model (‘PD-L1 positive stable disease’, ‘PD-L1 negative stable disease’, and ‘Progression and/or Death’) was developed using a US societal perspective with a lifetime time horizon of 14.5 years. Transition probabilities were calculated from progression-free survival data reported in the CheckMate-067 trial. Costs were expressed in 2015 US dollars and were determined using national sources. Adverse event (AE) management was determined using immune-related AE (irAE) data from CheckMate-067, irAE management guides for nivolumab and ipilimumab, and treatment guidelines. Utilities were obtained from published literature, using melanoma-specific studies when available, and were weighted based on incidence and duration of irAEs. Base case, one-way sensitivity, and probabilistic sensitivity analyses were conducted. RESULTS Nivolumab-ipilimumab combination therapy is not the cost effective choice ($454,092 per progression-free quality-adjusted-life-year [PFQALY]) compared to nivolumab monotherapy in our base case analysis at a willingness-to-pay threshold of $100,000/PFQALY. Both combination therapy and nivolumab monotherapy were cost-effective choices compared to ipilimumab monotherapy. PD-L1 positive status, utility of nivolumab and combination therapy, and medication costs contributed the most uncertainty to the model. In a population of 100% PD-L1 negative patients, nivolumab was still the optimal treatment but combination therapy had an improved ICER of $295,903/PFQALY. Combination therapy became dominated by nivolumab when 68% of the sample was PD-L1 positive. In addition, the cost of ipilimumab would have to decrease to <$21,555 per dose for combination therapy to have an ICER <$100,000/PFQALY, and to <$19,151 (a 42% reduction) to be more cost-effective than nivolumab monotherapy. CONCLUSIONS Nivolumab-ipilimumab combination therapy is not cost-effective compared to nivolumab monotherapy, which is the most cost-effective option. Professionals in managed care settings should consider the pharmacoeconomic implications of these new immunotherapies as they make value-based formulary decisions and future cost-effectiveness studies are completed. PMID:28530525

Anti-metastatic and pro-apoptotic effects elicited by combination photodynamic therapy with sonodynamic therapy on breast cancer both in vitro and in vivo.

PubMed

Wang, Pan; Li, Caifeng; Wang, Xiaobing; Xiong, Wenli; Feng, Xiaolan; Liu, Quanhong; Leung, Albert Wingnang; Xu, Chuanshan

2015-03-01

Sono-Photodynamic therapy (SPDT), a new modality for cancer treatment, is aimed at enhancing anticancer effects by the combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we investigated the antitumor effect and possible mechanisms of Chlorin e6 (Ce6) mediated SPDT (Ce6-SPDT) on breast cancer both in vitro and in vivo. MTT assay revealed that the combined therapy markedly enhanced cell viability loss of breast cancer cell lines (MDA-MB-231, MCF-7 and 4T1) compared with SDT and PDT alone. Propidium iodide/hoechst33342 double staining reflected that 4T1 cells with apoptotic morphological characteristics were significantly increased in groups given combined therapy. Besides, the combined therapy caused obvious mitochondrial membrane potential (MMP) loss at early 1 h post SPDT treatment. The generation of intracellular reactive oxygen species (ROS) detected by flow cytometry was greatly increased in 4T1 cells treated with the combination therapy, and the loss of cell viability and MMP could be effectively rescued by pre-treatment with the ROS scavenger N-acetylcysteine (NAC). Further, Ce6-SPDT markedly inhibited the tumor growth (volume and weight) and lung metastasis in 4T1 tumor-bearing mice, but had no effect on the body weight. Hematoxylin and eosin staining revealed obvious tissue destruction with large spaces in the Ce6-SPDT groups, and TUNEL staining indicated tumor cell apoptosis after treatment. Immunohistochemistry analysis showed that the expression level of VEGF and MMP were significantly decreased in the combined groups. These results indicated that Ce6-mediated SPDT enhanced the antitumor efficacy on 4T1 cells compared with SDT and PDT alone, loss of MMP and generation of ROS might be involved. In addition, Ce6-mediated SPDT significantly inhibited tumor growth and metastasis in mouse breast cancer 4T1 xenograft model, in which MMP-9 and VEGF may play a crucial role.

Effects of combined fine motor skill and cognitive therapy to cognition, degree of dementia, depression, and activities of daily living in the elderly with Alzheimer's disease.

PubMed

Lee, Jin; Lee, ByoungHee; Park, YuHyung; Kim, Yumi

2015-10-01

[Purpose] This study evaluated the effects of combined fine motor skill and cognitive therapies on cognition, depression, and activities of daily living in elderly patients with Alzheimer's disease (AD). [Subjects and Methods] Twenty-six participants comprised 2 groups. The experimental group (n=13) received combined fine motor skill and cognitive therapy, and the control group (n=13) received only general medical care. [Results] The experimental group showed improvements in cognition, degree of dementia, depression, and activities of daily living compared to the control group. However, there were no significant differences between the two groups. [Conclusion] These results suggest that combined fine motor skill and cognitive therapy improves cognition, degree of dementia, depression, and daily living in elderly patients with AD. These therapies would therefore be effective as general medical care strategies.

Cost-effectiveness of ranibizumab in the treatment of visual impairment due to diabetic macular edema.

PubMed

Haig, Jennifer; Barbeau, Martin; Ferreira, Alberto

2016-07-01

Objective Ranibizumab, an anti-vascular endothelial growth factor designed for ocular use, has been deemed cost-effective in multiple indications by several Health Technology Assessment bodies. This study assessed the cost-effectiveness of ranibizumab monotherapy or combination therapy (ranibizumab plus laser photocoagulation) compared with laser monotherapy for the treatment of visual impairment due to diabetic macular edema (DME). Methods A Markov model was developed in which patients moved between health states defined by best-corrected visual acuity (BCVA) intervals and an absorbing 'death' state. The population of interest was patients with DME due to type 1 or type 2 diabetes mellitus. Baseline characteristics were based on those of participants in the RESTORE study. Main outputs were costs (in 2013 CA$) and health outcomes (in quality-adjusted life-years [QALYs]) and the incremental cost-effectiveness ratio (ICER) was calculated. This cost-utility analysis was conducted from healthcare system and societal perspectives in Quebec. Results From a healthcare system perspective, the ICERs for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$24 494 and CA$36 414 per QALY gained, respectively. The incremental costs per year without legal blindness for ranibizumab monotherapy and combination therapy vs laser monotherapy were CA$15 822 and CA$20 616, respectively. Based on the generally accepted Canadian ICER threshold of CA$50 000 per QALY gained, ranibizumab monotherapy and combination therapy were found to be cost-effective compared with laser monotherapy. From a societal perspective, ranibizumab monotherapy and combination therapy provided greater benefits at lower costs than laser monotherapy (ranibizumab therapy dominated laser therapy). Conclusions Ranibizumab monotherapy and combination therapy resulted in increased quality-adjusted survival and time without legal blindness and lower costs from a societal perspective compared with laser monotherapy.

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

PubMed

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

2017-11-25

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

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

PubMed

Ge, Yanxiu; Ma, Yakun; Li, Lingbing

2016-10-01

Single drug therapy that leads to the multidrug resistance of cancer cells and severe side-effect is a thing of the past. Combination therapies that affect multiple signaling pathways have been the focus of recent active research. Due to the successful development of prodrug-based nano-drug delivery systems (P-N-DDSs), their use has been extended to combination therapy as drug delivery platforms. In this review, we focus specifically on the P-N-DDSs in the field of combination therapy including the combinations of prodrugs with different chemotherapeutic agents, other therapeutic agents, nucleic acid or the combination of different types of therapy (e.g. chemotherapy and phototherapy). The relevant examples of prodrug-based nanoparticulate drug delivery strategy in combination cancer therapy from the recent literature are discussed to demonstrate the feasibilities of relevant technology. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study

PubMed Central

Abdul-Ghani, Muhammad; Migahid, Osama; Megahed, Ayman; Adams, John; Triplitt, Curtis; DeFronzo, Ralph A.; Zirie, Mahmoud; Jayyousi, Amin

2017-01-01

OBJECTIVE The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea. RESEARCH DESIGN AND METHODS The study randomized 231 patients with poorly controlled (HbA1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1) pioglitazone plus weekly exenatide (combination therapy) or 2) basal plus prandial insulin (insulin therapy) to maintain HbA1c <7.0% (53 mmol/mol). RESULTS After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA1c from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA1c independent of sex, ethnicity, BMI, or baseline HbA1c. Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group. CONCLUSIONS Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea. PMID:28096223

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

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

Li, Xiaofei; Zhu, Yanshuang; He, Huabin

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

[Play therapy--psychotherapy with play as the medium: II. New developments].

PubMed

von Gontard, Alexander; Lehmkuhl, Gerd

2003-02-01

A wide array of new forms and combinations of play therapy have been developed. The aim of the second part of this paper is to present an overview of these newer approaches, including: focussed therapies for specific disorders; behavioural approaches like the Cognitive-Behavioral Play Therapy and the Parent-Child Interaction Therapy; various combinations with family therapy; and therapies especially for preschool children like Filial Therapy, Developmental Play Therapy and Thera-play. Following a phase of experiments and combinations, the empirical evaluation of many play-therapy forms is needed. Especially questions of the differential indication of specific play-therapies and their effectiveness in the therapeutical practice need to be studied.

Combination therapy for solar lentigines.

PubMed

Farris, Patricia K

2004-01-01

Solar lentigines are benign, hyperpigmented lesions that present a significant cosmetic nuisance for many middle-aged and elderly patients with chronic accumulated sun exposure. While previous monotherapies designed to lighten these lesions offer relatively modest improvement, there are several new treatment options. Combination topical therapy using 2% mequinol/0.01% tretinoin [Solagé Topical Solution] has been shown to markedly reduce lesion darkness with few side effects. Chemical peels can give good results either alone or in combination with topical therapy. Cryotherapy is an effective and inexpensive way of treating solar lentigines while IPL and lasers are more costly treatment options. For patients desiring treatment, optimal cosmetic improvement can be achieved using a combination of topical and procedural therapies.

[Clinical study on a concomitant therapy with fluconazole and human recombinant granulocyte colony stimulating factor in the treatment of systemic fungal infections with hematological disorders].

PubMed

Kitamura, K; Miyagawa, K; Urabe, A; Sato, H; Obayashi, Y; Aoki, I; Takaku, F; Togawa, A; Shindou, E; Wakabayashi, Y; Ohshima, T; Horikoshi, A; Nomura, T; Ohki, I; Suzuki, K; Kamakura, M; Oguchi, A; Toyama, K; Yaguchi, M; Aoki, N; Kato, A; Mizoguchi, H; Masuda, M; Irie, S; Fujioka, S

1996-12-01

The clinical efficacy and the safety of concomitant therapy with fluconazole and recombinant human granulocyte colony stimulating factor (rhG-CSF) was compared with fluconazole monotherapy in neutropenic patients with hematological disorders. The clinical efficacy rate was 73.5% (25/34) in the combination therapy and 48.1% (37/77) in monotherapy. The difference between the two is statistically significant. Side effects were not observed in the combination group, but laboratory abnormalities were found in 6 patients with an incident rate of 11%. The combination therapy with fluconazole and rhG-CSF may be selected as empiric therapy for systemic fungal infection associated with hematological disorders, since this combination therapy showed high efficacy and low incident of side effects. Some patients, however, did not show increased neutrophil counts in spite of rhG-CSF administration.

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study.

PubMed

Hong, Su Jin; Park, Soo-Heon; Moon, Jeong Seop; Shin, Woon Geon; Kim, Jae Gyu; Lee, Yong Chan; Lee, Dong Ho; Jang, Jae Young; Kim, Jae J; Lee, Hang-Lak; Lee, Sang Woo; Hwangbo, Young; Xu, Jianming; Wang, Bangmao; Xue, Zhanxiong; Liu, Fei; Yuan, Yaozong; Leelakusolvong, Somchai; Dy, Frederick

2016-11-15

To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. The mean decreases in the total symptom score at 4 weeks were estimated to be -18.1±13.8 in the combination therapy group and -15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were -8.4±6.6 in the combination therapy group and -6.8±5.9 in the monotherapy group (p=0.009). Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy.

Combination therapeutics of Nilotinib and radiation in acute lymphoblastic leukemia as an effective method against drug-resistance.

PubMed

Kaveh, Kamran; Takahashi, Yutaka; Farrar, Michael A; Storme, Guy; Guido, Marcucci; Piepenburg, Jamie; Penning, Jackson; Foo, Jasmine; Leder, Kevin Z; Hui, Susanta K

2017-07-01

Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is characterized by a very poor prognosis and a high likelihood of acquired chemo-resistance. Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL patients relapse following treatment with TKI due to the development of resistance. We developed an in vitro model of Nilotinib-resistant Ph+ leukemia cells to investigate whether low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance. Additionally, we developed a mathematical model, parameterized by cell viability experiments under Nilotinib treatment and LDR, to explain the cellular response to combination therapy. The addition of LDR significantly reduced drug resistance both in vitro and in computational model. Decreased expression level of phosphorylated AKT suggests that the combination treatment plays an important role in overcoming resistance through the AKT pathway. Model-predicted cellular responses to the combined therapy provide good agreement with experimental results. Augmentation of LDR and Nilotinib therapy seems to be beneficial to control Ph+ leukemia resistance and the quantitative model can determine optimal dosing schedule to enhance the effectiveness of the combination therapy.

Role of zoledronic acid in oncolytic virotherapy: Promotion of antitumor effect and prevention of bone destruction.

PubMed

Yamakawa, Yasuaki; Tazawa, Hiroshi; Hasei, Joe; Osaki, Shuhei; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Uotani, Kouji; Fujiwara, Tomohiro; Yoshida, Aki; Kunisada, Toshiyuki; Urata, Yasuo; Kagawa, Shunsuke; Ozaki, Toshifumi; Fujiwara, Toshiyoshi

2017-09-01

Osteosarcoma is an aggressive malignant bone tumor that causes bone destruction. Although tumor-specific replicating oncolytic adenovirus OBP-301 induces an antitumor effect in an osteosarcoma tumor, it cannot prevent bone destruction. Zoledronic acid (ZOL) is a clinically available agent that inhibits bone destruction. In this study, we investigated the potential of combination therapy with OBP-301 and ZOL against osteosarcomas with bone destruction. The antitumor activity of OBP-301 and ZOL in monotherapy or combination therapy was assessed using three human osteosarcoma cell lines (143B, MNNG/HOS, SaOS-2). The cytotoxic effect of OBP-301 and/or ZOL was measured by assay of cell apoptosis. The effect of OBP-301 and ZOL on osteoclast activation was investigated. The potential of combination therapy against tumor growth and bone destruction was analyzed using an orthotopic 143B osteosarcoma xenograft tumor model. OBP-301 and ZOL decreased the viability of human osteosarcoma cells. Combination therapy with OBP-301 and ZOL displayed a synergistic antitumor effect, in which OBP-301 promoted apoptosis through suppression of anti-apoptotic myeloid cell leukemia 1 (MCL1). Combination therapy significantly inhibited tumor-mediated osteoclast activation, tumor growth and bone destruction compared to monotherapy. These results suggest that combination therapy of OBP-301 and ZOL suppresses osteosarcoma progression via suppression of MCL1 and osteoclast activation. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

PubMed

Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

2018-05-01

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD.

PubMed

Li, Li; Yang, Li; Zhuo, Chuan-jun; Wang, Yu-Feng

2013-08-22

To evaluate the efficacy of combined methylphenidate and EEG feedback treatment for children with ADHD. Forty patients with ADHD were randomly assigned to the combination group (methylphenidate therapy and EEG feedback training) or control group (methylphenidate therapy and non-feedback attention training) in a 1:1 ratio using the double-blind method. These patients, who met the DSM-IV diagnostic criteria and were aged between 7 and 16 years, had obtained optimal therapeutic effects by titrating the methylphenidate dose prior to the trial. The patients were assessed using multiple parameters at baseline, after 20 treatment sessions, after 40 treatment sessions, and in 6-month follow-up studies. Compared to the control group, patients in the combination group had reduced ADHD symptoms and improved in related behavioural and brain functions. The combination of EEG feedback and methylphenidate treatment is more effective than methylphenidate alone. The combined therapy is especially suitable for children and adolescents with ADHD who insufficiently respond to single drug treatment or experience drug side effects.

Enhanced effects by 4-phenylbutyrate in combination with RTK inhibitors on proliferation in brain tumor cell models

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

Marino, Ana-Maria; Center for Molecular Medicine CMM, Karolinska University Hospital, Stockholm; Sofiadis, Anastasios

2011-07-22

Highlights: {yields} The histone deacetylase inhibitor 4-phenylbutyrate substantially enhance efficacy of the receptor tyrosine kinase inhibitors gefitinib or vandetanib in glioma and medulloblastoma cell lines. {yields} Cell death increases and clonogenic survival is reduced in the combination treatments, over mono-therapy. {yields} Combination treatments with these drugs may improve clinical outcome for cancer therapy. -- Abstract: We have investigated in vitro effects of anticancer therapy with the histone deacetylase inhibitor (HDACi) 4-phenylbutyrate (4-PB) combined with receptor tyrosine kinase inhibitors (RTKi) gefitinib or vandetanib on the survival of glioblastoma (U343MGa) and medulloblastoma (D324Med) cells. In comparison with individual effects of these drugs,more » combined treatment with gefitinib/4-PB or vandetanib/4-PB resulted in enhanced cell killing and reduced clonogenic survival in both cell lines. Our results suggest that combined treatment using HDACi and RTKi may beneficially affect the outcome of cancer therapy.« less

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

PubMed Central

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

2015-01-01

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

Accelerating cancer therapy development: the importance of combination strategies and collaboration. Summary of an Institute of Medicine workshop.

PubMed

LoRusso, Patricia M; Canetta, Renzo; Wagner, John A; Balogh, Erin P; Nass, Sharyl J; Boerner, Scott A; Hohneker, John

2012-11-15

Cancer cells contain multiple genetic changes in cell signaling pathways that drive abnormal cell survival, proliferation, invasion, and metastasis. Unfortunately, patients treated with single agents inhibiting only one of these pathways--even if showing an initial response--often develop resistance with subsequent relapse or progression of their cancer, typically via the activation of an alternative uninhibited pathway. Combination therapies offer the potential for inhibiting multiple targets and pathways simultaneously to more effectively kill cancer cells and prevent or delay the emergence of drug resistance. However, there are many unique challenges to developing combination therapies, including devising and applying appropriate preclinical tests and clinical trial designs, prioritizing which combination therapies to test, avoiding overlapping toxicity of multiple agents, and overcoming legal, cultural, and regulatory barriers that impede collaboration among multiple companies, organizations, and/or institutions. More effective strategies to efficiently develop combination cancer therapies are urgently needed. Thus, the Institute of Medicine's National Cancer Policy Forum recently convened a workshop with the goal of identifying barriers that may be impeding the development of combination investigational cancer therapies, as well as potential solutions to overcome those barriers, improve collaboration, and ultimately accelerate the development of promising combinations of investigational cancer therapies. ©2012 AACR.

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial.

PubMed

Ueda, Tamenobu; Kai, Hisashi; Imaizumi, Tsutomu

2012-07-01

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50 mg losartan and 12.5 mg HCTZ (n=109) or a high-dose therapy with 100 mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5 mm Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6 mm Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1 mm Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2 mm Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.

[Acupuncture combined with magnetic therapy for treatment of temple-jaw joint dysfunction].

PubMed

Wang, Xiao-Hui; Zhang, Wen

2009-04-01

To compare clinical therapeutic effects of acupuncture combined with magnetic therapy and simple magnetic therapy on temple-jaw joint dysfunction. Eighty-two cases were randomly divided into an observation group (n = 52) and a control group (n = 30). The observation group was treated with acupuncture at Xiaguan (ST 7), Jiache (ST 6), Hegu (LI 4), etc. and AL-2 low frequency electromagnetic comprehensive treatment instrument; the control group was treated with AL-2 low frequency electromagnetic comprehensive treatment instrument. The cured and markedly effective rate of 90.4% in the observation group was significantly better than 66.7% in the control group (P < 0.01), and the total effective rate of 98.1% in the observation group was significantly better than 86.7% in the control group (P < 0.05). The therapeutic effect of acupuncture combined with magnetic therapy is significantly better than that of the simple magnetic therapy on temple-jaw joint dysfunction.

Combination Therapy for Treatment of Infections with Gram-Negative Bacteria

PubMed Central

Cosgrove, Sara E.; Maragakis, Lisa L.

2012-01-01

Summary: Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria. PMID:22763634

Functional exercise in combination with auricular plaster therapy is more conducive to rehabilitation of menopausal women patients with anxiety disorder

PubMed Central

Han, Yubin; Duan, Fugui; Xu, Rongmei; Wang, Yi; Zhang, Hongyu

2015-01-01

Objective: Observe the effect of functional exercise in combination with auricular plaster therapy on menopausal women patients with anxiety disorder. Method: Select 45 menopausal women patients with anxiety disorder and then adopt random digital table to divide them into a functional exercise group, an auricular plaster therapy group and a combination group. Each group consists of 15 patients. The patients in the functional exercise group do yoga exercise twice a day; those in the auricular plaster therapy group are provided with the auricular plaster therapy twice a day; those in the combination group do yoga exercise and then they are provided with the auricular plaster therapy twice a day. Before the treatment and after 12 weeks’ treatment, respectively detect and compare the selected patients in the three groups in respect HAMA score, physical function score and mental function score; And the cured patients are followed up for 3 months to compare recurrence rate of each group. Results: After 12 weeks’ treatment, HAMA score, physical function score and mental function score of the combination group are obviously better than those of another two groups (P<0.05); Of the cure rate and the recurrence rate within 3 months, the cure rate of the combination group is higher and the recurrence rate is low. Conclusion: Through the functional rehabilitation exercise in combination with the auricular plaster, the combined curative effect is obviously better than that of single treatment and the clinical recurrence rate is significantly lower than that of single treatment. It shows that the combined treatment method presents obvious synergistic effect and the synergistic treatment is more beneficial to improve the curative effect. PMID:26885051

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

PubMed

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

2002-12-01

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

Rectal cancer. Treatment advances that reduce recurrence rates and lengthen survival.

PubMed

Sexe, R; Miedema, B W

1993-07-01

The risk of malignant disease arising in rectal mucosa is high. Surgery is the most effective form of treatment but results in cure in only 50% of patients. Adjuvant preoperative radiation therapy reduces the likelihood of local recurrence but does not improve survival rates. Fluorouracil is the most effective agent for adjuvant chemotherapy and slightly improves survival when given after surgery. Combining radiation therapy with chemotherapy appears to have a synergistic effect, and recent studies show that providing this combination after surgery improves survival. Future trends in the treatment of rectal cancer are expected to include expanded use of local excision to preserve anal sphincter function, preoperative use of a combination of radiation therapy and chemotherapy, perioperative use of chemotherapy combined with immunostimulating therapy, and use of tumor antibodies for diagnostic and therapeutic purposes.

Optimal control of malaria: combining vector interventions and drug therapies.

PubMed

Khamis, Doran; El Mouden, Claire; Kura, Klodeta; Bonsall, Michael B

2018-04-24

The sterile insect technique and transgenic equivalents are considered promising tools for controlling vector-borne disease in an age of increasing insecticide and drug-resistance. Combining vector interventions with artemisinin-based therapies may achieve the twin goals of suppressing malaria endemicity while managing artemisinin resistance. While the cost-effectiveness of these controls has been investigated independently, their combined usage has not been dynamically optimized in response to ecological and epidemiological processes. An optimal control framework based on coupled models of mosquito population dynamics and malaria epidemiology is used to investigate the cost-effectiveness of combining vector control with drug therapies in homogeneous environments with and without vector migration. The costs of endemic malaria are weighed against the costs of administering artemisinin therapies and releasing modified mosquitoes using various cost structures. Larval density dependence is shown to reduce the cost-effectiveness of conventional sterile insect releases compared with transgenic mosquitoes with a late-acting lethal gene. Using drug treatments can reduce the critical vector control release ratio necessary to cause disease fadeout. Combining vector control and drug therapies is the most effective and efficient use of resources, and using optimized implementation strategies can substantially reduce costs.

Combination therapy with clomiphene citrate and anastrozole is a safe and effective alternative for hypoandrogenic subfertile men.

PubMed

Alder, Nathan J; Keihani, Sorena; Stoddard, Gregory J; Myers, Jeremy B; Hotaling, James M

2018-06-06

To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow-ups. Treatment side effects were recorded; prostatic-specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t-test and Wilcoxon's signed-rank test. A total of 51 men were included, with a mean age of 35.4 ± 7.4 years and a mean body mass index of 35.0 ± 8.0 kg/m 2 . After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Two drugs are better than one. A short history of combined therapy of ovarian cancer.

PubMed

Bukowska, Barbara; Gajek, Arkadiusz; Marczak, Agnieszka

2015-01-01

Combined therapy of ovarian cancer has a long history. It has been applied for many years. The first drug which was commonly combined with other chemotherapeutics was cisplatin. It turned out to be effective given together with alkylating agents as well as with taxanes. Another drug which is often the basis of first-line therapy is doxorubicin. The use of traditional chemotherapy is often limited due to side effects. This is why new drugs, targeted specifically at cancer cells (e.g. monoclonal antibodies or epidermal growth factor receptor inhibitors), offer a welcome addition when used in combination with conventional anticancer agents. Drugs applied in combination should be synergistic or at least additive. To evaluate the type of interaction between drugs in a plausible sequence, isobolographic analysis is used. This method allows one to assess whether the two agents could make an efficient combination, which might improve the therapy of ovarian cancer.

Complementary Effects of Negative-Pressure Wound Therapy and Pulsed Radiofrequency Energy on Cutaneous Wound Healing in Diabetic Mice.

PubMed

Chen, Bin; Kao, Huang-Kai; Dong, Ziqing; Jiang, Zhaohua; Guo, Lifei

2017-01-01

Negative-pressure wound therapy and pulsed radiofrequency energy are two clinical modalities used to treat soft-tissue wounds. They are purported to affect healing differently. The aim of this experimental study was to contrast the two modalities at a mechanistic level and to investigate whether their combined therapy could achieve additive and complementary effects on wound healing. Full-thickness dorsal cutaneous wounds of diabetic, db/db, mice were treated with either negative-pressure wound therapy, pulsed radiofrequency energy, or combined therapies. Macroscopic healing kinetics were examined. Epidermal regeneration (proliferation rate and length of reepithelialization) and neovascularization (blood vessel density) were investigated. Messenger RNA levels indicative of angiogenic (basic fibroblast growth factor), profibrotic (transforming growth factor-β), epidermal proliferative (keratinocyte growth factor), and extracellular matrix remodeling (collagen 1) processes were measured in wound tissues. All three treatment groups displayed faster wound healing. The negative-pressure wound therapy/pulsed radiofrequency energy combined therapy led to significantly faster healing than either the negative-pressure wound therapy or pulsed radiofrequency energy therapy alone. Epidermal regeneration and neovascularization were enhanced in all three groups. The two negative-pressure wound therapy groups (alone and combined with pulsed radiofrequency energy) demonstrated more significant increases in expression of all assayed growth factors than the pulsed radiofrequency energy group. Furthermore, the combined therapy exhibited a more profound elevation in collagen 1 expression than either of the two therapies alone. Combining the negative-pressure wound therapy and pulsed radiofrequency energy modalities can achieve additive benefits in cutaneous healing, and the two therapies can be easily used together to complement each other in clinical wound treatments.

He-Ne ILLLI used for brain trauma: a clinical observation of 46 cases

NASA Astrophysics Data System (ADS)

Yang, Da-Ke; Ru, Zheng-Guo; Ge, Sheng-Li; Shuo, Wei-Lan

1998-11-01

With the background that ILLLI can lower the viscosity of blood, improve the microcirculation, we investigated and compared the therapeutic effect of conventional drug therapy and ILLLI combined drug therapy for brain trauma. We found that ILLLI combined drug therapy could effectively alleviate some symptoms such as headache, vertigo, nausea, vomiting, blurred vision, anorexia caused by brain trauma. the therapeutic effect of treated group was prior to control group.

Metformin and pioglitazone combination therapy ameliorate polycystic ovary syndrome through AMPK/PI3K/JNK pathway

PubMed Central

Wu, Yuanyuan; Li, Pengfen; Zhang, Dan; Sun, Yingpu

2018-01-01

Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder, which results in health problems such as menstrual disorders, hyperandrogenism and persistent anovulation. Hyperandrogenism and insulin resistance are the basic characteristics of PCOS. To investigate the combined effect of metformin and pioglitazone on POCS and the potential mechanisms, a rat model of PCOS was established by intramuscular injection of estradiol valerate (EV). The effect of metformin and pioglitazone monotherapy or combination therapy in control rats and PCOS rats was evaluated, involving the testosterone level, follicular development and insulin resistance. The potential mechanism for the therapeutic effect of metformin and pioglitazone on POCS was explored through using three inhibitors of the 5′adenosine monophosphate-activated protein kinase (AMPK)/phosphoinositide-3 kinase (PI3K)/c-Jun N-terminal kinase (JNK) pathway (Compound C, Wortmannin and SP600125). The results showed that EV-induced PCOS rats demonstrated hyperandrogenemia, hyperinsulinemia and follicular dysplasia. Metformin or pioglitazone monotherapy significantly suppressed the high level of testosterone, reduced the raised percentage of cystic follicles and primary follicles, promoted the number of early antral follicles, and markedly decreased the high concentration of fasting insulin and homeostatic model assessment for insulin resistance index in PCOS rats. In addition, metformin and pioglitazone combination therapy demonstrated greater efficacy than its individual components. Furthermore, individual or joint treatment with metformin and pioglitazone affected the phosphorylation level of JNK in PCOS rats. Compound C and Wortmannin eliminated the effect of metformin and pioglitazone combination therapy on improving the follicular growth in PCOS rats, whereas SP600125 treatment enhanced this combination therapy effect. These data suggested that metformin and pioglitazone combination therapy demonstrated great efficacy in ameliorating PCOS through regulating the AMPK/PI3K/JNK pathway. PMID:29434814

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

The application of hyaluronic acid-derivatized carbon nanotubes in hematoporphyrin monomethyl ether-based photodynamic therapy for in vivo and in vitro cancer treatment

PubMed Central

Shi, Jinjin; Ma, Rourou; Wang, Lei; Zhang, Jing; Liu, Ruiyuan; Li, Lulu; Liu, Yan; Hou, Lin; Yu, Xiaoyuan; Gao, Jun; Zhang, Zhenzhong

2013-01-01

Carbon nanotubes (CNTs) have shown great potential in both photothermal therapy and drug delivery. In this study, a CNT derivative, hyaluronic acid-derivatized CNTs (HA-CNTs) with high aqueous solubility, neutral pH, and tumor-targeting activity, were synthesized and characterized, and then a new photodynamic therapy agent, hematoporphyrin monomethyl ether (HMME), was adsorbed onto the functionalized CNTs to develop HMME-HA-CNTs. Tumor growth inhibition was investigated both in vivo and in vitro by a combination of photothermal therapy and photodynamic therapy using HMME-HA-CNTs. The ability of HMME-HA-CNT nanoparticles to combine local specific photodynamic therapy with external near-infrared photothermal therapy significantly improved the therapeutic efficacy of cancer treatment. Compared with photodynamic therapy or photothermal therapy alone, the combined treatment demonstrated a synergistic effect, resulting in higher therapeutic efficacy without obvious toxic effects to normal organs. Overall, it was demonstrated that HMME-HA-CNTs could be successfully applied to photodynamic therapy and photothermal therapy simultaneously in future tumor therapy. PMID:23843694

Traditional manual acupuncture combined with rehabilitation therapy for shoulder hand syndrome after stroke within the Chinese healthcare system: a systematic review and meta-analysis.

PubMed

Peng, Le; Zhang, Chao; Zhou, Lan; Zuo, Hong-Xia; He, Xiao-Kuo; Niu, Yu-Ming

2018-04-01

To investigate the effectiveness of traditional manual acupuncture combined with rehabilitation therapy versus rehabilitation therapy alone for shoulder hand syndrome after stroke. PubMed, EMBASE, the Cochrane Library, Chinese Biomedicine Database, China National Knowledge Infrastructure, VIP Information Database, Wan Fang Database and reference lists of the eligible studies were searched up to July 2017 for relevant studies. Randomized controlled trials that compared the combined effects of traditional manual acupuncture and rehabilitation therapy to rehabilitation therapy alone for shoulder hand syndrome after stroke were included. Two reviewers independently screened the searched records, extracted the data and assessed risk of bias of the included studies. The treatment effect sizes were pooled in a meta-analysis using RevMan 5.3 software. A total of 20 studies involving 1918 participants were included in this study. Compared to rehabilitation therapy alone, the combined therapy significantly reduced pain on the visual analogue scale and improved limb movement on the Fugl-Meyer Assessment scale and the performance of activities of daily living (ADL) on the Barthel Index scale or Modified Barthel Index scale. Of these, the visual analogue scale score changes were significantly higher (mean difference = 1.49, 95% confidence interval = 1.15-1.82, P < 0.00001) favoring the combined therapy after treatment, with severe heterogeneity ( I 2  = 71%, P = 0.0005). Current evidence suggests that traditional manual acupuncture integrated with rehabilitation therapy is more effective in alleviating pain, improving limb movement and ADL. However, considering the relatively low quality of available evidence, further rigorously designed and large-scale randomized controlled trials are needed to confirm the results.

Interdependent IL-7 and IFN-γ signalling in T-cell controls tumour eradication by combined α-CTLA-4+α-PD-1 therapy

PubMed Central

Shi, Lewis Zhichang; Fu, Tihui; Guan, Baoxiang; Chen, Jianfeng; Blando, Jorge M.; Allison, James P.; Xiong, Liangwen; Subudhi, Sumit K.; Gao, Jianjun; Sharma, Padmanee

2016-01-01

Combination therapy with α-CTLA-4 and α-PD-1 has shown significant clinical responses in different types of cancer. However, the underlying mechanisms remain elusive. Here, combining detailed analysis of human tumour samples with preclinical tumour models, we report that concomitant blockade of CTLA-4 and PD-1 improves anti-tumour immune responses and synergistically eradicates tumour. Mechanistically, combination therapy relies on the interdependence between IL-7 and IFN-γ signalling in T cells, as lack of either pathway abrogates the immune-boosting and therapeutic effects of combination therapy. Combination treatment increases IL-7Rα expression on tumour-infiltrating T cells in an IFN-γ/IFN-γR signalling-dependent manner, which may serve as a potential biomarker for clinical trials with immune checkpoint blockade. Our data suggest that combining immune checkpoint blockade with IL-7 signalling could be an effective modality to improve immunotherapeutic efficacy. Taken together, we conclude that combination therapy potently reverses immunosuppression and eradicates tumours via an intricate interplay between IFN-γ/IFN-γR and IL-7/IL-7R pathways. PMID:27498556

Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice.

PubMed

Diniz, Lívia de Figueiredo; Mazzeti, Ana Lia; Caldas, Ivo Santana; Ribeiro, Isabela; Bahia, Maria Terezinha

2018-06-01

Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using Trypanosoma cruzi strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant T. cruzi strain. After exclusion of antagonistic effects using in vitro assays, infected mice were treated with E1224 and benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and benznidazole against murine T. cruzi infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies. Copyright © 2018 Diniz et al.

Outcome of E1224-Benznidazole Combination Treatment for Infection with a Multidrug-Resistant Trypanosoma cruzi Strain in Mice

PubMed Central

Mazzeti, Ana Lia; Caldas, Ivo Santana; Ribeiro, Isabela; Bahia, Maria Terezinha

2018-01-01

ABSTRACT Combination therapy has been proposed as an alternative therapeutic approach for the treatment of Chagas disease. In this study, we evaluated the effect of treatment with benznidazole combined with E1224 (ravuconazole prodrug) in an experimental murine model of acute infection. The first set of experiments assessed the range of E1224 doses required to induce parasitological cure using Trypanosoma cruzi strains with different susceptibilities to benznidazole (Y and Colombian). All E1224 doses were effective in suppressing the parasitemia and preventing death; however, parasitological cure was observed only in mice infected with Y strain. Considering these results, we evaluated the effect of combined treatment against Colombian, a multidrug-resistant T. cruzi strain. After exclusion of antagonistic effects using in vitro assays, infected mice were treated with E1224 and benznidazole in monotherapy or in combination at day 4 or 10 postinoculation. All treatments were well tolerated and effective in suppressing parasitemia; however, parasitological and PCR assays indicated no cure among mice treated with monotherapies. Intriguingly, the outcome of combination therapy was dependent on treatment onset. Early treatment using optimal doses of E1224-benznidazole induced a 100% cure rate, but this association could not eliminate a well-established infection. The beneficial effect of combination therapy was evidenced by further reductions of the patent parasitemia period in the group receiving combined therapy compared with monotherapies. Our results demonstrated a positive interaction between E1224 and benznidazole against murine T. cruzi infection using a multidrug-resistant strain and highlighted the importance of a stringent experimental model in the evaluation of new therapies. PMID:29555633

[The optimization of an early rehabilitation program for cerebral stroke patients: the use of different methods of magneto- and laser therapy].

PubMed

Kochetkov, A V; Gorbunov, F E; Minenkov, A A; Strel'tsova, E N; Filina, T F; Krupennikov, A I

2000-01-01

Magnetotherapy and laser therapy were used in complex and complex-combined regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on the poststroke week 4-5. Clinico-neurologic, neurophysiological and cerebrohemodynamic findings evidence for the highest effectiveness of neurorehabilitation including complex magneto-laser therapy in hemispheric ischemic and hemorrhagic stroke of subcortical location in the absence of marked clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined magneto-laser therapy is more effective for correction of spastic dystonia. Mutual potentiation of magnetotherapy and laser therapy results in maximal development of collateral circulation and cerebral hemodynamic reserve (84% of the patients). Complex effects manifest in arteriodilating and venotonic effects. Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia and hyperfibrinogenemia.

The Benefits of Combination Therapy with Esomeprazole and Rebamipide in Symptom Improvement in Reflux Esophagitis: An International Multicenter Study

PubMed Central

Hong, Su Jin; Park, Soo-Heon; Moon, Jeong Seop; Shin, Woon Geon; Kim, Jae Gyu; Lee, Yong Chan; Lee, Dong Ho; Jang, Jae Young; Kim, Jae J.; Lee, Hang-Lak; Lee, Sang Woo; Hwangbo, Young; Xu, Jianming; Wang, Bangmao; Xue, Zhanxiong; Liu, Fei; Yuan, Yaozong; Leelakusolvong, Somchai; Dy, Frederick

2016-01-01

Background/Aims To investigate the effects of esomeprazole and rebamipide combination therapy on symptomatic improvement in patients with reflux esophagitis. Methods A total of 501 patients with reflux esophagitis were randomized into one of the following two treatment regimens: 40 mg esomeprazole plus 300 mg rebamipide daily (combination therapy group) or 40 mg esomeprazole daily (monotherapy group). We used a symptom questionnaire that evaluated heartburn, acid regurgitation, and four upper gastrointestinal symptoms. The primary efficacy end point was the mean decrease in the total symptom score. Results The mean decreases in the total symptom score at 4 weeks were estimated to be −18.1±13.8 in the combination therapy group and −15.1±11.9 in the monotherapy group (p=0.011). Changes in reflux symptoms from baseline after 4 weeks of treatment were −8.4±6.6 in the combination therapy group and −6.8±5.9 in the monotherapy group (p=0.009). Conclusions Over a 4-week treatment course, esomeprazole and rebamipide combination therapy was more effective in decreasing the symptoms of reflux esophagitis than esomeprazole monotherapy. PMID:27282265

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

PubMed

Fujikawa, Keita; Hasebe, Naoyuki; Kikuchi, Kenjiro

2005-07-01

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

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study.

PubMed

Lim, Yoo Li; Kim, Moon Young; Jang, Yoon Ok; Baik, Soon Koo; Kwon, Sang Ok

2017-09-15

Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response. Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. Combination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.

Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

PubMed

Zhang, Ming; Tao, Tao; Zhang, Zhao-Bo; Zhu, Xiao; Fan, Wen-Guo; Pu, Li-Jun; Chu, Lei; Yue, Shou-Wei

2016-03-01

To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. Prospective randomized controlled study. Department of physical medicine and rehabilitation. Patients with dysphagia with medullary infarction (N=82). Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with medullary infarction. A sensory approach appears to be better than a motor approach. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis.

PubMed

Talamo Guevara, Maria; McColley, Susanna A

2017-11-01

Lumacaftor-ivacaftor is indicated for treatment of cystic fibrosis (CF) in patients homozygous for the Phe-508del cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. In clinical trials, treated patients showed improved pulmonary function, reduced pulmonary exacerbations, and other benefits. This article reviews safety of this therapy. Areas covered: Safety findings in ivacaftor, lumacaftor and combined therapy trials, and reported subsequently through post-approval evaluation, were accessed by PubMed and Google searches using key words 'VX-770', 'ivacaftor', 'VX-809', and 'lumacaftor'. Transaminitis was seen in ivacaftor and combination trials. Non-congenital cataracts were seen in pre-clinical animal studies and in children taking ivacaftor and combined therapy. Dyspnea occurs in some patients taking lumacaftor and combined therapy and usually resolves without stopping treatment. Lumacaftor is a strong inducer of CYP3A while ivacaftor is a CYP3A sensitive substrate. Combination therapy can decrease systemic exposure of medications that are substrates of CYP3A, decreasing therapeutic effect. Co-administration of lumacaftor-ivacaftor with sensitive CYP3A substrates or CYP3A substrates with narrow therapeutic index is not recommended. Expert opinion: Lumacaftor-ivacaftor therapy may be associated with ocular and hepatic side effects. Specific recommendations for monitoring are available. Dyspnea occurs, especially during initiation of treatment. Potential drug interactions should be evaluated in patients taking combination therapy. The risk benefit ratio of lumacaftor-ivacaftor favors therapy.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies. PMID:21453539

Combination cell therapy with mesenchymal stem cells and neural stem cells for brain stroke in rats.

PubMed

Hosseini, Seyed Mojtaba; Farahmandnia, Mohammad; Razi, Zahra; Delavari, Somayeh; Shakibajahromi, Benafsheh; Sarvestani, Fatemeh Sabet; Kazemi, Sepehr; Semsar, Maryam

2015-05-01

Brain stroke is the second most important events that lead to disability and morbidity these days. Although, stroke is important, there is no treatment for curing this problem. Nowadays, cell therapy has opened a new window for treating central nervous system disease. In some previous studies the Mesenchymal stem cells and neural stem cells. In this study, we have designed an experiment to assess the combination cell therapy (Mesenchymal and Neural stem cells) effects on brain stroke. The Mesenchymal stem cells were isolated from adult rat bone marrow and the neural stem cells were isolated from ganglion eminence of rat embryo 14 days. The Mesenchymal stem cells were injected 1 day after middle cerebral artery occlusion (MCAO) and the neural stem cells transplanted 7 day after MCAO. After 28 days, the neurological outcomes and brain lesion volumes were evaluated. Also, the activity of Caspase 3 was assessed in different groups. The group which received combination cell therapy had better neurological examination and less brain lesion. Also the combination cell therapy group had the least Caspase 3 activity among the groups. The combination cell therapy is more effective than Mesenchymal stem cell therapy and neural stem cell therapy separately in treating the brain stroke in rats.

Triple combination therapy and zeaxanthin for the treatment of neovascular age-related macular degeneration: an interventional comparative study and cost-effectiveness analysis.

PubMed

Olk, R Joseph; Peralta, Enrique; Gierhart, Dennis L; Brown, Gary C; Brown, Melissa M

2015-01-01

Reports of triple combination therapy for neovascular age-related macular degeneration (AMD) suggest a benefit, as do reports for zeaxanthin. An interventional comparative study was thus undertaken to evaluate the efficacy of triple combination therapy with and without zeaxanthin, as well as the economic viability of the therapies. The cases of 543 consecutive eyes of 424 patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were reviewed. All eyes were treated with triple combination therapy (triple therapy) consisting of: (1) reduced-fluence photodynamic therapy with verteporfin, (2) intravitreal bevacizumab and (3) intravitreal dexamethasone. Therapy was repeated as necessary. One cohort of patients was also given supplementation with 20 mg of oral zeaxanthin (Zx) daily. The triple therapy group without Zx received a mean of 2.8 treatment cycles and 87 % of patients had stable or improved vision at 24 months. In the triple therapy group with Zx, the mean number of treatment cycles was 2.1, with 83 % of patients having stable or improved vision at 24 months. At 24 months, CNV developed in 12.5 % of fellow eyes treated with triple therapy alone; CNV developed in 6.25 % of eyes treated with triple therapy with Zx (p = 0.03). An average cost-utility analysis revealed that triple therapy was cost-effective with a cost-utility ratio of $26,574/QALY, while triple therapy with Zx was more cost-effective with an average cost-utility ratio of $19,962/QALY. The incremental cost-utility analysis assessing the addition of Zx to triple therapy disclosed Zx supplementation was very cost-effective at $5302/QALY. When it was assumed that triple therapy with Zx reduced fellow eye CNV development by 30.3 %, the incremental cost-utility dropped to (-$6332/QALY), indicating that adding Zx to triple therapy yielded greater patient value, and was also less expensive than using triple therapy alone. Triple therapy is comparatively effective and cost-effective. Considerably less treatment is needed than reported in monotherapy studies. The addition of oral Zx appears to further reduce the treatment cycles required, and possibly reduce the risk of CNV development in the fellow eye.

[Infrared radiation and magnetic field therapy ameliorates cartilage damage in rabbits with knee osteoarthritis].

PubMed

Sun, Jia-li; Fan, Jian-zhong; Song, Gui-zhi; Tan, Xiao-ming; Peng, Nan

2007-12-01

To evaluate the effect of infrared radiation and magnetic field therapy on cartilage damage in rabbits with knee osteoarthritis. Knee osteoarthritis was induced in 24 adult New Zealand rabbits by prolonged fixation of the knee joint in extension for 6 weeks. The rabbits were subsequently randomized into control group (without treatment), infrared therapy group, magnetic field therapy group and the combined infrared and magnetic field therapy group. At the end of the first, second and third weeks of the therapy, respectively, 2 rabbits from each group were sacrificed to observe the general changes and histopathology of the condylar cartilage of the femur, and the findings were assessed using Mankin scores. Compared with other groups, the rabbits in the combined therapy group showed significantly milder cartilage damage (including injury of the cartilage surface and chondrocyte's proliferation and disarrangement) with significantly lower Mankin scores (P<0.05). No significant differences were found in the findings between the two groups with exclusive infrared or magnetic field therapy (P>0.1). Combined infrared and magnetic field therapy can effectively alleviate cartilage destruction, shortens the disease course and enhance the therapeutic effects in rabbits with knee osteoarthritis.

The relationship between combination inhaled corticosteroid and long-acting beta-agonist use and severe asthma exacerbations in a diverse population

PubMed Central

Wells, Karen E.; Peterson, Edward L.; Ahmedani, Brian K.; Severson, Richard K.; Gleason-Comstock, Julie; Williams, L. Keoki

2012-01-01

Background Safety concerns surround the use of long-acting beta agonists (LABA) for the treatment of asthma, even in combination with inhaled corticosteroids (ICS) and particularly in high-risk subgroups. Objective To estimate the effect ICS therapy and fixed-dose ICS/LABA combination therapy on severe asthma exacerbations in a racially diverse population. Methods Inhaled corticosteroid and ICS/LABA exposure was estimated from pharmacy data for patients with asthma age 12 to 56 years who were members of a large health maintenance organization. Inhaled corticosteroid and ICS/LABA use was estimated for each day of follow-up to create a moving window of exposure. Proportional hazard models were used to assess the relationship between ICS and ICS/LABA combination therapy and severe asthma exacerbations (i.e., use of oral corticosteroids, asthma-related emergency department visit, or asthma-related hospitalization). Results Among the 1,828 patients who met the inclusion criteria, 37% were African American, 46% were treated with ICS therapy alone, and 54% were treated with an ICS/LABA combination. Models assessing the risk of severe asthma exacerbations among individuals using ICS treatment alone and ICS/LABA combination therapy suggested that the overall protective effect was as good or better for ICS/LABA combination therapy when compared with ICS treatment alone (hazard ratio [HR]=0.65 vs. HR=0.72, respectively). Analyses in several subgroups, including African American patients, showed a similar statistically significant protective association for combination therapy. Conclusion Treatment with ICS/LABA fixed combination therapy appeared to perform as well or better than ICS alone in reducing severe asthma exacerbations; this included multiple high-risk subgroups. PMID:22281166

Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia.

PubMed

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

2015-12-14

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

Quality of Artemisinin-based Combination Therapy for malaria found in Ghanaian markets and public health implications of their use.

PubMed

Tivura, Mathilda; Asante, Isaac; van Wyk, Albert; Gyaase, Stephaney; Malik, Naiela; Mahama, Emmanuel; Hostetler, Dana M; Fernandez, Facundo M; Asante, Kwaku Poku; Kaur, Harparkash; Owusu-Agyei, Seth

2016-10-28

Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regulatory bodies and law enforcement agencies. The presence and prevalence of substandard and counterfeit Artemisinin-based Combination Therapies need to be determined on open markets in Ghana; a review of the current policy; identifying any gaps and making recommendations on actions to be taken in addressing gaps identified are essential as the data provided and recommendations made will help in ensuring effective control of malaria in Ghana. A field survey of antimalarial drugs was conducted in the central part of Ghana. The amount of active pharmaceutical ingredient in each Artemisinin-based Combination Therapy sample identified in the survey was measured using high performance liquid chromatographic analyses. Active pharmaceutical ingredient within the range of 85-115 % was considered as standard and active pharmaceutical ingredient results out of the range were considered as substandard. All samples were screened to confirm stated active pharmaceutical ingredient presence using mass spectrometry. A total of 256 Artemisinin-based Combination Therapies were purchased from known medicine outlets, including market stalls, hospitals/clinics, pharmacies, drug stores. Artemether lumefantrine (52.5 %) and artesunate amodiaquine (43.2 %) were the predominant Artemisinin-based Combination Therapies purchased. Of the 256 Artemisinin-based Combination Therapies purchased, 254 were tested, excluding two samples of Artesunate-SP. About 35 % of Artemisinin-based Combination Therapies were found to be substandard. Nine percent of Artemisinin-based Combination Therapies purchased were past their expiry date; no counterfeit (falsified) medicine samples were detected by either high performance liquid chromatographic or mass spectrometry. A high proportion of Artemisinin-based Combination Therapies sold in central Ghana were found to be substandard. Manufacturing of medicines that do not adhere to good manufacturing practices may have contributed to the poor quality of the Artemisinin-based Combination Therapies procured. A strict law enforcement and quality monitoring systems is recommended to ensure effective malaria case management as part of malaria control.

State-of-the-art: Immunosuppression and biologic therapy.

PubMed

Sandborn, William J

2010-01-01

Azathioprine and 6-mercaptopurine are orally administered immunosuppressive drugs which are effective for the treatment of Crohn's disease and ulcerative colitis. Azathioprine is rapidly converted to 6-mercaptopurine after administration. 6-Mercaptopurine is then either converted to the putative active metabolites, the 6-thioguinine nucleotides, or inactivated by the enzyme xanthine oxidase to 6-thiouric acid or alternatively inactivated to 6-methylmercaptopurine by the enzyme thiopurine methyltransferase. Thiopurine methyltransferase activity is genetically determined, with one in 300 patients having low or absent enzyme activity, one in 10 patients having intermediate enzyme activity, and 9 in 10 patients having normal enzyme activity. Patients with intermediate or low thiopurine methyltransferase activity are at risk for early leukopenia. Higher erythrocyte 6-thioguinine nucleotide concentrations are associated with a greater likelihood of clinical response. Azathioprine is modestly effective for Crohn's disease and ulcerative colitis. Toxicity associated with azathioprine includes infection and lymphoma. Anti-TNF therapy with infliximab, adalimumab, and certolizumab pegol is effective for induction and maintenance treatment of Crohn's disease, and infliximab is effective for ulcerative colitis. Toxicity associated with anti-TNF therapy includes infection and lymphoma. Combination therapy with infliximab and azathioprine is more effective for inducing and maintaining steroid-free remission and mucosal healing then monotherapy with either drug alone. Strategies to reduce immunogenicity of anti-TNF agents include combination therapy with azathioprine and administration of a loading dose followed by systematic maintenance dosing. Higher serum trough concentrations of infliximab occur more frequently in patients receiving combination therapy with azathioprine and are associated with better clinical outcomes. Combination therapy is associated with an increased relative risk of opportunistic infection, but is not associated with an increased absolute risk of serious infection. Clinical practice should change such that combination therapy with an anti-TNF agent and azathioprine replace azathioprine in patients failing first line therapy with mesalamine and/or steroids. Copyright © 2010 S. Karger AG, Basel.

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

NASA Astrophysics Data System (ADS)

Yuan, Chenyan; An, Yanli; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng

2014-08-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression.

Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts.

PubMed

Zhao, Kai; Yang, Shang-You; Geng, Jun; Gong, Xuan; Gong, Weiming; Shen, Lin; Ning, Bin

2018-06-01

Investigate whether rAAV-anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV-eGFP, radiotherapy, rAAV-anginex, combination therapy) were applied to determine effects on proliferation of endothelial cells (ECs) and G-292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor-bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of metastatic nodules and wet weight of metastases. The proliferation of ECs and the tumor volumes in combination therapy group were inhibited more effectively than the other three groups at end point (P < 0.05). Cell clone assay showed anginex had radiosensitization effect on ECs. Immunohistochemistry showed tumors from mice treated with combination therapy exhibited the lowest MVD and proliferation rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA and TUNEL assays (P < 0.05). Combination therapy also induced the fewest metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV-anginex combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We conclude that the primary mechanism of this process may be due to sensitizing effect of anginex to radiotherapy. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

PubMed

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

2017-01-01

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

[Effect of interferon and ribavirin combination therapy in sixty-two patients with chronic hepatitis C originating from a single blood donor].

PubMed

Liu, San-du; Cheng, Ming-liang; Ren, Hong; Yang, Qing-kun; Shu, De-yun

2012-08-01

To investigate the efficacy of interferon alpha 2 b plus ribavirin combination therapy in sixty-two patients with chronic hepatitis c (CHC) infection originating from a single blood donor. The 62 patients who developed CHC following blood transfusion from a known single infected donor were treated with interferon and ribavirin combination therapy for 48 weeks and followed-up for 96 weeks. The therapy regimen consisted of subcutaneous administration of 3-500 MIU interferon alpha 2 b every other day and daily oral administration of 0.6-1.0 g of ribavirin. Patients were monitored during treatment and in follow-up for sustained virological response (SVR), early virology response (EVR), treatment end virology response (ETVR), biochemical response of withdrawals, and side effects. The SVR rate was 83.9% (52/62). The EVR rate was 95.2% (59/62). The ETVR rate was 87.1% (54/62). The biochemical response rate after withdrawal of treatment was 100.0%. Eight patients developed mildly abnormal thyroid function as a result of the interferon therapy, but all were able to complete the antiviral treatment regimen under the care of endocrinologists. Younger age, relatively short course of disease, low viral load, and better compliance, but not sex, were correlated to curative effect of the combination therapy. Interferon alpha 2 b plus ribavirin combination therapy had a significant curative effect on a group of 62 CHC patients originating from a single case, with 52 of the patients showing SVR out to 96 weeks after therapy. Antiviral treatment is recommended for hepatitis C virus-positive patients to eradicate the virus and prevent disease progression.

Promises and Dangers of Combination Therapy.

PubMed

Kruis, Wolfgang; Nguyen, Phuong G; Morgenstern, Julia

2017-01-01

The efficiency of the existing methods of treating inflammatory bowel disease (IBD) is limited. There are 2 ways to address this problem - either create new treatment modalities or optimize current therapies. Optimisation may be accomplished by using combinations of established therapeutic strategies. With regard to topically acting compounds such as 5-aminosalicylic acid, combining oral and rectal preparations is a commonly used method. Another commonly used combination is anti-tumor necrosis factor (TNF)-α antibody modalities together with immunosuppressants (thiopurines, methotrexate). Several aspects favour those combinations such as increased effectivity, prevention of immunogenicity and perhaps less adverse events. Currently, discussion on directly additive therapeutic effects is in progress, which have been demonstrated in some clinical trials. As on date, the combination of infliximab with azathioprine is most likely the most effective treatment of Crohn's disease. On the other hand, a combination therapy with both compounds affecting the immune system has, of course, risks. For sure, the frequency with which serious infectious complications are arising is increasing. Furthermore, the number of patients experiencing malignancies such as hepato-splenic lymphoma or melanoma is strongly suspected to be on the rise. In summary, combinations of current treatments for IBD are widely established. Various strategies have been studied and significant improvements of therapeutic effects have been demonstrated. Unfortunately, some of those proven combinations increase therapeutic risks, for example, increase the frequency of serious infections and also of some malignancies. Therefore, great caution has to be exercised when applying combination therapies. © 2017 S. Karger AG, Basel.

Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

NASA Astrophysics Data System (ADS)

Liu, Xiaoguang; Li, Jie; Liu, Timon Chengyi; Yuan, Jianqin; Luo, Qingming

2008-12-01

The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

Two drugs are better than one. A short history of combined therapy of ovarian cancer

PubMed Central

Gajek, Arkadiusz; Marczak, Agnieszka

2014-01-01

Combined therapy of ovarian cancer has a long history. It has been applied for many years. The first drug which was commonly combined with other chemotherapeutics was cisplatin. It turned out to be effective given together with alkylating agents as well as with taxanes. Another drug which is often the basis of first-line therapy is doxorubicin. The use of traditional chemotherapy is often limited due to side effects. This is why new drugs, targeted specifically at cancer cells (e.g. monoclonal antibodies or epidermal growth factor receptor inhibitors), offer a welcome addition when used in combination with conventional anticancer agents. Drugs applied in combination should be synergistic or at least additive. To evaluate the type of interaction between drugs in a plausible sequence, isobolographic analysis is used. This method allows one to assess whether the two agents could make an efficient combination, which might improve the therapy of ovarian cancer. PMID:26793017

Therapeutic effects of combination using glucosamine plus tacrolimus (FK-506) on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, C-H; Cheong, K A; Park, C D; Lee, A-Y

2012-05-01

Tacrolimus (FK-506) has been found to exhibit potent inhibitory effects on spontaneously developed dermatitis. We previously showed that glucosamine prevents the development of Atopic dermatitis (AD)-like skin lesions in NC/Nga mice. The aims of our study were to investigate the synergistic therapeutic efficacy of combination of glucosamine plus FK-506 in dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice and to determine the underlying therapeutic mechanisms. The Df-induced NC/Nga mice with a clinical score of 8 were used for treatment with glucosamine (500 mg/kg) alone, FK-506 (1.0 mg/kg) or in combination. The synergistic effects of combination therapy were evaluated by dermatitis scores, skin histology and immunological parameters such as IgE, Th2-mediated cytokines and chemokines, CD3(+) T cells and CLA(+) T cells. Combined therapy using glucosamine plus FK-506 improved the development of AD-like skin lesions as exemplified by a significant decrease in total skin symptom severity scores. The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3(+) T cells and CLA(+) cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

PubMed Central

Quirk, Shannon K.; Shure, Anna K.; Agrawal, Devendra K.

2015-01-01

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies as well as specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

Marital Therapy as a Treatment for Depression.

ERIC Educational Resources Information Center

Jacobson, Neil S.; And Others

1991-01-01

Compared cognitive-behavioral therapy (CT), behavioral marital therapy (BMT), and combination of two therapies in alleviation of wives' depression and enhancement of marital satisfaction. Found BMT less effective than CT for depression in maritally nondistressed couples. For maritally distressed couples, two treatments were equally effective.…

The combined effects of cold therapy and music therapy on pain following chest tube removal among patients with cardiac bypass surgery.

PubMed

Yarahmadi, Sajad; Mohammadi, Nooredin; Ardalan, Arash; Najafizadeh, Hassan; Gholami, Mohammad

2018-05-01

Chest tube removal is an extremely painful procedure and patients may not respond well to palliative therapies. This study aimed to examine the effect of cold and music therapy individually, as well as a combination of these interventions on reducing pain following chest tube removal. A factorial randomized-controlled clinical trial was performed on 180 patients who underwent cardiac surgery. Patients were randomized into four groups of 45. Group A used ice packs for 20 minutes prior to chest tube removal. Group B was assigned to listen to music for a total length of 30 minutes which started 15 minutes prior to chest tube removal. Group C received a combination of both interventions; and Group D received no interventions. Pain intensity was measured in each group every 15 minutes for a total of 3 readings. Analysis of variance, Tukey and Bonferroni post hoc tests, as well as repeated measures ANOVA were employed for data analysis. Cold therapy and combined method intervention effectively reduced the pain caused by chest tube removal (P < 0.001). Additionally, there were no statistically significant difference in pain intensity scores between groups at 15 minutes following chest tube removal (P = 0.07). Cold and music therapy can be used by nursing staff in clinical practice as a combined approach to provide effective pain control following chest tube removal. Copyright © 2018 Elsevier Ltd. All rights reserved.

Combination therapy in combating cancer

PubMed Central

Mokhtari, Reza Bayat; Homayouni, Tina S.; Baluch, Narges; Morgatskaya, Evgeniya; Kumar, Sushil; Das, Bikul; Yeger, Herman

2017-01-01

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the “medically underserved”. In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012. PMID:28410237

Is there a role for rifampicin, ofloxacin and minocycline (ROM) therapy in the treatment of leprosy? Systematic review and meta-analysis.

PubMed

Setia, Maninder S; Shinde, Santosh S; Jerajani, Hemangi R; Boivin, Jean-François

2011-12-01

A combination of rifampicin, ofloxacin and minocycline (ROM) is one of the newer recommendations for treatment of leprosy. We performed a systematic review and a meta-analysis of studies that had evaluated the efficacy of ROM therapy in treatment of paucibacillary and multibacillary leprosy patients. Studies were identified by searching the PubMed, Embase, LILACS and Cochrane databases. Data were abstracted from all relevant studies, and fixed effects models were used to calculate the summary estimate of effect in paucibacillary and multibacillary leprosy patients. Six studies comparing ROM therapy to multidrug therapy and eight studies that evaluated the effect of ROM therapy alone (no comparison group) were included in the review and meta-analysis. The combined estimate for single dose ROM vs. multidrug therapy in paucibacillary leprosy patients suggested that ROM was less effective than multidrug therapy in these patients [relative risk: 0.91, 95% confidence intervals (CI): 0.86-0.97]. However, the combined estimate for multiple doses of ROM vs. multidrug therapy in multibacillary leprosy patients suggested that ROM was as effective as multidrug therapy in reducing bacillary indices in these patients (proportion change: -4%, 95% CI -31% to 23%). No major side effects were reported in either the ROM or the multidrug treatment groups. Single-dose ROM therapy was less effective than multidrug therapy in paucibacillary patients. However, there are insufficient data to come to a valid conclusion on the efficacy of multidose ROM therapy in multibacillary leprosy, and additional studies with ROM therapy in multibacillary leprosy are needed. Furthermore, multiple doses may be considered as another alternative even for paucibacillary patients, and randomised controlled trials of this therapy may be useful to understand its contribution in the treatment and control of leprosy. © 2011 Blackwell Publishing Ltd.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Integrative Therapies for Low Back Pain That Include Complementary and Alternative Medicine Care: A Systematic Review

PubMed Central

Rose, Kevin; Kadar, Gena E.

2014-01-01

Study Design: Systematic review of the literature. Objective: To evaluate whether an integrated approach that includes different Complementary and Alternative Medicine (CAM) therapies combined or CAM therapies combined with conventional medical care is more effective for the management of low back pain (LBP) than single modalities alone. Summary of Background Data: LBP is one of the leading causes of disability worldwide, yet its optimal management is still unresolved. Methods: The PRISMA Statement guidelines were followed. The Cochrane Back Review Group scale was used to rate the quality of the studies found. Results: Twenty-one studies were found that met the inclusion criteria. The CAM modalities used in the studies included spinal manipulative therapy, acupuncture, exercise therapy, physiotherapy, massage therapy, and a topical ointment. Twenty studies included acupuncture and/or spinal manipulative therapy. Nine high quality studies showed that integrative care was clinically effective for the management of LBP. Spinal manipulative therapy combined with exercise therapy and acupuncture combined with conventional medical care or with exercise therapy appears to be promising approaches to the management of chronic cases of LBP. Conclusions: There is support in the literature for integrated CAM and conventional medical therapy for the management of chronic LBP. Further research into the integrated management of LBP is clearly needed to provide better guidance for patients and clinicians. PMID:25568825

Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

PubMed

Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

2017-06-01

Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

A cost-effectiveness analysis of combination antiplatelet therapy for high-risk acute coronary syndromes: clopidogrel plus aspirin versus aspirin alone.

PubMed

Schleinitz, Mark D; Heidenreich, Paul A

2005-02-15

Although clopidogrel plus aspirin is more effective than aspirin alone in preventing subsequent vascular events in patients with unstable angina, the cost-effectiveness of this combination has yet to be examined in this high-risk population. To determine the cost-effectiveness of clopidogrel plus aspirin compared with aspirin alone. Cost-utility analysis. Published literature. Patients with unstable angina and electrocardiographic changes or non-Q-wave myocardial infarction. time horizon: Lifetime. Societal. Combination therapy with clopidogrel, 75 mg/d, plus aspirin, 325 mg/d, for 1 year, followed by aspirin monotherapy, was compared with lifelong aspirin therapy, 325 mg/d. Lifetime costs, life expectancy in quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio. Patients treated with aspirin alone lived 9.51 QALYs after their initial event and incurred expenses of 127,700 dollars; the addition of clopidogrel increased life expectancy to 9.61 QALYs and costs to 129,300 dollars. The incremental cost-effectiveness ratio for clopidogrel plus aspirin compared with aspirin alone was 15,400 dollars per QALY. The analysis of 1 year of therapy was robust to all sensitivity analyses. In the probabilistic sensitivity analysis, fewer than 3% of simulations resulted in cost-effectiveness ratios over 50,000 dollars per QALY. The cost-effectiveness of longer combination therapy depends critically on the balance of thrombotic event rates, durable efficacy, and the increased bleeding rate in patients taking clopidogrel. This analysis may not apply to patients with severe heart failure, those undergoing long-term anticoagulant therapy, those recently managed with revascularization, or those undergoing short-term treatment with glycoprotein IIb/IIIa inhibitors. In patients with high-risk acute coronary syndromes, 1 year of therapy with clopidogrel plus aspirin results in greater life expectancy than aspirin alone, at a cost within the traditional limits of cost-effectiveness. The durable efficacy of clopidogrel relative to the risk for hemorrhage should be further explored before more protracted therapy can be recommended.

Economic Evaluation of the Combined Use of Warfarin and Low-dose Aspirin Versus Warfarin Alone in Mechanical Valve Prostheses.

PubMed

El-Hamamsy, Manal H; Elsisi, Gihan H; Eldessouki, Randa; Elmazar, Mohamed M; Taha, Ahmed S; Awad, Basma F; Elmansy, Hossam

2016-08-01

The use of combined therapy of antiplatelet and anticoagulant versus anticoagulant alone to reduce instances of thromboembolic events in patients with heart valve prostheses is an established standard of care in many countries but not in Egypt. A previous Markov model cost-effectiveness study on Egyptian patients aged 50-60 years demonstrated that the combined therapy reduces the overall treatment cost. However, due to the lack of actual real-world data on cost-effectiveness and the limitation of the Markov model study to 50- to 60-year-old patients, the Egyptian medical community is still questioning whether the added benefit is worth the cost. To assess, from the perspective of the Egyptian health sector, the cost-effectiveness of the combined use of warfarin and low-dose aspirin (75 mg) versus that of warfarin alone in patients with mechanical heart valve prostheses who began therapy between the age of 15 and 50 years. An economic evaluation was conducted alongside a randomized, controlled trial to assess the cost-effectiveness of the combined therapy in patients with mechanical valve prostheses. A total of 316 patients aged between 15 and 50 years were included in the study and randomly assigned to a group treated with both warfarin and aspirin or a group treated with warfarin alone. The patients in the combined therapy group exhibited a significantly longer duration of protection against the first event. Fewer primary events were observed in the patients treated with warfarin plus aspirin than in those treated with warfarin alone (1.4 %/year, vs. 4.8 %/year), and a higher mean quality-adjusted life-years (QALYs) value over 4 years was obtained for the group treated with warfarin plus aspirin (difference 0.058; 95 % CI 0.013-0.118), although this difference did not reach a conventional level of statistical significance. The total costs over a 4-year period were lower with the combined therapy (difference -US$244; 95 % CI -US$483.1 to -US$3.8), which yielded an incremental cost-effectiveness ratio of -US$4206 per QALY gained. Thus, the combined therapy was dominant. All costs were reported in US dollars (USD) for the financial year 2014. The results of this analysis indicate that from the perspective of the Egyptian health sector, the addition of aspirin to the typical warfarin therapy is more effective and less costly for patients with mechanical valve prostheses than treatment with warfarin alone. This combined strategy could be adopted to prevent the complications of mechanical valve prostheses. Our study adds to the body of evidence supporting the option of warfarin-plus-aspirin therapy for patients with mechanical valve prostheses.

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

PubMed

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

2017-05-01

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

Comparison of the effects of auditory subliminal stimulation and rational-emotive therapy, separately and combined, on self-concept.

PubMed

Möller, A T; Kotzé, H F; Sieberhagen, K J

1993-02-01

The present study investigated the effects on self-concept of Rational-Emotive Therapy and auditory subliminal stimulation (separately and in combination) on 141 undergraduate students with self-concept problems. They were randomly assigned to one of four groups receiving either Rational-Emotive Therapy, subliminal stimulation, both, or a placebo treatment. Rational-Emotive Therapy significantly improved scores on all the dependent measures (cognition, self-concept, self-esteem, anxiety), except for behavior. Results for the subliminal stimulation group were similar to those of the placebo treatment except for a significant self-concept improvement and a decline in self-concept related irrational cognitions. The combined treatment yielded results similar to those of Rational-Emotive Therapy, with tentative indications of continued improvement in irrational cognitions and self-concept from posttest to follow-up.

Treatment With mANT2 shRNA Enhances Antitumor Therapeutic Effects Induced by MUC1 DNA Vaccination

PubMed Central

Choi, Yun; Jeon, Yong H; Jang, Ji-Young; Chung, June-Key; Kim, Chul-Woo

2011-01-01

In this study, we developed a combination therapy (pcDNA3/hMUC1+mANT2 shRNA) to enhance the efficiency of MUC1 DNA vaccination by combining it with mANT2 short hairpin RNA (shRNA) treatment in immunocompetent mice. mANT2 shRNA treatment alone increased the apoptosis of BMF cells (B16F1 murine melanoma cell line coexpressing an MUC1 and Fluc gene) and rendered BMF tumor cells more susceptible to lysis by MUC1-associated CD8+ T cells. Furthermore, combined therapy enhanced MUC1 associated T-cell immune response and antitumor effects, and resulted in a higher cure rate than either treatment alone (pcDNA3/hMUC1 or mANT2 shRNA therapy alone). Human MUC1 (hMUC1)-loaded CD11c+ cells in the draining lymph nodes of BMF-bearing mice treated with the combined treatment were found to be most effective at generating hMUC1-associated CD8+IFNγ+ T cells. Furthermore, the in vitro killing activities of hMUC1-associated cytotoxic T cells (CTLs) in the combined therapy were greater than in the respective monotherapies. Cured animals treated with the combined treatment rejected a rechallenge by BMF cells, but not a rechallenge by B16F1-Fluc cells at 14 days after treatment, and showed MUC1 antigen-associated immune responses. These results suggest that combined therapy enhances antitumor activity, and that it offers an effective antitumor strategy for treating melanoma. PMID:21063392

Combined intranasal nerve growth factor and ventricle neural stem cell grafts prolong survival and improve disease outcome in amyotrophic lateral sclerosis transgenic mice.

PubMed

Zhong, Shi-Jiang; Gong, Yan-Hua; Lin, Yan-Chen

2017-08-24

Amyotrophic lateral sclerosis (ALS) is a fatal disease that selectively involves motor neurons. Neurotrophic factor supplementation and neural stem cell (NSC) alternative therapy have been used to treat ALS. The two approaches can affect each other in their pathways of action, and there is a possibility for synergism. However, to date, there have been no studies demonstrating the effects of combined therapy in the treatment of ALS. In this study, for the first time, we adopted a method involving the intranasal administration of nerve growth factor combined with lateral ventricle NSC transplantation using G93A-SOD1 transgenic mice as experimental subjects to explore the treatment effect of this combined therapy in ALS. We discover that the combined therapy increase the quantity of TrkA receptors, broaden the migration of exogenous NSCs, further promote active proliferation in neurogenic regions of the brain and enhance the preservation of motor neurons in the spinal cord. Regarding physical activity, the combined therapy improved motor functions, further postponed ALS onset and extended the survival time of the mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Mirror therapy combined with functional electrical stimulation for rehabilitation of stroke survivors' ankle dorsiflexion.

PubMed

Salhab, Ghadir; Sarraj, Ahmad Rifaii; Saleh, Soha

2016-08-01

This study investigates the effect of combining both mirror therapy with Electrical Stimulation (ES) on improvement of the function of lower extremity compared to conventional therapy. 18 stroke survivors (sub acute stage) were recruited, 9 of them were randomly assigned to receive conventional treatment and another 9 started the mirror therapy combined with ES treatment. Duration of each session in both interventions was 50 minutes, done 4 times per week over two weeks. After 2 weeks, subjects took one week rest before switching they type of treatment; those started with conventional therapy continued with mirror therapy combined with ES, and vice versa. The duration of this phase was 2 weeks with same schedule as the 1st one. Ankle dorsi-flexion range of motion, lower extremity sensory-motor function, and walking duration were measured at baseline, after 1st 2 weeks, and immediately after the last two weeks, and 4 weeks after end of training (retention test). Repeated Measures ANCOVA was done to compare outcome measures scores in both groups and between all testing days, and paired T-test was used measure the difference between groups. Significant increase in all outcome measures was found after the (MT+ES) training, which is higher than conventional therapy training (p<;0.0001). In conclusion, the results suggest that combination of mirror therapy and ES is more effective than conventional therapy in improving lower limb motor function after stroke.

850nm light-emitting-diode phototherapy plus low-dose tacrolimus (FK-506) as combination therapy in the treatment of Dermatophagoides farinae-induced atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

Kim, Chang-Hyun; Cheong, Kyung Ah; Lee, Ai-Young

2013-11-01

Light emitting diode (LED) phototherapy is an effective alternative for the treatment of inflammatory skin disorders. Tacrolimus (FK-506) is a potent immunomodulating agent, which has been used to treat AD. Combination therapy is often used in the treatment of AD to improve therapeutic efficacy or to reduce the dose of each drug. To investigate the therapeutic efficacy of monotherapy with either 850nm LED phototherapy or low-dose FK-506, and combination therapy in Dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice. The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with LED (10 and 25J/cm(2)) alone, low-dose FK-506 (1mg/kg) or in combination. The synergistic effects of combined therapy were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, such as IgE, NO, Th2-mediated cytokines and chemokines. Combination therapy with 850nm (25J/cm(2)) LED and low-dose FK-506 showed a significant reduction in the severity of skin lesions. Combined therapy decreased in the serum level of IgE, NO, and in the splenic level of Th2-mediated cytokines and chemokines. Combination therapy significantly also reduced the inflammatory cellular infiltrate into the skin lesions. Moreover, combination therapy led to recovery of skin barrier function in the skin lesions. The use of combination of LED phototherapy and low-dose immunosuppressant improved Df-induced AD-like skin lesions in an NC/Nga mouse model by dominantly reducing IgE, NO, suppressing Th2-mediated immune responses, and inhibiting inflammatory cells, as well as improving skin barrier function. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Use of combined intracorporal injection and a phosphodiesterase-5 inhibitor therapy for men with a suboptimal response to sildenafil and/or vardenafil monotherapy after radical retropubic prostatectomy.

PubMed

Mydlo, Jack H; Viterbo, Rosalia; Crispen, Paul

2005-04-01

To report experience with combined therapy using intracorporal injection (ICI) of alprostadil and oral phosphodiesterase 5 (PDE-5) inhibitors for the minimally invasive treatment of erectile dysfunction (ED) after radical prostatectomy (RP), as PDE-5 inhibitors are effective but a few patients may have a suboptimal response. In a retrospective study, 34 men (aged 46-66 years) had a nerve-sparing retropubic RP and subsequent ED. Patients were titrated on sildenafil citrate or vardenafil to maximum doses. All had a suboptimal response after a maximum of eight doses of oral therapy and were then treated with ICI therapy using 15 or 20 microg alprostadil. Erectile function was assessed with the Sexual Health Inventory for Men (SHIM). Of the 32 patients who continued combined therapy, 22 (68%) had an improvement in erectile function after ICI therapy, as assessed by the SHIM score. On follow-up, 36% of these patients used ICI therapy only intermittently, instead of regularly, as they felt that this was adequate enough for good results. PDE-5 oral pharmacotherapy is the most commonly used effective therapy for ED but may not be as effective in patients who have radical surgery; the addition of testosterone patches may have side-effects or be considered a risk in patients with a history of prostate cancer. The use of ICI therapy as an adjunct or maintenance therapy to their oral medication may be another alternative in these patients.

Effectiveness of Behavioral Therapy for Chronic Low Back Pain: A Component Analysis.

ERIC Educational Resources Information Center

Turner, Judith A.; And Others

1990-01-01

Evaluated effects of group behavioral therapy including aerobic exercise, behavioral therapy alone, and aerobic exercise alone on pain and physical and psychological disability among mildly disabled chronic low-back-pain patients (n=96). The combined behavioral therapy and exercise group improved significantly more pretreatment to posttreatment…

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

PubMed

Saito, Ikuo; Fujikawa, Keita; Saruta, Takao

2008-07-01

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

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors.

PubMed

Grenier, Jeremy M; Yeung, Stephen T; Qiu, Zhijuan; Jellison, Evan R; Khanna, Kamal M

2017-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1 b , on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1 b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection.

Combining Adoptive Cell Therapy with Cytomegalovirus-Based Vaccine Is Protective against Solid Skin Tumors

PubMed Central

Grenier, Jeremy M.; Yeung, Stephen T.; Qiu, Zhijuan; Jellison, Evan R.; Khanna, Kamal M.

2018-01-01

Despite many years of research, cancer vaccines have largely been ineffective in the treatment of established cancers. Many barriers to immune-mediated destruction of malignant cells exist, and these likely limit the efficacy of cancer vaccines. In this study, we sought to enhance the efficacy of a cytomegalovirus (CMV)-based vaccine targeting melanoma by combining vaccination with other forms of immunotherapy. Adoptive cell therapy in humans and in animal models has been shown to be effective for tumor regression. Thus, in this study, we assessed whether CMV-based vaccines in combination with adoptively transferred antitumor T cells could provide greater antitumor protection than either therapy alone. Our results show that adoptive cell therapy greatly enhanced the antitumor effects of CMV-based vaccines targeting the foreign model antigen, OVA, or the melanoma differentiation antigen, gp100. Combination adoptive cell therapy and vaccination induced the upregulation of the inhibitory ligands, PD-L1, and Qa-1b, on B16 tumor cells. This expression paralleled the infiltration of tumors by vaccine-stimulated T cells which also expressed high levels of the receptors PD-1 and NKG2A/C/E, suggesting a potential mechanism of tumor immune evasion. Surprisingly, therapeutic blockade of the PD-1/PD-L1 and NKG2A/Qa-1b axes did not delay tumor growth following vaccination, suggesting that the presence of inhibitory ligands within malignant tissue may not be an effective biomarker for successful combination therapy with CMV-based vaccines. Overall, our studies show that therapeutic CMV-based vaccines in combination with adoptive T cell transfer alone are effective for tumor rejection. PMID:29387061

The effect of combined therapies on recovery after acquired brain injury: Systematic review of preclinical studies combining enriched environment, exercise, or task-specific training with other therapies.

PubMed

Malá, Hana; Rasmussen, Camilla Pihl

2017-01-01

Acquired brain injuries (ABI) have devastating effects for the affected individual as well as society. Many studies have investigated the effect of different monotherapies. However, functional recovery is typically only partial. One possible strategy to promote a greater degree of recovery is to apply monotherapies in combination with one or more treatments. The objective of this systematic review is to investigate if approaches combining enriched environment (EE), exercise, or task-specific training with other monotherapies, further enhance the degree of recovery after ABI. Scopus, PsychINFO, and PubMed databases were searched in March 2016 with the following search strings: exercise (or) enriched environment (or) environmental enrichment (or) rehabilitation (and) traumatic brain injury (or) ischemia (or) stroke (and) rat (or) rodent. Studies were included if they (1) were in English, (2) used adult animals subjected to brain injury, (3) included EE, and/or exercise, and/or task-specific training as post-injury treatment strategies, (4) included at least one group receiving another monotherapy. Out of 2.168 hits, 29 studies fulfilled the inclusion criteria. Despite several trends for enhanced recovery after combined therapies, this systematic review of 29 studies does not indicate that combined therapies confer consistent combined effects on motor, cognitive, or cerebral recovery according to present criteria for combined effect. Combined treatments continue to provide hope for enhanced recovery after ABI, however, the research area is in its infancy. This systematic review does not provide conclusive evidence. This is likely due to sparse knowledge regarding optimal treatment parameters. Combined treatments, however, hold the best promise regarding treatment of the complex changes induced by ABI.

Use of Hematopoietic Growth Factor in the Management of Hematological Side Effects Associated to Antiviral Treatment for Hcv Hepatitis

PubMed Central

Mancino, Paola; Falasca, Katia; Ucciferri, Claudio; Pizzigallo, Eligio; Vecchiet, Jacopo

2010-01-01

Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR). To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection. PMID:21415945

Combination therapy for treatment or prevention of atherosclerosis: Focus on the lipid-RAAS interaction☆

PubMed Central

Koh, Kwang Kon; Han, Seung Hwan; Oh, Pyung Chun; Shin, Eak Kyun; Quon, Michael J.

2010-01-01

Large clinical trials demonstrate that control of blood pressure or hyperlipidemia reduces risk for cardiovascular events by ~30%. Factors that may further reduce remaining risk are not definitively established. One potential target is atherosclerosis, a crucial feature in the pathogenesis of cardiovascular diseases whose development is determined by multiple mechanism including complex interactions between endothelial dysfunction and insulin resistance. Reciprocal relationships between endothelial dysfunction and insulin resistance as well as cross-talk between hyperlipidemia and the rennin–angiotensin–aldosterone system may contribute to development of atherosclerosis. Therefore, one appealing strategy for prevention or treatment of atherosclerosis may be to simultaneously address several risk factors with combination therapies that target multiple pathogenic mechanisms. Combination therapy with statins, peroxisome proliferators-activated receptor agonists, and rennin–angiotensin–aldosterone system blockers demonstrate additive beneficial effects on endothelial dysfunction and insulin resistance when compared with monotherapies in patients with cardiovascular risk factors. Additive beneficial effects of combined therapy are mediated by both distinct and interrelated mechanisms, consistent with both pre-clinical and clinical investigations. Thus, combination therapy may be an important concept in developing more effective strategies to treat and prevent atherosclerosis, coronary heart disease, and co-morbid metabolic disorders characterized by endothelial dysfunction and insulin resistance. PMID:19800624

The velocity of antihypertensive effect of losartan/hydrochlorothiazide and angiotensin II receptor blocker.

PubMed

Metoki, Hirohito; Ohkubo, Takayoshi; Kikuya, Masahiro; Asayama, Kei; Inoue, Ryusuke; Obara, Taku; Hirose, Takuo; Sato, Michihiro; Hashimoto, Takanao; Imai, Yutaka

2012-07-01

The hypotensive effect and the time to attain the maximum antihypertensive effect (stabilization time) of losartan/hydrochlorothiazide (HCTZ) combination therapy and therapy with a maximal dose of angiotensin II receptor blockers (ARBs) in patients who failed to achieve adequate blood pressure (BP) control on a medium-dose of ARBs were compared by analyzing exponential decay functions using daily serial morning home BP measurements. Essential hypertensive patients treated with a medium dose of ARB, in whom a target home SBP (135 mmHg) was not achieved, were randomized into two groups: a combination group (n = 110) and a maximal-dose ARB group (n = 111). The combination therapy provided additional reduction of 5.2 mmHg [95% confidence interval (CI) 1.8 to 8.5 mmHg, P = 0.003] in home SBP over the maximal-dose ARB therapy in 8 weeks after randomization. A greater reduction in the home SBP values was seen in the combination group than in the maximal-dose ARB group from the second day after randomization on the basis of a linear mixed model. The maximum antihypertensive effect and stabilization time for home SBP were 10.9 ± 5.0 mmHg and 7.3 ± 29.7 days, respectively, in the combination group, whereas the corresponding values in the maximal-dose ARB group were 7.9 ± 2.6  mmHg and 122.3 ± 42.7 days, respectively, on the basis of a nonlinear mixed model. Changing from a medium dose of ARB monotherapy to combination therapy was more effective in the reduction of home SBP and achieved goal BP more rapidly than increasing the ARB dose. Home BP measurement is a useful tool for characterizing the antihypertensive effects of drugs.

Using photodynamic therapy to estimate effectiveness of innovative combined diclofenac and tazaroten therapy of disseminated actinic keratosis.

PubMed

Osiecka, Beata J; Jurczyszyn, Kamil; Nockowski, Piotr; Lipinski, Artur; Sieja, Agnieszka; Ziółkowski, Piotr

2015-01-01

Early diagnosis and therapy of precancerous lesions and malignant tumors belong to the most challenging tasks in modern medicine. Photodynamic diagnosis can help diagnose both precancerous lesions and early carcinoma. Actinic keratosis (AK) is the most common precancerous lesion of the skin. The available data show a high effectiveness of diclofenac in treating multifocal AK. We report a case of a 52-year-old woman who complained of multiple disseminated AK lesions predominantly on the lower limbs and trunk with a significant exacerbation within the last 6 months. Due to the spreading of disease and a high number of AK foci, as well as technical problems with visiting the hospital (PDT Laboratory), photodynamic therapy was not applied. The patient was treated for 2 months with a combination of local administration of 3% diclofenac and 0.1% tazaroten and 3% diclofenac only as a half side (left-right) comparison. The effects of therapy were later clinically evaluated and verified by means of photodynamic diagnosis (PDD) directly after therapy and at a follow-up examination 3 months later. The evaluation of treatment was blinded. Treatment with diclofenac only on the right side of the body resulted in clearing of 55% of all treated lesions, which increased to 60% three months after finishing therapy. On the left side of the body, where combined therapy (diclofenac 2 times daily on uneven dates and diclofenac once a day + tazaroten once a day on even dates) was used, 77.5% pathologic lesions disappeared, but this did not increase at follow up. The treatment of multifocal, disseminated AK is a difficult task and also burdensome for the patient due to side effects like scarring or burning and itching which occur during most therapies. Combined therapy with diclofenac and tazaroten supported by PDD may improve the effects of routine treatment of AK.

[Clinical observation on acupuncture by stages combined with exercise therapy for treatment of Bell palsy at acute stage].

PubMed

Qu, Yong

2005-08-01

To find out a method for increasing clinical therapeutic effect on Bell palsy at acute stage. Ninety cases of Bell palsy were randomly divided into an observation group, a control group I and a control group II, 30 cases in each group. They were treated respectively with acupuncture plus exercise therapy, simple acupuncture therapy, and simple exercise therapy, and their therapeutic effects were observed. The cured rate was 66.7% in the observation group, 53.3% in the control group I and 46.70% in the control group II, the observation group being better than the two control groups (P<0.05). Acupuncture by stage combined with exercise therapy can increase the therapeutic effect on Bell palsy at acute stage, and it is a better therapy for Bell palsy.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

A new treatment of hypertrophic and keloid scars with combined triamcinolone and verapamil: a retrospective study.

PubMed

Kant, S B; van den Kerckhove, E; Colla, C; Tuinder, S; van der Hulst, R R W J; Piatkowski de Grzymala, A A

2018-01-01

Since the management of keloid and hypertrophic scars still remains a difficult clinical problem, there is need for adequate, effective therapy. In this study, we explored for the first time the efficacy and the potential synergetic effect of combined triamcinolone and verapamil for the treatment of hypertrophic and keloid scars. The objective was to assess the efficacy of combined intralesional triamcinolone and verapamil therapy for hypertrophic and keloid scars. Fifty-eight patients with hypertrophic scars ( n  = 31) and keloid scars ( n  = 27) were included. A specific injection therapy scheme was applied. Five follow-up moments were chosen, with a maximum follow-up of nearly 2 years. The effects of combination therapy on scar pliability, thickness, relief, vascularization, surface area, pain, and pruritus were examined by means of the Patient and Observer Scar Assessment Scale (POSAS). Our results reveal a fast and abiding improvement of both keloid and hypertrophic scars after treatment with the combination therapy. All POSAS components showed a reduction in scar score, while scar relief, pain, itchiness, and surface area improved significantly ( P  < 0.05) in keloids. Significant improvement in hypertrophic scars was found in scar pigmentation, vascularization, pliability, thickness, pain, and surface area. Overall POSAS scores revealed statistically significant decreases between baseline and 3-4 months, 4-6 months, and >12 months after start of therapy in both keloids and hypertrophic scars. This study reveals that combined therapy of triamcinolone and verapamil results in overall significant scar improvement with a long-term stable result.Level of evidence: Level IV, therapeutic study.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

[Rational therapy of patients with essential hypertension and abdominal obesity with concomitant subclinical hypothyroidism].

PubMed

Pligovka, V M

2014-11-01

It was determined the characteristics of lipid status of patients with essential hypertension, abdominal obesity with concomitant subclinical hypothyroidism--mostly increased levels of total and LDL cholesterol. In assessing the effectiveness of statin therapy in combination with levothyroxine replacement therapy compared with statin monotherapy, combination therapy showed the best result in terms of achievement of target levels of both total cholesterol and LDL. The obtained results allow us to recommend the use of combination therapy for patients with hypertension, abdominal obesity with concomitant subclinical hypothyroidism in order to achieve the target values of LDL and thus to reduce the cardiovascular risk of these patients.

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

Comparison of the effects of 12 months of monthly minodronate monotherapy and monthly minodronate combination therapy with vitamin K2 or eldecalcitol in patients with primary osteoporosis.

PubMed

Ebina, Kosuke; Noguchi, Takaaki; Hirao, Makoto; Kaneshiro, Shoichi; Tsukamoto, Yasunori; Yoshikawa, Hideki

2016-05-01

The aim of this observational, nonrandomized study was to compare the effects of 12 months of monthly minodronate (MIN; 50 mg/month) monotherapy and MIN combination therapy with vitamin K2 (VK; 45 mg/day) or eldecalcitol (ELD; 0.75 μg/day) in treatment-naïve patients with primary osteoporosis. Patients (n = 193; 178 postmenopausal women and 15 men; mean age 71.6 years) were treated with (1) MIN monotherapy (n = 63), (2) MIN plus VK combination therapy (n = 50), or (3) MIN plus ELD combination therapy (n = 80) for 12 months. Changes in bone mineral density (BMD) and the levels of serum bone turnover markers were monitored. No significant difference was observed in baseline BMD among the three groups. After 12 months, BMD increased by 2.93, 4.65, and 6.55 % in the lumbar spine, 0.66, 2.57, and 3.42 % in the total hip, and 0.05, 2.06, and 3.58 % in the femoral neck in groups 1, 2, and 3, respectively. The BMD increase induced by MIN plus ELD combination therapy was significantly greater than that induced by MIN monotherapy in the lumbar spine (P = 0.0002), total hip (P = 0.003), and femoral neck (P = 0.004), and also that induced by MIN plus VK combination therapy in the lumbar spine (P = 0.03). MIN plus ELD combination therapy compared with MIN monotherapy resulted in a greater decrease in serum procollagen type I N-terminal propeptide levels (-37.4 % vs -54.6 %; P = 0.001) and tartrate-resistant acid phosphatase isoform 5b levels (-41.1 % vs -52.9 %; P = 0.009) at 3 months, and a greater decrease in procollagen type I N-terminal propeptide levels (-64.3 % vs -50.3 %; P = 0.03) and a decrease in intact parathyroid hormone levels (-12.3 % vs 14.0 %; P = 0.01) at 12 months. Combination therapy with MIN and VK or ELD for 12 months showed additive effects in decreasing the levels of bone turnover markers compared with MIN monotherapy, whereas MIN plus ELD combination therapy resulted in the highest BMD increase compared with MIN monotherapy and MIN plus VK combination therapy.

Single vs. combination immunotherapeutic strategies for glioma

PubMed Central

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

2017-01-01

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

Effect of constraint-induced movement therapy and mirror therapy for patients with subacute stroke.

PubMed

Yoon, Jin A; Koo, Bon Il; Shin, Myung Jun; Shin, Yong Beom; Ko, Hyun-Yoon; Shin, Yong-Il

2014-08-01

To evaluate the effectiveness of constraint-induced movement therapy (CIMT) and combined mirror therapy for inpatient rehabilitation of the patients with subacute stroke. Twenty-six patients with subacute stroke were enrolled and randomly divided into three groups: CIMT combined with mirror therapy group, CIMT only group, and control group. Two weeks of CIMT for 6 hours a day with or without mirror therapy for 30 minutes a day were performed under supervision. All groups received conventional occupational therapy for 40 minutes a day for the same period. The CIMT only group and control group also received additional self-exercise to substitute for mirror therapy. The box and block test, 9-hole Pegboard test, grip strength, Brunnstrom stage, Wolf motor function test, Fugl-Meyer assessment, and the Korean version of Modified Barthel Index were performed prior to and two weeks after the treatment. After two weeks of treatment, the CIMT groups with and without mirror therapy showed higher improvement (p<0.05) than the control group, in most of functional assessments for hemiplegic upper extremity. The CIMT combined with mirror therapy group showed higher improvement than CIMT only group in box and block test, 9-hole Pegboard test, and grip strength, which represent fine motor functions of the upper extremity. The short-term CIMT combined with mirror therapy group showed more improvement compared to CIMT only group and control group, in the fine motor functions of hemiplegic upper extremity for the patients with subacute stroke.

FAST INdiCATE Trial protocol. Clinical efficacy of functional strength training for upper limb motor recovery early after stroke: neural correlates and prognostic indicators.

PubMed

Pomeroy, Valerie M; Ward, Nick S; Johansen-Berg, Heidi; van Vliet, Paulette; Burridge, Jane; Hunter, Susan M; Lemon, Roger N; Rothwell, John; Weir, Christopher J; Wing, Alan; Walker, Andrew A; Kennedy, Niamh; Barton, Garry; Greenwood, Richard J; McConnachie, Alex

2014-02-01

Functional strength training in addition to conventional physical therapy could enhance upper limb recovery early after stroke more than movement performance therapy plus conventional physical therapy. To determine (a) the relative clinical efficacy of conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy for upper limb recovery; (b) the neural correlates of response to conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy; (c) whether any one or combination of baseline measures predict motor improvement in response to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Randomized, controlled, observer-blind trial. The sample will consist of 288 participants with upper limb paresis resulting from a stroke that occurred within the previous 60 days. All will be allocated to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Functional strength training and movement performance therapy will be undertaken for up to 1·5 h/day, five-days/week for six-weeks. Measurements will be undertaken before randomization, six-weeks thereafter, and six-months after stroke. Primary efficacy outcome will be the Action Research Arm Test. Explanatory measurements will include voxel-wise estimates of brain activity during hand movement, brain white matter integrity (fractional anisotropy), and brain-muscle connectivity (e.g. latency of motor evoked potentials). The primary clinical efficacy analysis will compare treatment groups using a multilevel normal linear model adjusting for stratification variables and for which therapist administered the treatment. Effect of conventional physical therapy combined with functional strength training versus conventional physical therapy combined with movement performance therapy will be summarized using the adjusted mean difference and 95% confidence interval. To identify the neural correlates of improvement in both groups, we will investigate associations between change from baseline in clinical outcomes and each explanatory measure. To identify baseline measurements that independently predict motor improvement, we will develop a multiple regression model. © 2013 The Authors. International Journal of Stroke published by John Wiley & Sons Ltd on behalf of World Stroke Organization.

Combination therapy of chitosan, gynostemma, and motherwort alleviates the progression of experimental rat chronic renal failure by inhibiting STAT1 activation

PubMed Central

Bai, Wenxia; Wang, Shudong; An, Shanshan; Guo, Mengjie; Gong, Guangming; Liu, Wenya; Ma, Shaoxin; Li, Xin; Fu, Jihua; Yao, Wenbing

2018-01-01

This study aimed to investigate the effect of single and combination therapy using chitosan (K), gynostemma (J), and motherwort (Y) on an experimental rat model of chronic renal failure (CRF) induced by adenine and the underlying mechanisms. CRF rats were treated with individual or combinational therapy with two or three of these agents. Biochemical indicators showed that the levels of blood urea nitrogen, creatinine and uric acid decreased and the levels of albumin and hemoglobin increased by single or combination therapy of these drugs. Drug treatment also decreased oxidative stress damage of renal tissues in CRF rats. Histopathological lesions were attenuated in each drug treatment group by various degrees. Additionally, drug treatment affected the expression of extracellular matrix (ECM) proteins including plasminogen activator inhibitor 1, collagen I, matrix metalloprotease-1, and tissue inhibitor of metalloproteinases 1. In particular, the combination therapy of K, J, and Y was superior to the respective monotherapy, which supported the prescription of KJY combination. We further studied the inhibitory effect of KJY on LPS-induced inflammation in RAW264.7 macrophages. The results showed that KJY inhibited LPS-induced secretion of inflammatory cytokines (Interferon-gamma, Interleukin-1 Beta, chemokine (C-X-C motif) ligand 10, cyclooxygenase-2 and Tumor necrosis factor-α in RAW264.7 macrophages. Combination therapy of KJY suppressed the protein expression of Cyclooxygenase-2 and inducible nitric oxide synthase in vivo and in vitro. Further study indicated that KJY inhibited STAT1 activation by down regulating p-STAT1 to exert anti-inflammatory effect and improve renal function in rats with chronic renal failure. PMID:29643988

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria.

PubMed

Stickles, Allison M; Smilkstein, Martin J; Morrisey, Joanne M; Li, Yuexin; Forquer, Isaac P; Kelly, Jane X; Pou, Sovitj; Winter, Rolf W; Nilsen, Aaron; Vaidya, Akhil B; Riscoe, Michael K

2016-08-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Atovaquone and ELQ-300 Combination Therapy as a Novel Dual-Site Cytochrome bc1 Inhibition Strategy for Malaria

PubMed Central

Smilkstein, Martin J.; Morrisey, Joanne M.; Li, Yuexin; Forquer, Isaac P.; Kelly, Jane X.; Pou, Sovitj; Winter, Rolf W.; Nilsen, Aaron; Vaidya, Akhil B.

2016-01-01

Antimalarial combination therapies play a crucial role in preventing the emergence of drug-resistant Plasmodium parasites. Although artemisinin-based combination therapies (ACTs) comprise the majority of these formulations, inhibitors of the mitochondrial cytochrome bc1 complex (cyt bc1) are among the few compounds that are effective for both acute antimalarial treatment and prophylaxis. There are two known sites for inhibition within cyt bc1: atovaquone (ATV) blocks the quinol oxidase (Qo) site of cyt bc1, while some members of the endochin-like quinolone (ELQ) family, including preclinical candidate ELQ-300, inhibit the quinone reductase (Qi) site and retain full potency against ATV-resistant Plasmodium falciparum strains with Qo site mutations. Here, we provide the first in vivo comparison of ATV, ELQ-300, and combination therapy consisting of ATV plus ELQ-300 (ATV:ELQ-300), using P. yoelii murine models of malaria. In our monotherapy assessments, we found that ATV functioned as a single-dose curative compound in suppressive tests whereas ELQ-300 demonstrated a unique cumulative dosing effect that successfully blocked recrudescence even in a high-parasitemia acute infection model. ATV:ELQ-300 therapy was highly synergistic, and the combination was curative with a single combined dose of 1 mg/kg of body weight. Compared to the ATV:proguanil (Malarone) formulation, ATV:ELQ-300 was more efficacious in multiday, acute infection models and was equally effective at blocking the emergence of ATV-resistant parasites. Ultimately, our data suggest that dual-site inhibition of cyt bc1 is a valuable strategy for antimalarial combination therapy and that Qi site inhibitors such as ELQ-300 represent valuable partner drugs for the clinically successful Qo site inhibitor ATV. PMID:27270285

Repaglinide/troglitazone combination therapy: improved glycemic control in type 2 diabetes.

PubMed

Raskin, P; Jovanovic, L; Berger, S; Schwartz, S; Woo, V; Ratner, R

2000-07-01

This multicenter open-label clinical trial compared the efficacy and safety of repaglinide/troglitazone combination therapy, repaglinide monotherapy, and troglitazone monotherapy in type 2 diabetes that had been inadequately controlled by sulfonylureas, acarbose, or metformin alone. Patients with type 2 diabetes (n = 256) who had inadequate glycemic control (HbA1c > or =7.0%) during previous monotherapy were randomly assigned to receive repaglinide (0.5-4.0 mg at meals), troglitazone (200-600 mg once daily), or a combination of repaglinide (1-4 mg at meals) and troglitazone (200-600 mg once daily). After a 4-6 week washout period, the trial assessed 22 weeks of treatment: 3 weeks (weeks 0-2) of forced titration, 11 weeks of fixed-dose treatment (weeks 3-13), and 8 weeks (weeks 14-21) of titration to maximum dose. Changes in HbA1c and fasting plasma glucose (FPG) values were measured. The combination therapy showed a significant reduction in mean HbA1c values (-1.7%) that was greater than with either type of monotherapy Repaglinide monotherapy resulted in a reduction of HbA1c values that was significantly greater than troglitazone (-0.8 vs. -0.4%) (P < 0.05). Combination therapy was more effective in reducing FPG values (-80 mg/dl) than either repaglinide (-43 mg/dl) or troglitazone (-46 mg/dl) monotherapies. Adverse events were similar in all groups. Combination therapy with repaglinide and troglitazone leads to better glycemic control than monotherapy with either agent alone. Repaglinide monotherapy was more effective in lowering HbA1c levels than troglitazone monotherapy Repaglinide/troglitazone combination therapy was effective and did not show unexpected adverse events.

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

PubMed

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

2017-03-01

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

Induction of Early Autophagic Process on Leishmania amazonensis by Synergistic Effect of Miltefosine and Innovative Semi-synthetic Thiosemicarbazone

PubMed Central

Scariot, Débora B.; Britta, Elizandra A.; Moreira, Amanda L.; Falzirolli, Hugo; Silva, Cleuza C.; Ueda-Nakamura, Tânia; Dias-Filho, Benedito P.; Nakamura, Celso V.

2017-01-01

Drug combination therapy is a current trend to treat complex diseases. Many benefits are expected from this strategy, such as cytotoxicity decrease, retardation of resistant strains development, and activity increment. This study evaluated in vitro combination between an innovative thiosemicarbazone molecule – BZTS with miltefosine, a drug already consolidated in the leishmaniasis treatment, against Leishmania amazonensis. Cytotoxicity effects were also evaluated on macrophages and erythrocytes. Synergistic antileishmania effect and antagonist cytotoxicity were revealed from this combination therapy. Mechanisms of action assays were performed in order to investigate the main cell pathways induced by this treatment. Mitochondrial dysfunction generated a significant increase of reactive oxygen and nitrogen species production, causing severe cell injuries and promoting intense autophagy process and consequent apoptosis cell death. However, this phenomenon was not strong enough to promote dead in mammalian cell, providing the potential selective effect of the tested combination for the protozoa. Thus, the results confirmed that drugs involved in distinct metabolic routes are promising agents for drug combination therapy, promoting a synergistic effect. PMID:28270805

Postictal ventricular tachycardia after electroconvulsive therapy treatment associated with a lithium-duloxetine combination.

PubMed

Heinz, Boeker; Lorenzo, Perniola; Markus, Risch; Holger, Himmighoffen; Beatrix, Roemer; Erich, Seifritz; Alain, Borgeat

2013-09-01

This report addresses the dilemma of continuing lithium prophylaxis and antidepressant therapy in view of cardiovascular adverse effects under electroconvulsive therapy (ECT) in patients with a long history of recurrent affective disorders. A severely depressed 48-year-old woman who had been treated with lithium for 18 years developed a ventricular tachycardia during ECT. Possible interaction with succinylcholine was taken into account, and rocuronium was used as an alternative muscle relaxant. Electroconvulsive therapy was continued without adverse effects after reduction of lithium and withdrawal from duloxetine. Systemic studies on cardiac adverse effects of serotonin and norepinephrine reuptake inhibitors and serotonin and norepinephrine reuptake inhibitor-lithium combinations during ECT are needed.

Natural compounds and combination therapy in colorectal cancer treatment.

PubMed

Rejhová, A; Opattová, A; Čumová, A; Slíva, D; Vodička, P

2018-01-20

Colorectal cancer (CRC) therapy using conventional chemotherapeutics represents a considerable burden for the patient's organism because of high toxicity while the response is relatively low. Our review summarizes the findings about natural compounds as chemoprotective agents for decreasing risk of CRC. It also identifies natural compounds which possess anti-tumor effects of various characteristics, mainly in vitro on colorectal cell lines or in vivo studies on experimental models, but also in a few clinical trials. Many of natural compounds suppress proliferation by inducing cell cycle arrest or induce apoptosis of CRC cells resulting in the inhibition of tumor growth. A novel employment of natural substances is a so-called combination therapy - administration of two or more substances - conventional chemotherapeutics and a natural compound or more natural compounds at a time. Some natural compounds may sensitize to conventional cytotoxic therapy, reinforce the drug effective concentration, intensify the combined effect of both administered therapeutics or exert cytotoxic effects specifically on tumor cells. Moreover, combined therapy by targeting multiple signaling pathways, uses various mechanisms to reduce the development of resistance to antitumor drugs. The desired effect could be to diminish burden on the patient's organism by replacing part of the dose of a conventional chemotherapeutic with a natural substance with a defined effect. Many natural compounds are well tolerated by the patients and do not cause toxic effects even at high doses. Interaction of conventional chemotherapeutics with natural compounds introduces a new aspect in the research and therapy of cancer. It could be a promising approach to potentially achieve improvements, while minimizing of adverse effects associated with conventional chemotherapy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Monotherapy versus combination therapy against carbapenem-resistant Gram-negative bacteria: A retrospective observational study.

PubMed

Ghafur, A; Devarajan, V; Raja, T; Easow, J; Raja, M A; Sreenivas, S; Ramakrishnan, B; Raman, S G; Devaprasad, D; Venkatachalam, B; Nimmagadda, R

2016-01-01

Colistin-based combination therapy (CCT) is extensively used to treat infections due to carbapenem-resistant Gram-negative bacteria (CRGNB). There are no data available from India on the usefulness of combination therapy, especially in the oncology setup. The aim of this study was to analyze the clinical effectiveness of CCT over monotherapy in patients with CRGNB. We conducted a retrospective, observational study of patients with CRGNB bloodstream infections in our oncology and bone marrow transplant center. Over a 3-year study period (2011-2014), we could identify 91 patients satisfying study criteria. There was no statistically significant difference in the 28-day mortality between monotherapy and combination therapy arms (mono n = 26, mortality 10 (38.5%); combination n = 65, mortality 28 (40%); P = 0.886). Neutropenic patients with Enterobacteriaceae bloodstream infections performed better with combination therapy (mono n = 7, mortality 6 (85.7%); combination therapy n = 22, mortality 8 (36.4%); P = 0.035). There was no significant difference in the 28-day mortality between the two treatment arms in other subgroups. Our study did not find CCT superior to colistin monotherapy in patients with CRGNB blood stream infections; except in the subgroup of neutropenic patients with Enterobacteriaceae bloodstream infections, where combination therapy performed better.

The Effect of Ezetimibe/Statin Combination and High-Dose Statin Therapy on Thyroid Autoimmunity in Women with Hashimoto's Thyroiditis and Cardiovascular Disease: A Pilot Study.

PubMed

Krysiak, R; Szkróbka, W; Okopień, B

2016-10-01

Background: Intensive statin therapy was found to reduce thyroid autoimmunity in women with Hashimoto's thyroiditis. No similar data are available for other hypolipidemic agents. Methods: The participants of the study were 16 women with Hashimoto's thyroiditis and coronary artery disease. On the basis of statin tolerance, they were divided into 2 groups. 8 patients who did not tolerate high-dose statin therapy were treated with a statin, the dose of which was reduced by half, together with ezetimibe. The remaining 8 patients tolerating the treatment continued high-dose statin therapy. Plasma lipids, serum levels of thyrotropin, free thyroxine and free triiodothyronine, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later. Results: Replacing high-dose statin therapy with ezetimibe/statin combination therapy increased serum titers of thyroid peroxidase as well as led to an insignificant increase in serum titers of thyroglobulin antibodies. At the end of the study, thyroid peroxidase and thyroglobulin antibody titers were higher in patients receiving the combination therapy than in those treated only with high-dose statin. Conclusions: Our study shows that high-dose statin therapy produces a stronger effect on thyroid autoimmunity than ezetimibe/statin combination therapy. © Georg Thieme Verlag KG Stuttgart · New York.

[Synergistic effect of cell kinetics-directed chemo-endocrine therapy on experimental mammary tumors].

PubMed

Ueki, H

1987-11-01

We tried to demonstrate that the cell kinetics-directed chemoendocrine therapy is more effective on hormone dependent breast cancer than empirical combination of the endocrine therapy and chemotherapy. Cell kinetics of each tumor was measured by flow cytometric analysis. Estrogen dependent human breast cancer cell line MCF-7 was used in vitro. In vivo, androgen dependent SC-115 carcinoma was transplanted to DDS mice. In vitro, tamoxifen was administered as the endocrine therapy. In vivo, we carried out testectomy on DDS mice. Effect of the endocrine therapy on the cell kinetics of the tumor was thought to be G1-S depression. High density 5FU was administered as the chemotherapeutic agents, whose content was 1 microgram/ml in vitro and 40 mg/kg in vivo. 5FU brought temporary decrease of cells in S phase. Only anteceding 5FU administration had synergistic effect in combination of 5FU and the endocrine therapy. 5FU was convinced to act more effectively on cells in S phase, so it was shown that cell kinetics-directed schedule was superior to the empirical treatment schedule in chemoendocrine therapy.

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

PubMed

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

2017-06-01

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

[Flying needling therapy combined with clomiphene for ovulation failure in polycystic ovary syndrome:a randomized controlled trial].

PubMed

Ma, Hong; Quan, Xiaohong; Chen, Xiuhua; Dong, Ying

2016-11-12

To compare the efficacy among the combined treatment of flying needling therapy and clomiphene, the simple application of flying needling therapy and simple clomiphene in the treatment of ovulation failure in polycystic ovary syndrome (PCOS). Ninety patients of PCOS were randomized into a flying needling therapy group, a medication group and a combined treatment group, 30 cases in each one. In the flying needling therapy group, the flying needling therapy was simply applied to Ganshu (BL 18), Shenshu (BL 23), Zhongwan (CV 12), Shuifen (CV 9), Guanyuan (CV 4) and Zhongji (CV 3). The unilateral back- shu points were used alternatively in each treatment. The needles were inserted rapidly with rotation technique and even-needling manipulation. The needles were retained for 30 min. The treatment was given once every two days, 3 times a week. In the medication group, clomiphene was taken orally on the 5th day of menstruation, continuously for 5 days. In the combined treatment group, the flying needling therapy and clomiphene were used in combination. All of the patients were treated for 3 months and followed up for 1 month. The ovulation rates were compared among the three groups. The levels of androgen testosterone were compared before and after treatment. In the combined treatment group, the ovulation rate was 86.2% (100/116), better than 66.7% (80/120) in the flying needling therapy group and 69.6% (78/112) in the medication group (both P <0.05). The efficacy was similar between the fly needling therapy group and the medication group ( P >0.05). After treatment, the level of testosterone was reduced in the three groups (all P <0.05). In the combined treatment group, the improvement in androgen level was better than those in the flying needling therapy group and the medication group (both P <0.05). The efficacy was similar between the flying needling therapy group and the medication group ( P >0.05). The adverse reactions in the combined treatment group and the flying needling therapy group were lower than those in the medication group (both P <0.05). The flying needling therapy effectively improves in the ovulation failure of PCOS and its effect is similar to clomiphene. The allied treatment of them apparently improves the clinical efficacy and alleviates the adverse reactions.

Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats.

PubMed

Refaat, Rowaida; Salama, Mona; Abdel Meguid, Elham; El Sarha, Ashgan; Gowayed, Mennatallah

2013-01-05

There is increasing body of evidence documenting the involvement of angiotensin II in inflammatory diseases. Moreover the up-regulation of angiotensin II AT(1) receptors in the synovium of rheumatoid arthritis patients has been previously described. This study aimed at investigating the anti-inflammatory effect of losartan, the selective angiotensin II AT(1) receptor blocker, and comparing the efficacy of methotrexate alone and in combination with losartan in adjuvant arthritis in rats. Twelve days post adjuvant injection, Sprague-Dawley rats were treated with methotrexate (1mg/kg/week), losartan (20mg/kg/day) and their combination for 15 days. Severity of arthritis was assessed by hind paw swelling, arthrogram scores. Serum was analyzed for measurement of albumin, C-reactive protein (CRP), nitrite/nitrate concentrations, interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), aspartate transaminase (AST) and alanine transaminase (ALT). Histopathological examination was done for hind paws and livers. Methotrexate and losartan monotherapies significantly reduced all parameters of inflammation and arthritis with better results in the methotrexate group except for the transaminases where losartan caused more significant reduction in their serum levels. The combined therapy showed better results than methotrexate and losartan alone. Hind paws showed better improvement of inflammatory cell infiltration and bone resorption in the combined therapy group. Disturbances in liver architecture and fibrosis caused by adjuvant arthritis were reverted to normal status in the combined therapy group in contrast to losartan and methotrexate monotherapies. In conclusion, methotrexate and losartan combined therapy provided more effective anti-inflammatory and hepatoprotective effects than either drug alone. Copyright © 2012 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-06-01

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

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

PubMed Central

2012-01-01

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

Effective Treatment of Advanced Human Melanoma Metastasis in Immunodeficient Mice Using Combination Metronomic Chemotherapy Regimens

PubMed Central

Cruz-Munoz, William; Man, Shan; Kerbel, Robert S.

2009-01-01

Statement of translational relevance Despite significant efforts over the last two decades aimed at improving the efficacy of standard treatment (maximum tolerated dose (MTD) of dacarbazine), there has been no significant increase in the median survival of patients suffering from metastatic melanoma. Given the lack of success achieved, a rethinking of alternative treatment strategies is needed. Using preclinical models of advanced melanoma metastasis, we show that metronomic chemotherapeutic combinations results in improved survival, which is achieved with minimal toxicity. These results compare favorably with minimal effectiveness achieved by MTD dacarbazine therapy (alone or in combination with other chemotherapeutic agents or a VEGFR-blocking antibody), often accompanied by higher toxicity. Successes in preclinical setting of metastatic breast cancer have led to a clinical trial to examine the efficacy of metronomic therapy. A similar extension of the metronomic chemotherapeutic combinations presented here into the clinical setting of melanoma metastasis may be warranted. Purpose The development of effective therapeutic approaches for treatment of metastatic melanoma remains an immense challenge. Present therapies offer minimal benefit. While dacarbazine (DTIC) chemotherapy remains the standard therapy, it mediates only low response rates, usually of short duration, even when combined with other chemotherapeutic agents. Thus, new therapeutic strategies are urgently needed. Experimental design Using a newly developed preclinical model, we evaluated the efficacy of various doublet metronomic combination chemotherapy against established, advanced melanoma metastasis and compared these to the standard maximum tolerated dose (MTD) DTIC (alone or in combination with chemotherapeutic agents or VEGFR-blocking antibody) Results Whereas MTD DTIC therapy did not cause significant improvement in median survival, a doublet combination of low-dose metronomic (LDM) vinblastine (Vbl) and LDM cyclophosphamide (CTX) induced a significant increase in survival with only minimal toxicity. Furthermore, we show that the incorporation of the LDM Vbl/LDM CTX combination with a LDM DTIC regimen also results in a significant increase in survival, but not when combined with MTD DTIC therapy. We also show that a combination of metronomic Vbl therapy and a VEGFR2-blocking antibody (DC101) results in significant control of metastatic disease and that the combination of LDM Vbl/DC101 and LDM DTIC induced a significant improvement in median survival. Conclusions The effective control of advanced metastatic melanoma achieved by these metronomic-based chemotherapeutic approaches warrants clinical consideration of this treatment concept given the recent results of a number of metronomic-based chemotherapy clinical trials. PMID:19622578

The novel language-systematic aphasia screening SAPS: screening-based therapy in combination with computerised home training.

PubMed

Krzok, Franziska; Rieger, Verena; Niemann, Katharina; Nobis-Bosch, Ruth; Radermacher, Irmgard; Huber, Walter; Willmes, Klaus; Abel, Stefanie

2018-03-01

SAPS-'Sprachsystematisches Aphasiescreening'-is a novel language-systematic aphasia screening developed for the German language, which already had been positively evaluated. It offers a fast assessment of modality-specific psycholinguistic components at different levels of complexity and the derivation of impairment-based treatment foci from the individual performance profile. However, SAPS has not yet been evaluated in combination with the new SAPS-based treatment. To replicate the practicality of SAPS and to investigate the effectiveness of a SAPS-based face-to-face therapy combined with computerised home training in a feasibility study. To examine the soundness of the treatment design, to determine treatment-induced changes in patient performance as measured by SAPS, to assess parallel changes in communicative abilities, and to differentiate therapy effects achieved by face-to-face therapy versus add-on effects achieved by later home training. Sixteen participants with post-stroke aphasia (PWAs) were included into the study. They were administered the SAPS and communicative testing before and after the treatment regimen. Each PWA received one therapy session followed by home training per day, with the individual treatment foci being determined according to initial SAPS profile, and duration of treatment and possible change of focus dependent on performance assessed by continuous therapy monitoring. The combination of therapy and home training based on the SAPS was effective for all participants. We showed significant improvements for impairment-based SAPS performance and, with high inter-individual variability, in everyday communication. These two main targets of speech and language therapy were correlated and SAPS improvements after therapy were significantly higher than after home training. SAPS offers the assessment of an individual performance profile in order to derive sufficiently diversified, well-founded and specific treatment foci and to follow up changes in performance. The appending treatment regimen has shown to be effective for our participants. Thus, the study revealed feasibility of our approach. © 2017 Royal College of Speech and Language Therapists.

The therapeutic advantage of combination antihypertensive drug therapy using amlodipine and irbesartan in hypertensive patients: Analysis of the post-marketing survey data from PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; safety and efficacy in patients with hypertension) study.

PubMed

Ishimitsu, Toshihiko; Fukuda, Hirofumi; Uchida, Masako; Ishibashi, Kazushi; Sato, Fusako; Nukui, Kazuhiko; Nagao, Munehiko

2015-01-01

Two-thirds of hypertensive patients need a combination antihypertensive therapy to achieve the target blood pressure (BP). The PARTNER (Practical combination therapy of Amlodin and angiotensin II Receptor blocker; Safety and efficacy in paTieNts with hypERtension) study is a prospective specific clinical use survey examining the efficacy and safety of 12-week treatment with amlodipine (AML) and Angiotensin II Receptor Blocker (ARB) in 5900 hypertensive patients. The current analysis was performed as to the BP control, adverse reactions, and the effects on laboratory data in patients treated with the combination of AML and irbesartan (IRB), namely the patients added AML to already taking IRB (AML add-on group, n = 1202) and the patients added IRB to AML (IRB add-on group, n = 1050). Both study groups showed distinct decreases in office BP at 4 week (p < 0.001) and the antihypertensive effects were sustained to 12 week (p < 0.001). The percentage of patients achieving BP < 140/90 mmHg was ∼70% in either group. Proteinuria and estimated glomerular filtration rate (eGFR) were significantly improved in hypertensive patients with baseline eGFR <60 ml/min/1.73 m(2). Serum uric acid was reduced either by adding AML or IRB, and the reductions were prominent in patients with serum uric acid >7 mg/dl. The incidence of adverse reactions was as few as 1.11% and there were no severe adverse reactions which hampered the continuation of combination therapy. In conclusion, combination antihypertensive therapy with AML and IRB effectively lowers BP without particular safety problems, reduces serum uric acid especially in patients with hyperuricemia and exhibits renoprotective effects in patients with chronic kidney disease.

[Treatment strategy of type 2 diabetes used in Czech Republic after metformin therapy failure].

PubMed

Svačina, Štěpán; Ovesná, Petra; Kuhn, Matyáš; Nováčková, Martina

Type 2 diabetes is an enormous medical problem caused by increasing prevalence of the disease and increasing prevalence of severe chronic complications of diabetes. New ADA/EASD guidelines and also Czech diabetes society guidelines enable effective individual approach to the patient. Goal of the therapy is optimal compensation of diabetes and prevention of acute and chronic complications of diabetes and decrease of mortality. Diabetes therapy is started by education in diet a regime combined with metformin. According to the progressive character of the disease it is usually necessary to intensify the therapy by adding antidiabetics from other groups. This study was proposed to analyse the use of therapy algorithm in Czech Republic in patients with insufficient metformin therapy. Secondary objectives were to describe level of compensation of diabetes in time and level of components of the metabolic syndrome in different treatment combinations.Methodic and results: In the sample of 1 516 patients, frequency of use of antidiabetic medication after metformin it was gliflozins 33% and gliptins 28% in the first phase of the study and the number increased later during the study. Median of HbA1c in the beginning of the study was 65 mmol/mol, greatest decrease was found in patents using combination of incretine analogs with metformin - 89 % of them had the HbA1c level < 60 mmol/mol. The study showed also that antidiabetic drugs used after metformin in Czech Republic are very effective in reducing weight, and improving blood pressure and lipid profile. Therapy using combination of metformin with gliflozins, gliptins or incretin analogs is most effective when metformin is not effective enough.Key words: diabetes type 2 - gliflozins - gliptins - incretine analogs - metformin therapy failure.

Combination therapy for malaria in Africa: hype or hope?

PubMed Central

Bloland, P. B.; Ettling, M.; Meek, S.

2000-01-01

The development of resistance to drugs poses one of the greatest threats to malaria control. In Africa, the efficacy of readily affordable antimalarial drugs is declining rapidly, while highly efficacious drugs tend to be too expensive. Cost-effective strategies are needed to extend the useful life spans of antimalarial drugs. Observations in South-East Asia on combination therapy with artemisinin derivatives and mefloquine indicate that the development of resistance to both components is slowed down. This suggests the possibility of a solution to the problem of drug resistance in Africa, where, however, there are major obstacles in the way of deploying combination therapy effectively. The rates of transmission are relatively high, a large proportion of asymptomatic infection occurs in semi-immune persons, the use of drugs is frequently inappropriate and ill-informed, there is a general lack of laboratory diagnoses, and public health systems in sub-Saharan Africa are generally weak. Furthermore, the cost of combination therapy is comparatively high. We review combination therapy as used in South-East Asia and outline the problems that have to be overcome in order to adopt it successfully in sub-Saharan Africa. PMID:11196485

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

PubMed

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

2016-06-06

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

Immune Effects of Chemotherapy, Radiation, and Targeted Therapy and Opportunities for Combination With Immunotherapy.

PubMed

Wargo, Jennifer A; Reuben, Alexandre; Cooper, Zachary A; Oh, Kevin S; Sullivan, Ryan J

2015-08-01

There have been significant advances in cancer treatment over the past several years through the use of chemotherapy, radiation therapy, molecularly targeted therapy, and immunotherapy. Despite these advances, treatments such as monotherapy or monomodality have significant limitations. There is increasing interest in using these strategies in combination; however, it is not completely clear how best to incorporate molecularly targeted and immune-targeted therapies into combination regimens. This is particularly pertinent when considering combinations with immunotherapy, as other types of therapy may have significant impact on host immunity, the tumor microenvironment, or both. Thus, the influence of chemotherapy, radiation therapy, and molecularly targeted therapy on the host anti-tumor immune response and the host anti-host response (ie, autoimmune toxicity) must be taken into consideration when designing immunotherapy-based combination regimens. We present data related to many of these combination approaches in the context of investigations in patients with melanoma and discuss their potential relationship to management of patients with other tumor types. Importantly, we also highlight challenges of these approaches and emphasize the need for continued translational research. Copyright © 2015 Elsevier Inc. All rights reserved.

Synergizing Radiation Therapy and Immunotherapy for Curing Incurable Cancers: Opportunities and Challenges

PubMed Central

Hodge, James W.; Guha, Chandan; Neefjes, Jacques; Gulley, James L.

2012-01-01

The combination of radiation therapy and immunotherapy holds particular promise as a strategy for cancer therapeutics. There is evidence that immunotherapy is most beneficial alone when employed early in the disease process or in combination with standard therapies (e.g., radiation) later in the disease process. Indeed, radiation may act synergistically with immunotherapy to enhance immune responses, inhibit immunosuppression, and/or alter the phenotype of tumor cells, thus rendering them more susceptible to immune-mediated killing. Furthermore, as monotherapies, both immunotherapy and radiation may be insufficient to eliminate tumor masses. However, following immunization with a cancer vaccine, the destruction of even a small percentage of tumor cells by radiation could result in cross-priming and presentation of tumor antigens to the immune system, thereby potentiating antitumor responses. Learning how to exploit radiation-induced changes to tumor-cell antigens, and how to induce effective immune responses to these cumulatively immunogenic stimuli, is an exciting frontier in cancer therapy research. This review examines a) mechanisms by which many forms of radiation therapy can induce or augment antitumor immune responses and b) preclinical systems that demonstrate that immunotherapy can be effectively combined with radiation therapy. Finally, we review current clinical trials where standard-of-care radiation therapy is being combined with immunotherapy. PMID:18777956

[How to Increase the Effectiveness of Antihypertensive Therapy in Clinical Practice: Results of the Russian Observational Program FORSAZH].

PubMed

Glezer, M G; Deev On Behalf Of The Participants Of The Program, A D

2016-01-01

im of the study - to evaluate the possibility of increasing the effectiveness of antihypertensive therapy by simplifying regimens, improving knowledge and practical skills of the doctors on the use of modern tactical approaches to treatment as well as patients education methods of measuring blood pressure (BP), the principles of a healthy lifestyle and explain the need to follow the prescribing physician. Post-marketing observational discovery program FORSAZH held in 29 cities of the Russian Federation. Participation in the program received 442 physician (internists and general practitioners), which included 1969 patients with prior failure of combination antihypertensive therapy. Patients in 86% of cases took the free combination, 14% - fixed combinations of drugs. The change of the treatment on reception of a preparation containing a fixed combination of perindopril/indapamide (10 mg/2.5 mg) after 3 months led to decrease in systolic blood pressure by an average of 39.5 mm Hg, diastolic - 18.7 per mm Hg. The frequency of achieving the target BP <140 mm Hg and 90 it was 76%. Marked reduction in BP and frequency to achieve the target BP is not dependent on additional training of physicians and patients, the use of prior therapy in free or fixed combination, but depended on the initial degree of increase in BP and duration of therapy. Predictors of failure to achieve target BP were age, male gender, low initial adherence, good health, a higher baseline BP, elevated cholesterol levels, body weight, heart rate and decreased glomerular filtration rate. Adherence to therapy patients (on a scale of Morisky-Green) and health assessment on a visual analog scale significantly increased. This tactic has been a change of therapy is not only effective but also safe. Adverse events were reported in 28 patients (1.4% of the total number of observed cases) and only 1 case required dose reduction due to development of clinically manifested hypotension. In enhancing the effectiveness of the treatment of patients with hypertension was decisive simplification of drug therapy through the use of a fixed combination of perindopril A/indapamide.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.

PubMed

Koonce, Nathan A; Quick, Charles M; Hardee, Matthew E; Jamshidi-Parsian, Azemat; Dent, Judith A; Paciotti, Giulio F; Nedosekin, Dmitry; Dings, Ruud P M; Griffin, Robert J

2015-11-01

Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose-notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation therapy is effective in reducing IFP and tumor growth and shows promise for clinical translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Modeling the effects of space structure and combination therapies on phenotypic heterogeneity and drug resistance in solid tumors.

PubMed

Lorz, Alexander; Lorenzi, Tommaso; Clairambault, Jean; Escargueil, Alexandre; Perthame, Benoît

2015-01-01

Histopathological evidence supports the idea that the emergence of phenotypic heterogeneity and resistance to cytotoxic drugs can be considered as a process of selection in tumor cell populations. In this framework, can we explain intra-tumor heterogeneity in terms of selection driven by the local cell environment? Can we overcome the emergence of resistance and favor the eradication of cancer cells by using combination therapies? Bearing these questions in mind, we develop a model describing cell dynamics inside a tumor spheroid under the effects of cytotoxic and cytostatic drugs. Cancer cells are assumed to be structured as a population by two real variables standing for space position and the expression level of a phenotype of resistance to cytotoxic drugs. The model takes explicitly into account the dynamics of resources and anticancer drugs as well as their interactions with the cell population under treatment. We analyze the effects of space structure and combination therapies on phenotypic heterogeneity and chemotherapeutic resistance. Furthermore, we study the efficacy of combined therapy protocols based on constant infusion and bang-bang delivery of cytotoxic and cytostatic drugs.

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PubMed

Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

2017-12-01

The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

[Spasmodic hemiplegia after stroke treated with scalp acupuncture, music therapy and rehabilitation: a randomized controlled trial].

PubMed

Jia, Chengjie; Zhang, Hongru; Ni, Guangxia; Zhang, Yinan; Su, Bin; Xu, Xinlei

2017-12-12

To evaluate the differences in the clinical therapeutic effects on spasmodic hemiplegia after stroke among the alliance therapy of scalp acupuncture, music therapy combined with rehabilitation, the simple rehabilitation therapy and the combination of music therapy and rehabilitation. A total of 76 patients of post-stroke spasmodic hemiplegia were randomized into a rehabilitation group (25 cases), a combination group with music therapy and rehabilitation (25 cases) and an alliance therapy group with scalp acupuncture, music therapy and rehabilitation (26 cases). In the rehabilitation group, the routine rehabilitation therapy was applied, including the removal of various incentives that cause spasm, the correction of body position and the physical therapy. In the combination group, the music therapy was added on the basis of the treatment as the rehabilitation group. The music physician used the rhythmic auditory stimulation, the patterned sensory enhancement and the therapeutic instrumental music playing to set up the task in the treatment. In the alliance therapy group, scalp acupuncture was added on the basis of the treatment as the combination group. The anterior oblique line of vertex-tempora (MS 6) and the posterior oblique line of vertex-tempora (MS 7) on the contralateral side were selected and stimulated with penetrating needling technique. The needles were retained. During the needling retaining, the needles were rotated once every 10 min, for 2 min each time. The treatment was given one session a day, totally for 5 sessions a week, continuously for 4 weeks. The Fugl-Meyer assessment (FMA), Barthel index (BI) and the modified Ashworth scale (MAS) of the affected elbow and the passive knee movement at static condition were observed in the patients before and after treatment. The results of FMA, BI and MAS were not different before treatment in the patients among the three groups (all P >0.05), indicating the comparability among groups. After treatment, FMA and BI scores were all increased apparently in the three groups as compared with those before treatment (all P <0.05). MAS grade was reduced remarkably as compared with that before treatment (all P <0.05). After treatment, FMA and BI scores in the alliance therapy group were higher than those in the combination group and the rehabilitation group (all P <0.05). FMA and BI scores in the combination group were higher than those in the rehabilitation group (both P <0.05). MAS grade in the alliance therapy group was lower than those in the combination group and the rehabilitation group (both P <0.05). MAS grade in the combination group was lower than that in the rehabilitation group ( P <0.05). The alliance therapy with scalp acupuncture, music therapy and rehabilitation achieve the remarkable clinical therapeutic effects on post-stroke spasmodic hemiplegia as compared with the routine rehabilitation and the combination of music therapy and rehabilitation.

Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

PubMed Central

Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel

2014-01-01

There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131

A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor

NASA Astrophysics Data System (ADS)

Chen, Yu-Wei; Liu, Tse-Ying; Chang, Po-Hsueh; Hsu, Po-Hung; Liu, Hao-Li; Lin, Hong-Cheu; Chen, San-Yuan

2016-06-01

Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor.Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr07782f

Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes.

PubMed

Vora, J; Bain, S C; Damci, T; Dzida, G; Hollander, P; Meneghini, L F; Ross, S A

2013-02-01

Incretin therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4Is) and GLP-1 receptor agonists (GLP-1RAs) have become well-established treatments for type 2 diabetes. Both drug classes reduce blood glucose through physiological pathways mediated by the GLP-1 receptor, resulting in glucose-dependent enhancement of residual insulin secretion and inhibition of glucagon secretion. In addition, the GLP-1RAs reduce gastrointestinal motility and appear to have appetite-suppressing actions and, so, are often able to produce clinically useful weight loss. The glucose-dependency of their glucagon-inhibiting and insulin-enhancing effects, together with their weight-sparing properties, make the incretin therapies a logical proposition for use in combination with exogenous basal insulin therapy. This combination offers the prospect of an additive or synergistic glucose-lowering effect without a greatly elevated risk of hypoglycaemia compared with insulin monotherapy, and any insulin-associated weight gain might also be mitigated. Furthermore, the incretin therapies can be combined with metformin, which is usually continued when basal insulin is introduced in type 2 diabetes. Although the combination of incretin and insulin therapy is currently not addressed in internationally recognized treatment guidelines, several clinical studies have assessed its use. The data, summarized in this review, are encouraging and show that glycaemic control is improved and weight gain is limited or reversed (especially with the combined use of GLP-1RAs and basal insulin), and that the use of an incretin therapy can also greatly reduce insulin dose requirements. The addition of basal insulin to established incretin therapy is straightforward, but insulin dose adjustment (though not discontinuation) is usually necessary if the sequence is reversed. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Combination Therapy of LysGH15 and Apigenin as a New Strategy for Treating Pneumonia Caused by Staphylococcus aureus

PubMed Central

Xia, Feifei; Li, Xin; Wang, Bin; Gong, Pengjuan; Xiao, Feng; Yang, Mei; Zhang, Lei; Song, Jun; Hu, Liyuan; Cheng, Mengjun; Sun, Changjiang; Feng, Xin; Lei, Liancheng; Ouyang, Songying; Liu, Zhi-Jie; Li, Xinwei

2015-01-01

Pneumonia is one of the most prevalent Staphylococcus aureus-mediated diseases, and the treatment of this infection is becoming challenging due to the emergence of multidrug-resistant S. aureus, especially methicillin-resistant S. aureus (MRSA) strains. It has been reported that LysGH15, the lysin derived from phage GH15, displays high efficiency and a broad lytic spectrum against MRSA and that apigenin can markedly diminish the alpha-hemolysin of S. aureus. In this study, the combination therapy of LysGH15 and apigenin was evaluated in vitro and in a mouse S. aureus pneumonia model. No mutual adverse influence was detected between LysGH15 and apigenin in vitro. In animal experiments, the combination therapy showed a more effective treatment effect than LysGH15 or apigenin monotherapy (P < 0.05). The bacterial load in the lungs of mice administered the combination therapy was 1.5 log units within 24 h after challenge, whereas the loads in unprotected mice or mice treated with apigenin or LysGH15 alone were 10.2, 4.7, and 2.6 log units, respectively. The combination therapy group showed the best health status, the lowest ratio of wet tissue to dry tissue of the lungs, the smallest amount of total protein and cells in the lung, the fewest pathological manifestations, and the lowest cytokine level compared with the other groups (P < 0.05). With regard to its better protective efficacy, the combination therapy of LysGH15 and apigenin exhibits therapeutic potential for treating pneumonia caused by MRSA. This paper reports the combination therapy of lysin and natural products derived from traditional Chinese medicine. PMID:26475103

Combination therapy using intratumoral bacillus Calmette-Guerin (BCG) and vincristine in dogs with transmissible venereal tumours: therapeutic efficacy and histological changes.

PubMed

Mukaratirwa, S; Chitanga, S; Chimatira, T; Makuleke, C; Sayi, S T; Bhebhe, E

2009-06-01

Therapeutic efficacy and histological changes after bacillus Calmette-Guerin (BCG), vincristine and BCG/vincristine combination therapy of canine transmissible venereal tumours (CTVT) were studied. Twenty dogs with naturally occurring CTVT in the progression stage were divided into 4 groups and treated with intratumoral BCG, vincristine, BCG/vincristine combination therapy or intratumoral buffered saline (control group). Tumour sizes were determined weekly and tumour response to therapy was assessed. Tumour biopsies were taken weekly to evaluate histological changes. Complete tumour regression was observed in all the dogs treated with BCG, vincristine and BCG/vincristine combination therapy. BCG/vincristine combination therapy had a statistically significantly shorter regression time than BCG or vincristine therapy. No tumour regression was observed in the control group. Intratumoral BCG treatment resulted in the appearance of macrophages and increased numbers of tumour infiltrating lymphocytes (TILs) followed by tumour cell apoptosis and necrosis. Treatment with vincristine resulted in increased tumour cell apoptosis, reduction in the mitotic index and a decrease in the number of TILs. Tumours from dogs on BCG/vincristine combination were characterised by reduction in the mitotic index, and appearance of numerous TILs and macrophages followed by marked tumour cell apoptosis and necrosis. This study indicates that combined BCG and vincristine therapy is more effective than vincristine in treating CTVT, suggesting that the clinical course of this disease may be altered by immunochemotherapy.

Gender-related different effects of a combined therapy of Exenatide and Metformin on overweight or obesity patients with type 2 diabetes mellitus.

PubMed

Quan, Huibiao; Zhang, Huachuan; Wei, Weiping; Fang, Tuanyu

2016-01-01

Although men and women have similar diabetes prevalence, the same medicine will cause different therapeutic results in different genders. To understand the molecular mechanism, we explored the effects of a combined therapy of Exenatide and Metformin on obesity and overweight female and male patients with newly diagnosed type 2 diabetes mellitus (T2DM). One hundred and five overweight and obesity patients with newly diagnosed T2DM (n=54 female in a female group and n=51 males in a male group) received the therapy: 5 μg Exenatide+0.5 g MET twice daily for 4 weeks, then 10 μg Exenatide+0.5 g MET twice daily for 24 weeks. There was an average of 8.2 ± 2.4 kg and 4.6 ± 2.3 kg weight loss in female and male patients, respectively. The combined therapy showed better effects on female than male patients for improving insulin sensitivity and serum lipid profile, reducing insulin resistance, increasing adiponectin levels, and decreasing the levels of HbA1c, BMI, resistin, TNF-alpha and C-reactive protein (P<0.05). The combined therapy of Exenatide and MET shows better therapeutic results in female patients than in male patients. Therefore, the dual therapy is more suitable for female patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Combining Pharmacological Countermeasures to Attenuate the Acute Radiation Syndrome-A Concise Review.

PubMed

Hofer, Michal; Hoferová, Zuzana; Depeš, Daniel; Falk, Martin

2017-05-19

The goal of combined pharmacological approaches in the treatment of the acute radiation syndrome (ARS) is to obtain an effective therapy producing a minimum of undesirable side effects. This review summarizes important data from studies evaluating the efficacy of combining radioprotective agents developed for administration prior to irradiation and therapeutic agents administered in a post-irradiation treatment regimen. Many of the evaluated results show additivity, or even synergism, of the combined treatments in comparison with the effects of the individual component administrations. It can be deduced from these findings that the research in which combined treatments with radioprotectors/radiomitigators are explored, tested, and evaluated is well-founded. The requirement for studies highly emphasizing the need to minimize undesirable side effects of the radioprotective/radiomitigating therapies is stressed.

Near-infrared light-responsive nanomaterials in cancer therapeutics.

PubMed

Shanmugam, Vijayakumar; Selvakumar, S; Yeh, Chen-Sheng

2014-09-07

Noninvasive techniques, such as breath tests (urea breath test), blood pressure measurements using a sphygmomanometer and electrocardiography, were employed by a physician to perform classical diagnosis. The use of state-of-the-art noninvasive therapies at the organ level in modern medicine has gradually become possible. However, cancer treatment demands spatially and temporally controlled noninvasive therapy at the cell level because nonspecific toxicity often causes complicated side effects. To increase survival in cancer patients further, combination therapy and combination drugs are explored which demand high specificity to avoid combined-drug side effects. We believe that high specificity could be obtained by implementing near-infrared (NIR) light-assisted nanoparticles in photothermal therapy, chemotherapy, and photodynamic therapy. To refine this therapy and subsequently achieve high efficiency, novel nanomaterials have been designed and modified either to enhance the uptake and drug delivery to the cancer site, or control treatment to administer therapy efficiently. These modifications and developments have been demonstrated to achieve spatial and temporal control when conducting an in vivo xenograft, because the NIR light penetrated effectively the biological tissue. The nanoplatforms discussed in this review are grouped under the following subheadings: Au nanorods (NRs), Au nanoshells, other Au-related nanomaterials, graphene oxide, upconversion nanoparticles, and other related materials (including materials such as CuS, Fe3O4-related systems, and carbon nanotubes (CNTs)).

Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

PubMed

Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

2012-01-01

The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

Effectiveness of Combined Therapy with Pirfenidone and Erythromycin for Unclassifiable Interstitial Pneumonia Induced by HTLV-1-associated Bronchioloalveolar Disorder (HABA)

PubMed Central

Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko

2017-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003

Kinetics of blood lipoprotein spectrum indices in patients with angina pectoris during and after low-intensity laser therapy as a paraclinical criterion for treatment efficiency

NASA Astrophysics Data System (ADS)

Babushkina, G. V.; Kartelishev, A. V.

2001-04-01

An investigation was made of applying (lambda) equals 0.63 micrometers laser radiation in treating 403 patients affected by angina pectoris. The patients were administered a course of combined laser therapy consisting of the intravenous laser irradiation of blood combined with laser acupuncture. Apart from that, the patients took the maintenance doses of antianginal preparations and therapeutic doses of vitamins A and E. The blood lipoprotein spectrum revealed that this combined laser therapy was capable of producing an antiatherogenic effect. It was also found that the most effective exposure time of laser radiation was in the range of 10 to 15 min.

Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study.

PubMed

Briese, Volker; Stammwitz, Ute; Friede, Michael; Henneicke-von Zepelin, Hans-Heinrich

2007-08-20

To evaluate usage pattern, effectiveness and safety of Black cohosh alone or in fixed combination with St. John's wort on menopausal symptoms in general clinical practice. Prospective, controlled open-label observational study of 6141 women at 1287 outpatient gynecologists in Germany. Subjects were treated with recommended doses of study therapies, with treatment chosen by the participating physicians. Patients were followed up for 6 months, optionally 12 months. The primary effectiveness variable was Menopause Rating Scale (MRS) subscore PSYCHE at Month 3 evaluated by ANCOVA. The treatment groups were comparable at baseline, excepting the main MRS score and the PSYCHE score (monotherapy: 0.31+/-0.22; combination therapy: 0.42+/-0.23). Reductions from baseline were seen with both regimens for all variables. The changes in the primary variable remained significantly different between groups (p<0.001) when adjusted for differences at baseline with the combination therapy being superior: from 0.37 (adjusted) to 0.25 (95% CI: 0.24-0.25) and 0.23 (95% CI: 0.22-0.23) at Month 3 in the monotherapy and combination-therapy groups, respectively. The improvement by both therapies was maintained at 6 and 12 months. The rate of possibly treatment-related adverse events was 0.16%, all non-serious. The results support the effectiveness and tolerability profiles of two Black cohosh-based therapies for menopausal symptoms in general practice. They were used differentially: the monotherapy for neurovegetative symptoms, the combination for patients with more pronounced mood complaints. The fixed combination of Black cohosh and St. John's wort was superior to Black cohosh alone in alleviating climacteric mood symptoms.

A versatile nanoplatform for synergistic combination therapy to treat human esophageal cancer.

PubMed

Wang, Xin-Shuai; Kong, De-Jiu; Lin, Tzu-Yin; Li, Xiao-Cen; Izumiya, Yoshihiro; Ding, Xue-Zhen; Zhang, Li; Hu, Xiao-Chen; Yang, Jun-Qiang; Gao, She-Gan; Lam, Kit S; Li, Yuan-Pei

2017-06-01

One of the major goals of precision oncology is to promote combination therapy to improve efficacy and reduce side effects of anti-cancer drugs based on their molecular mechanisms. In this study, we aimed to develop and validate new nanoformulations of docetaxel (DTX) and bortezomib (BTZ) for targeted combination therapy to treat human esophageal cancer. By leveraging our versatile disulfide cross-linked micelles (DCMs) platform, we developed nanoformulations of DTX and BTZ (named DTX-DCMs and BTZ-DCMs). Their physical properties were characterized; their anti-cancer efficacies and mechanisms of action were investigated in a human esophageal cancer cell line in vitro. Furthermore, the in vitro anti-tumor activities of combination therapies (concurrent drug treatment, sequential drug treatment, and treatment using different ratios of the drugs) were examined in comparison with the single drug treatment and free drug strategies. These drug-loaded nanoparticles were spherical in shape and relatively small in size of approximately 20-22 nm. The entrapment efficiencies of DTX and BTZ into nanoparticles were 82.4% and 84.1%, respectively. The drug release rates of DTX-DCMs and BTZ-DCMs were sustained, and greatly increased in the presence of GSH. These nanodrugs were effectively internalized by KYSE30 esophageal cancer cells, and dose-dependently induced cell apoptosis. We further revealed a strong synergistic effect between DTX-DCMs and BTZ-DCMs against KYSE30 esophageal cancer cells. Sequential combination therapy with DTX-DCMs followed by BTZ-DCMs exhibited the best anti-tumor efficacy in vitro. This study demonstrates that DTX and BTZ could be successfully nanoformulated into disulfide cross-linked micelles. The nanoformulations of DTX and BTZ demonstrate an immense potential for synergistic combination therapy to treat human esophageal cancer.

TLR7 agonist in combination with Salmonella as an effective antimelanoma immunotherapy.

PubMed

Vola, Magdalena; Mónaco, Amy; Bascuas, Thais; Rimsky, Geraldine; Agorio, Caroline Isabel; Chabalgoity, José Alejandro; Moreno, María

2018-03-22

We evaluated a novel approach combining the use of attenuated Salmonella immunotherapy with a Toll-like receptor agonist, imiquimod, in B16F1 melanoma-bearing mice. B16F1 melanoma-bearing mice were daily treated with topical imiquimod in combination with one intratumoral injection of attenuated Salmonella enterica serovar Typhimurium LVR01. The combined therapy resulted in retarded tumor growth and prolonged survival. Combination treatment led to an enhancement in the expression of pro-inflammatory cytokines and chemokines in the tumor microenvironment, with a Th1-skewed profile, resulting in a broad antitumor response. The induced immunity was effective in controlling the occurrence of metastasis. Salmonella LVR01 immunotherapy in combination with imiquimod is a novel approach that could be considered as an effective antimelanoma therapy.

Probiotics in Helicobacter pylori eradication therapy: Systematic review and network meta-analysis.

PubMed

Wang, Fan; Feng, Juerong; Chen, Pengfei; Liu, Xiaoping; Ma, Minxing; Zhou, Rui; Chang, Ying; Liu, Jing; Li, Jin; Zhao, Qiu

2017-09-01

Several probiotics were effective in the eradication treatment for Helicobacter pylori (Hp), but their comparative efficacy was unknown. To compare the efficacy of different probiotics when supplemented in Hp eradication therapy. A comprehensive search was conducted to identify all relevant studies in multiple databases and previous meta-analyses. Bayesian network meta-analysis was performed to combine direct and indirect evidence and estimate the relative effects. One hundred and forty studies (44 English and 96 Chinese) were identified with a total of 20,215 patients, and more than 10 probiotic strategies were supplemented in Hp eradication therapy. The rates of eradication and adverse events were 84.1 and 14.4% in probiotic group, while 70.5 and 30.1% in the control group. In general, supplementary probiotics were effective in improving the efficacy of Hp eradication and decreasing the incidence of adverse events, despite of few ineffective subtypes. In triple eradication therapy, there was no significant difference among the effective probiotics, and combined probiotics did not show a better efficacy and tolerance than single use. In triple therapy of 7 days and 14 days, Lactobacillus acidopilus was a slightly better choice, while Saccharomyces boulardii was more applicable for 10-day triple therapy. Compared to placebo, most probiotic strategies were effective when supplemented in Hp eradication therapy. In triple eradication therapy, no probiotic showed a superior efficacy to the others. Compared to single use, combined probiotics could not improve the efficacy or tolerance significantly. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Combined BTK and PI3Kδ Inhibition with Acalabrutinib and ACP-319 Improves Survival and Tumor Control in CLL Mouse Model.

PubMed

Niemann, Carsten U; Mora-Jensen, Helena I; Dadashian, Eman L; Krantz, Fanny; Covey, Todd; Chen, Shih-Shih; Chiorazzi, Nicholas; Izumi, Raquel; Ulrich, Roger; Lannutti, Brian J; Wiestner, Adrian; Herman, Sarah E M

2017-10-01

Purpose: Targeting the B-cell receptor (BCR) pathway with inhibitors of Bruton tyrosine kinase (BTK) and PI3Kδ is highly effective for the treatment of chronic lymphocytic leukemia (CLL). However, deep remissions are uncommon, and drug resistance with single-agent therapy can occur. In vitro studies support the effectiveness of combing PI3Kδ and BTK inhibitors. Experimental Design: As CLL proliferation and survival depends on the microenvironment, we used murine models to assess the efficacy of the BTK inhibitor acalabrutinib combined with the PI3Kδ inhibitor ACP-319 in vivo We compared single-agent with combination therapy in TCL1-192 cell-injected mice, a model of aggressive CLL. Results: We found significantly larger reductions in tumor burden in the peripheral blood and spleen of combination-treated mice. Although single-agent therapy improved survival compared with control mice by a few days, combination therapy extended survival by over 2 weeks compared with either single agent. The combination reduced tumor proliferation, NF-κB signaling, and expression of BCL-xL and MCL-1 more potently than single-agent therapy. Conclusions: The combination of acalabrutinib and ACP-319 was superior to single-agent treatment in a murine CLL model, warranting further investigation of this combination in clinical studies. Clin Cancer Res; 23(19); 5814-23. ©2017 AACR . ©2017 American Association for Cancer Research.

[Therapeutic effects of the integrated acupuncture and Chinese herbal medicine on reflux esophagitis].

PubMed

Zhang, Wan; Li, Bolin; Sun, Jianhui; Wang, Zhikun; Zhang, Nana; Shi, Fang; Pei, Lin

2017-07-12

To compare the differences in the clinical therapeutic effects on reflux esophagitis among the combined therapy of huazhuo jiedu jiangni decoction (the decoction for resolving the turbid, detoxification and reducing the pathologic upward qi in short) and acupuncture, omeprazole and Chinese herbal medicine. Ninety patients were randomized into 3 groups, 4 cases of them were dropped off. Finally, there were 29 cases in the combined therapy group with acupuncture and the decoction, 29 cases in the western medication group and 28 cases in the Chinese herbal medicine group in the statistical analysis. In the combined therapy group with acupuncture and the decoction, the decoction was prescribed recurrence rate. The therapeutic effects are better than the simple application of either Chinese herbal medicine or omeprazole. for oral administration. Additionally, acupuncture was applied to Neiguan (PC 6), Zusanli (ST 36), Zhongwan (CV 12), Ganshu (BL 18), Danshu (BL 19) and Taichong (LR 3). The decoction was applied one dose a day and acupuncture was once a day. In the western medication group, omeprazole capsules, 20 mg were prescribed for oral administration, twice a day. In the Chinese herbal medicine group, the decoction was simply applied. The treatment was 8 weeks in the 3 groups and the follow-up visit was 6 months. The score of reflux disorder questionnaire (RDQ) and the changes in esophageal mucosa under gastroscope were observed before and after treatment; the clinical therapeutic effects and recurrence rate were evaluated in the 3 groups. In 4 and 8 weeks of treatment, RDQ scores in the 3 groups were all reduced as compared with those before treatment (all P <0.05). In 4 weeks of treatment, RDQ score in the combined therapy group with acupuncture and Chinese herbal medicine was lower than that in the western medication group ( P <0.05). In 8 weeks of treatment, RDQ score in the combined therapy group with acupuncture and Chinese herbal medicine was lower than those in the western medication group and the Chinese herbal medicine group (both P <0.05). In follow-up visit for 6 months, the recurrence rate in the combined therapy group with acupuncture and the decoction was lower than those in the other two groups (both P <0.05). In 8 weeks of treatment, the total effective rate for clinical symptoms and that observed under gastroscope in the combined therapy group with acupuncture and the decoction were all better than those in the western medication group and the Chinese herbal medicine group (all P <0.05). The combined therapy of huazhuo jiedu jiangni decoction and acupuncture achieve the definite therapeutic effects on reflux esophagitis, relieve the symptoms, protect gastric mucosa and reduce the.

Cost-effectiveness of combined oral bisphosphonate therapy and falls prevention exercise for fracture prevention in the USA.

PubMed

Mori, T; Crandall, C J; Ganz, D A

2017-02-01

We developed a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women without prior major osteoporotic fractures over a lifetime horizon. At ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a conventionally accepted threshold compared with bisphosphonates alone. The purpose of this study was to examine the cost-effectiveness of the combined strategy of oral bisphosphonate therapy for 5 years and falls prevention exercise for 1 year compared with either strategy in isolation. We calculated incremental cost-effectiveness ratios [ICERs] (2014 US dollars per quality-adjusted life year [QALY]), using a Markov microsimulation model among hypothetical cohorts of community-dwelling US white women with different starting ages (65, 70, 75, and 80) without prior history of hip, vertebral, or wrist fractures over a lifetime horizon from the societal perspective. At ages 65, 70, 75, and 80, the combined strategy had ICERs of $202,020, $118,460, $46,870, and $17,640 per QALY, respectively, compared with oral bisphosphonate therapy alone. The combined strategy provided better health at lower cost than falls prevention exercise alone at ages 70, 75, and 80. In deterministic sensitivity analyses, results were particularly sensitive to the change in the opportunity cost of participants' time spent exercising. In probabilistic sensitivity analyses, the probabilities of the combined strategy being cost-effective compared with the next best alternative increased with age, ranging from 35 % at age 65 to 48 % at age 80 at a willingness-to-pay of $100,000 per QALY. Among community-dwelling US white women ages 75 and 80, adding 1 year of exercise to 5 years of oral bisphosphonate therapy is cost-effective at a willingness-to-pay of $100,000 per QALY, compared with oral bisphosphonate therapy only. This analysis will help clinicians and policymakers make better decisions about treatment options to reduce fracture risk.

Treatment adherence and real-life effectiveness of topical therapy in patients with mild or moderate psoriasis: uptake of scientific evidence in clinical practice and dermatologists' preferences for alternative treatment options.

PubMed

Neri, L; Miracapillo, A

2015-02-01

Topical corticosteroids and the vitamin D analogue calcipotriol are the cornerstone of therapy for patients with mild-to-moderate plaque psoriasis. Lack of patients' adherence leads to suboptimal effectiveness of topical therapy in real-life practice. The fixed combination betamethasone/calcipotriol gel is more effective and safe than the administration of single components and may enhance patients' adherence. We aimed at evaluating the pattern of care and dermatologists' expert opinion toward the available topical treatments for the management of mild-to-moderate psoriasis in Italy. We enrolled 242 Italian dermatologists and collected information related to their practice pattern and opinion toward available topical treatments with a face-to-face structured interview. We evaluated dermatologists' ratings of therapy with 16 items tapping their opinion toward the relevance and satisfaction toward 8 therapy attributes in clinical practices which tapped aspects of real-life effectiveness, adherence promotion, toxicity, convenience of use. Ratings occurred along a 10-point scale. We compared single-attribute and weighted overall therapy ratings across alternative treatment options with random-intercept linear models to account for ratings clustering within dermatologists. There was a wide variation in practice patterns: 1/3 of dermatologist had seen more than 30 patients with psoriasis while around 1/4 had seen less than 10 patients. The fixed combination betamethasone/calcipotriol gel was considered superior to monotherapies in all the eight attributes considered which tapped aspects of real-life effectiveness, adherence promotion, toxicity, convenience of use. Participant dermatologists' strongly preferred the fixed betamethasone/calcipotriol combination gel over both the fixed combination ointment formulation and corticosteroid or vitamin D analogues monotherapies. Such findings are in line with evidence from randomized controlled trials and few observational studies demonstrating superior clinical outcomes, quality of life, tolerability and lower risk of side effect in patients treated with the fixed combination of betamethasone/calcipotriol gel.

Combined treatment modalities for age related macular degeneration.

PubMed

Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

2011-02-01

Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

Combination therapies for neurobehavioral and cognitive recovery after experimental traumatic brain injury: is more better?

PubMed Central

Kline, Anthony E.; Leary, Jacob B.; Radabaugh, Hannah L.; Cheng, Jeffrey P.; Bondi, Corina O.

2016-01-01

Traumatic brain injury (TBI) is a significant health care crisis that affects two million individuals in the United Sates alone and over ten million worldwide each year. While numerous monotherapies have been evaluated and shown to be beneficial at the bench, similar results have not translated to the clinic. One reason for the lack of successful translation may be due to the fact that TBI is a heterogeneous disease that affects multiple mechanisms, thus requiring a therapeutic approach that can act on complementary, rather than single, targets. Hence, the use of combination therapies (i.e., polytherapy) has emerged as a viable approach. Stringent criteria, such as verification of each individual treatment plus the combination, a focus on behavioral outcome, and post-injury vs. pre-injury treatments, were employed to determine which studies were appropriate for review. The selection process resulted in 37 papers that fit the specifications. The review, which is the first to comprehensively assess the effects of combination therapies on behavioral outcomes after TBI, encompasses five broad categories (inflammation, oxidative stress, neurotransmitter dysregulation, neurotrophins, and stem cells, with and without rehabilitative therapies). Overall, the findings suggest that combination therapies can be more beneficial than monotherapies as indicated by 46% of the studies exhibiting an additive or synergistic positive effect versus on 19% reporting a negative interaction. These encouraging findings serve as an impetus for continued combination studies after TBI and ultimately for the development of successful clinically relevant therapies. PMID:27166858

Clinical effectiveness of rivastigmine monotherapy and combination therapy in Alzheimer's patients.

PubMed

Sonali, Nirmal; Tripathi, Manjari; Sagar, Rajesh; Velpandian, Thirumurthy; Subbiah, Vivekanandhan

2013-02-01

Rivastigmine is an acetylcholinesterase inhibitor; the genotype data seen alongside the phenotype data explain the mutation or the molecular genetics involved and also help to relate the phenotype of an individual with their genotype. To determine the clinical effectiveness of CYP2D6, CYP3A4, CYP2C9/19, and UGT polymorphism on the steady-state plasma concentrations and therapeutic outcome of rivastigmine monotherapy and combination therapy in patients with Alzheimer's disease. In this study, a significant allele frequency was observed for CYP2D6*3 polymorphism in patients under rivastigmine combination therapy (A>del = 0.50 [patients] and A>del = 0.20 [controls]), UGT2B7 (T = 0.17 [patients] and 0.33 [Controls], and UGT1A9*5 A = 0.58 [patients] and 0.26 [Controls]). The drug levels and P value of responders/nonresponders were found to be 0.17 ± 0.08/0.22 ± 0.16 and 0.574 for rivastigmine and 0.18 ± 0.11/0.66 ± 0.63 and 0.009 for rivastigmine in combination therapy and 1.40 ± 0.65/0.59 ± 0.84 and 0.05 for memantine in combination therapy. Poor metabolizer subjects of UGT2B7 polymorphism in patients under rivastigmine combination therapy have higher drug levels with a poor response to the drug treatments. © 2012 Blackwell Publishing Ltd.

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel.

PubMed

Wein, Alexander N; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T; Leppla, Stephen H

2013-02-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wildtype lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an antimitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an antiangiogenesis therapy such as sunitinib or sorafinib.

Combined treatment in punctate inner choroidopathy

PubMed Central

Terelak-Borys, Barbara; Zagajewska, Katarzyna; Jankowska-Lech, Irmina; Tesla, Piotr; Grabska-Liberek, Iwona

2016-01-01

Purpose The purpose of this study was to describe a combination treatment for choroidal neovascular (CNV) membrane, secondary to punctate inner choroidopathy (PIC). Patient and methods A 44-year-old female patient was diagnosed with PIC complicated by the development of recurrent juxtafoveal neovascular membrane. The treatment included a sequence of monotherapy regimens: systemic steroid therapy, photodynamic therapy, and intravitreal injections of vascular endothelial growth factor (VEGF) inhibitor (anti-VEGF). Owing to the CNV membrane resistance to various types of monotherapy, a combination treatment consisting of local injections of steroid underneath the Tenon’s capsule and intravitreal anti-VEGF injections was used. Results Systemic steroid therapy resulted in rapid local improvement with a very short remission period. No positive effects of photodynamic therapy were observed. Sequential anti-VEGF injections led to remission periods of several months. Permanent regression of CNV membrane was achieved following combined local application of steroid and intravitreal anti-VEGF injections. Conclusion A combination treatment including steroid and anti-VEGF medication characterized by anti-inflammatory and antiangiogenic effects may be a very beneficial option for the treatment of recurrent CNV membrane as a complication of PIC. PMID:27729795

Several methods and apparatus of low-energy laser therapy in veterinary practice

NASA Astrophysics Data System (ADS)

Svirin, Vaytcheslav N.; Rogatkin, Dmitrii A.; Barybin, Vitalii F.

1998-12-01

During same years various medical effect of low-energy laser therapy in veterinary were tested. We established that the laser low-energy therapy can be very effective for treatment such animal's diseases as mastitis and demodekose when certain combinations of laser beam parameters are used. This combinations were taken as the principle of a number of laser veterinary apparatus, which we started to produce at `POLUS'. It is our series of apparatus `VEGA-MB' and `VETLAS-3', which is real used today for dogs and cows treatment in Russia.

Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.

PubMed

Cox, Georgina R; Callahan, Patch; Churchill, Rachel; Hunot, Vivien; Merry, Sally N; Parker, Alexandra G; Hetrick, Sarah E

2014-11-30

Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 June 2014. The register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when outcomes were measured on different scales. We included eleven studies, involving 1307 participants in this review. We also identified one ongoing study, and two additional ongoing studies that may be eligible for inclusion. Studies recruited participants with different severities of disorder and with a variety of comorbid disorders, including anxiety and substance use disorder, therefore limiting the comparability of the results. Regarding the risk of bias in studies, just under half the studies had adequate allocation concealment (there was insufficient information to determine allocation concealment in the remainder), outcome assessors were blind to the participants' intervention in six studies, and in general, studies reported on incomplete data analysis methods, mainly using intention-to-treat (ITT) analyses. For the majority of outcomes there were no statistically significant differences between the interventions compared. There was limited evidence (based on two studies involving 220 participants) that antidepressant medication was more effective than psychotherapy on measures of clinician defined remission immediately post-intervention (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the medication group and 53.7% in the psychotherapy group rated as being in remission. There was limited evidence (based on three studies involving 378 participants) that combination therapy was more effective than antidepressant medication alone in achieving higher remission from a depressive episode immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of participants treated with combination therapy and 57.8% of participants treated with medication, rated as being in remission. There was no evidence to suggest that combination therapy was more effective than psychological therapy alone, based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI 0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in various ways across studies and could not be combined in meta-analyses. However, some trials measured suicidal ideation using standardised assessment tools suitable for meta-analysis. In one study involving 188 participants, rates of suicidal ideation were significantly higher in the antidepressant medication group (18.6%) compared with the psychological therapy group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at six to nine months (OR 0.26, 95% CI 0.07 to 0.98), with 13.6% of participants in the medication group and 3.9% of participants in the psychological therapy group reporting suicidal ideation. It was unclear what the effect of combination therapy was compared with either antidepressant medication alone or psychological therapy alone on rates of suicidal ideation. The impact of any of the assigned treatment packages on drop out was also mostly unclear across the various comparisons in the review.Limited data and conflicting results based on other outcome measures make it difficult to draw conclusions regarding the effectiveness of any specific intervention based on these outcomes. There is very limited evidence upon which to base conclusions about the relative effectiveness of psychological interventions, antidepressant medication and a combination of these interventions. On the basis of the available evidence, the effectiveness of these interventions for treating depressive disorders in children and adolescents cannot be established. Further appropriately powered RCTs are required.

Safety and Efficacy of Combined Chelation Therapy with Deferasirox and Deferoxamine in a Gerbil Model of Iron Overload

PubMed Central

Otto-Duessel, Maya; Brewer, Casey; Gonzalez, Ignacio; Nick, Hanspeter; Wood, John C.

2010-01-01

Introduction Combined therapy with deferoxamine (DFO) and deferasirox (DFX) may be performed empirically when DFX monotherapy fails. Given the lack of published data on this therapy, the study goal was to assess the safety and efficacy of combined DFO/DFX therapy in a gerbil model. Methods Thirty-two female Mongolian gerbils 8–10 weeks old were divided into 4 groups (sham chelated, DFO, DFX, DFO/DFX). Each received 10 weekly injections of 200 mg/kg iron dextran prior to initiation of 12 weeks of chelation. Experimental endpoints were heart and liver weights, iron concentration and histology. Results In the heart, there was no significant difference among the treatment groups for wet-to-dry ratio, iron concentration and iron content. DFX-treated animals exhibited lower organ weights relative to sham-chelated animals (less iron-mediated hypertrophy). DFO-treated organs did not differ from sham-chelated organs in any aspects. DFX significantly cleared hepatic iron. No additive effects were observed in the organs of DFO/DFX-treated animals. Conclusions Combined DFO/DFX therapy produced no detectable additive effect above DFX monotherapy in either the liver or heart, suggesting competition with spontaneous iron elimination mechanisms for chelatable iron. Combined therapy was well tolerated, but its efficacy could not be proven due to limitations in the animal model. PMID:19018129

Safety of coadministration of ezetimibe and statins in patients with hypercholesterolaemia: a meta-analysis.

PubMed

Luo, L; Yuan, X; Huang, W; Ren, F; Zhu, H; Zheng, Y; Tang, L

2015-05-01

Hypercholesterolaemia is a pivotal risk factor for cardiovascular and cerebrovascular disease and is treated with many effective lipid-lowering agents. Statins are often used alone or in combination with ezetimibe. Combination therapy is more effective because of its complementary approach, which has major benefits for patients with unmanageable lipid levels. Extensive application of combination therapy has resulted in an increased incidence of side-effects, which has raised our concern. To evaluate the evidence associated with the safety of coadministration of ezetimibe with statins. Three electronic databases were searched (PubMed, EMBASE and Cochrane Library) from January 2002 to October 2014. Two independent reviewers critically identify randomised controlled trials (RCT), extracted the data and assessed trial quality. A total ot 20 RCT met inclusion criteria, including 14,856 patients. A fixed-effects model was used for meta-analysis to assess the safety of combination therapy. Coadministration of ezetimibe and statins did not result in significant increases in total adverse events (30% vs 29%, P = 0.34), serious adverse events (2% vs 1.6%, P = 0.81), treatment discontinuations (3.5% vs 2.9%, P = 0.22), gastrointestinal adverse events (5% vs 4%, P = 0.08), allergic reactions or rashes (0.9% vs 1.3%, P = 0.33), creatine kinase > 10 × upper limit of normal (ULN) (0.2% vs 0.2%, P = 0.86), alanine aminotransferase > 3 × ULN (0.5% vs 0.4%, P = 0.96) and aspartate aminotransferase > 3 × ULN (0.4% vs 0.4%, P = 0.58). The incidence of adverse events was similar between ezetimibe-statin combination therapy and statin monotherapy; thus, we recommend combination therapy for patients with hypercholesterolaemia at high risk for cardiovascular and cerebrovascular disease. © 2015 Royal Australasian College of Physicians.

Combined Treatment Effects of Radiation and Immunotherapy: Studies in an Autochthonous Prostate Cancer Model

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

Wada, Satoshi; Harris, Timothy J.; Tryggestad, Erik

2013-11-15

Purpose: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. Methods and Materials: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors. Results: The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evidentmore » with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes. Conclusions: Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.« less

A comparison of latanoprost monotherapy with a combination therapy of timolol/dorzolamide in patients with primary open-angle glaucoma.

PubMed

Caça, Ihsan; Simsek, Hüseyin; Unlü, Kaan; Ari, Seyhmus; Keklikçi, Ugur

2006-01-01

We compared latanoprost monotherapy therapy with timolol/ dorzolamide in patients with primary open-angle glaucoma to evaluate the effects on intraocular pressure (IOP) and occurrence of adverse events. IOP and topical side effects were evaluated at the beginning, first, and third months. Mean IOP was decreased at the third month. The most common side effect was hyperemia (43.6%). We concluded that latanoprost reduces IOP better than fixed combination and its topical side effects are tolerable.

[Treatment with the use of microcurrent lymphatic drainage physiotherapy during the postoperative period following rhinoplastic surgery].

PubMed

Aleksanyan, T A; Kazantsev, E V

The objective of the present study was to evaluate the effectiveness of the combined treatment of the patients who had undergone either primary or secondary rhinoplastic surgery with the use of photo- and magnetic therapy in comparison with the effectiveness of phototherapy in the combination with microcurrent therapy. The patients were divided into four groups depending on the type of the surgical intervention and the mode of the combined physiotherapeutic treatment. All the patients were given combined physiotherapeutic treatment in addition to the standard pharmacotherapy starting from the second day of the postoperative period. The patients of groups 1 and 3 received phototherapy in the combination with magnetic therapy while those in groups 2 and 4 were treated by phototherapy in the combination with microcurrent lymphatic drainage physiotherapy. It was shown that the different combinations of physiotherapeutic modalities during the postoperative period following primary «closed» rhinoplasty were not different significantly in terms of effectiveness. After secondary «closed» rhinoplasty, the combination of phototherapy with the application of microcurrents looks more preferable. It is concluded that microcurrent lymphdraining physiotherapy should be regarded as the priority component of the combined physiotherapeutic treatment during the postoperative period following secondary «closed» rhinoplasty.

Does Preference for Type of Treatment Matter? A Study of Exposure In Vivo With or Without Hypnosis in the Treatment of Panic Disorder With Agoraphobia.

ERIC Educational Resources Information Center

Dyck, Richard Van; Spinhoven, Philip

1997-01-01

Explores whether a client's preference for a certain therapy effects treatment efficacy. Treatment of 64 agoraphobic patients with either exposure in vivo or exposure combined with hypnosis show that, although patients' preference clearly shifted in favor of a combined therapy approach, no effect of preference on outcome was evident. (RJM)

[The use of mood stabilizers in preventive treatment of patients with schizoaffective disorders].

PubMed

Chritinin, D F; Sumarokova, M A

2014-01-01

To study an effect of combination therapy consisting of mood stabilizers on the quality of remission in patients with schizoaffective disorders. Authors examined 56 outpatients with ICD-10 diagnosis of schizoaffective disorder (F25). Patients in remission received anti-relapse therapy with antipsychotics and were not treated with mood stabilizers for at least two years, and then they received a combined anti-relapse therapy, including both antipsychotics and mood stabilizers. The combined use of pharmacotherapy creates a better remission. No statistically significant differences in the effect of different groups of mood stabilizers on the average duration of remission are identified. The inclusion of mood stabilizers in the scheme of preventive treatment has no effect on the average duration of subsequent hospitalization. Mood stabilizers are effective in the prevention of suicidal behavior in patients with schizoaffective disorder, they reduce the risk of disability in patients with schizoaffective disorder and increase compliance.

Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.

PubMed

Quinn, T J; Healy, N; Sara, A; Maggi, E; Claros, C S; Kabarriti, R; Scandiuzzi, L; Liu, L; Gorecka, J; Adem, A; Basu, I; Yuan, Z; Guha, C

2017-01-01

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.

Ezetimibe-Statin Combination Therapy.

PubMed

Nußbaumer, Barbara; Glechner, Anna; Kaminski-Hartenthaler, Angela; Mahlknecht, Peter; Gartlehner, Gerald

2016-07-01

To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus. This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry. Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]). In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

A phase III, open-label, multicenter study to evaluate the safety and efficacy of long-term triple combination therapy with azilsartan, amlodipine, and hydrochlorothiazide in patients with essential hypertension.

PubMed

Rakugi, Hiromi; Shimizu, Kohei; Nishiyama, Yuya; Sano, Yuhei; Umeda, Yuusuke

2018-06-01

Patients with essential hypertension who are receiving treatment with an angiotensin II receptor blocker and a calcium channel blocker often develop inadequate blood pressure (BP) control and require the addition of a diuretic. This study aimed to evaluate the long-term safety and efficacy of a triple combination therapy with 20 mg azilsartan (AZL), 5 mg amlodipine (AML) and 12.5 mg hydrochlorothiazide (HCTZ). The phase III, open-label, multicenter study (NCT02277691) comprised a 4-week run-in period and 52-week treatment period. Patients with inadequate BP control despite AZL/AML therapy (n = 341) received 4 weeks' treatment with AZL/AML (combination tablet) + HCTZ (tablet) and 4 weeks' treatment with AZL/AML/HCTZ (combination tablet) in a crossover manner, followed by AZL/AML/HCTZ (combination tablet) from Week 8 of the treatment period up to Week 52. The primary and secondary endpoints were long-term safety and BP (office and home), respectively. Most adverse events (AEs) were mild or moderate in intensity, and no deaths or treatment-related serious AEs were reported. The triple therapy provided consistent BP-lowering effects in both office and home measurements. The triple combination therapy with AZL/AML/HCTZ was well tolerated and effective for 52 weeks in Japanese patients with essential hypertension.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Rees, Karen; Casas, Juan P; Huffman, Mark

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To determine the effectiveness of fixed-dose combination therapy on optimising CVD risk factors and reducing CVD fatal and non-fatal events for both primary and secondary prevention of CVD. Details of CVD events and risk factors included are listed in the methods. We will also determine any adverse events associated with taking fixed-dose combination therapy. This will include studies conducted in both developed and developing regions of the world. PMID:25267903

Sinoporphyrin sodium triggered sono-photodynamic effects on breast cancer both in vitro and in vivo.

PubMed

Liu, Yichen; Wang, Pan; Liu, Quanhong; Wang, Xiaobing

2016-07-01

Sono-photodynamic therapy (SPDT) is a promising anti-cancer strategy. Briefly, SPDT combines ultrasound and light to activate sensitizers that produce mechanical, sonochemical and photochemical activities. Sinoporphyrin sodium (DVDMS) is a newly identified sensitizer that shows great potential in both sonodynamic therapy (SDT) and photodynamic therapy (PDT). In this study, we primarily evaluated the combined effects of SDT and PDT by using DVDMS on breast cancer both in vitro and in vivo. In vitro, DVDMS-SPDT elicits much serious cytotoxicity compared with either SDT or PDT alone by MTT and colony formation assays. 2',7'-Dichlorodihydrofluo-rescein-diacetate (DCFH-DA) and dihydroethidium (DHE) staining revealed that intracellular reactive oxygen species (ROS) were significantly increased in groups given combined therapy. Terephthalic acid (TA) method and FD500-uptake assay reflected that cavitational effects and cell membrane permeability changes after ultrasound irradiation were also involved in the enhancement of combination therapy. In vivo, DVDMS-SPDT markedly inhibits the tumor volume and tumor weight growth. Hematoxylin-eosin staining and immunohistochemistry analysis show DVDMS-SPDT greatly suppressed tumor proliferation. Further, DVDMS-SPDT significantly inhibits tumor lung metastasis in the highly metastatic 4T1 mouse xenograft model, which is consistent well with the in vitro findings evaluated by transwell assay. Moreover, DVDMS-SPDT did not produces obvious effect on body weight and major organs in 4T1 xenograft model. The results suggest that by combination SDT and PDT, the sensitizer DVDMS would produce much better therapeutic effects, and DVDMS-SPDT may be a potential strategy against highly metastatic breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

EGFR Targeted Therapies and Radiation: Optimizing Efficacy by Appropriate Drug Scheduling and Patient Selection

PubMed Central

Cuneo, Kyle C.; Nyati, Mukesh K.; Ray, Dipankar; Lawrence, Theodore S.

2015-01-01

The epidermal growth factor receptor (EGFR) plays an important role in tumor progression and treatment resistance for many types of malignancies including head and neck, colorectal, and nonsmall cell lung cancer. Several EGFR targeted therapies are efficacious as single agents or in combination with chemotherapy. Given the toxicity associated with chemoradiation and poor outcomes seen in several types of cancers, combinations of EGFR targeted agents with or without chemotherapy have been tested in patients receiving radiation. To date, the only FDA approved use of an anti-EGFR therapy in combination with radiation therapy is for locally advanced head and neck cancer. Given the important role EGFR plays in lung and colorectal cancer and the benefit of EGFR inhibition combined with chemotherapy in these disease sites, it is perplexing why EGFR targeted therapies in combination with radiation or chemoradiation have not been more successful. In this review we summarize the clinical findings of EGFR targeted therapies combined with radiation and chemoradiation regimens. We then discuss the interaction between EGFR and radiation including radiation induced EGFR signaling, the effect of EGFR on DNA damage repair, and potential mechanisms of radiosensitization. Finally, we examine the potential pitfalls with scheduling EGFR targeted therapies with chemoradiation and the use of predictive biomarkers to improve patient selection. PMID:26205191

Synergistic Increase of Serum BDNF in Alzheimer Patients Treated with Cerebrolysin and Donepezil: Association with Cognitive Improvement in ApoE4 Cases

PubMed Central

Alvarez, Irene; Iglesias, Olalla; Crespo, Ignacio; Figueroa, Jesus; Aleixandre, Manuel; Linares, Carlos; Granizo, Elias; Garcia-Fantini, Manuel; Marey, Jose; Masliah, Eliezer; Winter, Stefan; Muresanu, Dafin; Moessler, Herbert

2016-01-01

Background: Low circulating brain derived neurotrophic factor may promote cognitive deterioration, but the effects of neurotrophic and combination drug therapies on serum brain derived neurotrophic factor were not previously investigated in Alzheimer’s disease. Methods: We evaluated the effects of Cerebrolysin, donepezil, and the combined therapy on brain derived neurotrophic factor serum levels at week 16 (end of Cerebrolysin treatment) and week 28 (endpoint) in mild-to-moderate Alzheimer’s disease patients. Results: Cerebrolysin, but not donepezil, increased serum brain derived neurotrophic factor at week 16, while the combination therapy enhanced it at both week 16 and study endpoint. Brain derived neurotrophic factor responses were significantly higher in the combination therapy group than in donepezil and Cerebrolysin groups at week 16 and week 28, respectively. Brain derived neurotrophic factor increases were greater in apolipoprotein E epsilon-4 allele carriers, and higher brain derived neurotrophic factor levels were associated with better cognitive improvements in apolipoprotein E epsilon-4 allele patients treated with Cerebrolysin and the combined therapy. Conclusion: Our results indicate a synergistic action of Cerebrolysin and donepezil to increase serum brain derived neurotrophic factor and delaying cognitive decline, particularly in Alzheimer’s disease cases with apolipoprotein E epsilon-4 allele. PMID:27207906

The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review

PubMed Central

Fekrazad, Reza; Naghdi, Nafiseh; Nokhbatolfoghahaei, Hanieh; Bagheri, Hossein

2016-01-01

Several methods have been employed for cancer treatment including surgery, chemotherapy and radiation therapy. Today, recent advances in medical science and development of new technologies, have led to the introduction of new methods such as hormone therapy, Photodynamic therapy (PDT), treatments using nanoparticles and eventually combinations of lasers and nanoparticles. The unique features of LASERs such as photo-thermal properties and the particular characteristics of nanoparticles, given their extremely small size, may provide an interesting combined therapeutic effect. The purpose of this study was to review the simultaneous application of lasers and metal nanoparticles for the treatment of cancers with epithelial origin. A comprehensive search in electronic sources including PubMed, Google Scholar and Science Direct was carried out between 2000 and 2013. Among the initial 400 articles, 250 articles applied nanoparticles and lasers in combination, in which more than 50 articles covered the treatment of cancer with epithelial origin. In the future, the combination of laser and nanoparticles may be used as a new or an alternative method for cancer therapy or diagnosis. Obviously, to exclude the effect of laser’s wavelength and nanoparticle’s properties more animal studies and clinical trials are required as a lack of perfect studies PMID:27330701

Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy.

PubMed

Yu, Shui; Li, Hengjin

2016-01-01

The current study aimed to assess the value of microplasma radiofrequency technology combined with triamcinolone for the therapy of Chinese patients with hypertrophic scar. A total of 120 participants with hypertrophic scars were enrolled in the current study. Participants were divided into two groups based on sex, and then randomly and evenly divided into four groups (Groups A, B, C, and D). Participants in Group A received microplasma radiofrequency technology combined with triamcinolone. Participants in Group B received microplasma radiofrequency technology combined with normal saline. Participants in Groups C and D received triamcinolone (40 and 10 mg/mL) injected directly into scar. Experienced physicians evaluated the condition of scars according to the Vancouver Scar Scale 1 month before and after the therapy. There was no difference in age, sex, area, height and location of scars, and Vancouver Scar Scale scores before the therapy between any groups (P>0.05 for all). Vancouver Scar Scale scores after the therapy were significantly lower than those before the therapy in all groups (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group A were significantly lower than those after the therapy in Groups B and C (P<0.05 for all). Vancouver Scar Scale scores after the therapy in Group B were significantly higher than those after the therapy in Group C (P<0.05 for all) and similar to those after the therapy in Group D (P>0.05 for all). Incidences of tissue atrophy after the therapy were significantly lower in Groups A and B than in Group C (P<0.05 for all) and similar among Groups A, B, and D (P>0.05 for all). Microplasma radiofrequency technology combined with triamcinolone improved the therapeutic effect on Chinese patients with hypertrophic scar and reduced the risk of tissue atrophy compared with the use of either microplasma radiofrequency technology or triamcinolone injection alone.

Automicroneedle therapy system combined with topical tretinoin shows better regenerative effects compared with each individual treatment.

PubMed

Kim, J H; Park, H Y; Jung, M; Choi, E H

2013-01-01

Regenerative therapy is a relatively new dermatological field. However, the currently available topical agents are unsuitable for transdermal drug delivery because of their high molecular weight and low liposolubility. Therefore, a more effective transdermal drug delivery system is needed in order to achieve better therapeutic effects with these agents. A recently introduced microneedle therapy system (MTS), which is a mechanical method for making minute holes in the skin, improves transdermal delivery. A recently developed refinement of this technique, the automicroneedle therapy system (AMTS), has several advantages over the traditional MTS, as it can achieve consistent results because of its automatic punching method. To evaluate the cutaneous effects of an AMTS in combination with topical tretinoin. Twelve hairless mice were divided into two groups, and the dorsal skin of each mouse was marked down the centre. The first group was treated with the AMTS plus 0.025% tretinoin on one side of the back, and with 0.025% tretinoin only on the other side. The other group was treated with the AMTS and vehicle on one side, while the other side was left untreated. The effects on cutaneous regeneration and the treatment side-effects were evaluated by functional assessment including transepidermal water loss and skin hydration, and by histopathology including epidermal and dermal thickness, and density of collagen fibres. Western blotting and real-time reverse transcriptase PCR were also performed to determine protein and mRNA expression of procollagen type 1 and matrix metalloproteinase-13. Compared with the individual treatments (the AMTS alone or tretinoin alone) the combination of tretinoin plus the AMTS produced greater dermal regeneration as a result of increased proliferation of collagen fibres. This combination therapy did not result in treatment-related adverse effects. An AMTS combined with topical tretinoin is a safe and effective method for skin regeneration, which works by increasing collagen production, and might be a new therapeutic option for regenerative therapy. © The Author(s). CED © 2012 British Association of Dermatologists.

Whole Body Microwave Irradiation for Improved Dacarbazine Therapeutical Action in Cutaneous Melanoma Mouse Model

PubMed Central

Albulescu, Lucian; Iacob, Nicusor; Ighigeanu, Daniel

2013-01-01

A cutaneous melanoma mouse model was used to test the efficacy of a new therapeutical approach that uses low doses of cytostatics in conjunction with mild whole body microwave exposure of 2.45 GHz in order to enhance cytostatics antitumoral effect. Materials and Methods. A microwave exposure system for C57BL/6 mouse whole body microwave irradiation was designed; groups of 40 mice (males and females) bearing experimental tumours were subjected to a combined therapy comprising low doses of dacarbazine in combination with mild whole body irradiation. Clinical parameters and serum cytokine testing using xMAP technology were performed. Results. The group that was subjected to combined therapy, microwave and cytostatic, had the best clinical evolution in terms of overall survival, tumour volume, and metastatic potential. At day 14 the untreated group had 100% mortality, while in the combined therapy group 40% of mice were surviving. Quantifying serum IL-1β, IL-6, IL-10, IL-12 (p70), IFN-γ, GM-CSF, TNF-α, MIP-1α, MCP-1, and KC during tumorigenesis and therapy found that the combined experimental therapy decreases all the inflammatory cytokines, except chemokine MCP-1 that was found increased, suggesting an increase of the anti-tumoral immune response triggered by the combined therapy. The overall metastatic process is decreased in the combined therapy group. PMID:24377047

Whole body microwave irradiation for improved dacarbazine therapeutical action in cutaneous melanoma mouse model.

PubMed

Neagu, Monica; Constantin, Carolina; Martin, Diana; Albulescu, Lucian; Iacob, Nicusor; Ighigeanu, Daniel

2013-01-01

A cutaneous melanoma mouse model was used to test the efficacy of a new therapeutical approach that uses low doses of cytostatics in conjunction with mild whole body microwave exposure of 2.45 GHz in order to enhance cytostatics antitumoral effect. Materials and Methods. A microwave exposure system for C57BL/6 mouse whole body microwave irradiation was designed; groups of 40 mice (males and females) bearing experimental tumours were subjected to a combined therapy comprising low doses of dacarbazine in combination with mild whole body irradiation. Clinical parameters and serum cytokine testing using xMAP technology were performed. Results. The group that was subjected to combined therapy, microwave and cytostatic, had the best clinical evolution in terms of overall survival, tumour volume, and metastatic potential. At day 14 the untreated group had 100% mortality, while in the combined therapy group 40% of mice were surviving. Quantifying serum IL-1 β , IL-6, IL-10, IL-12 (p70), IFN- γ , GM-CSF, TNF- α , MIP-1 α , MCP-1, and KC during tumorigenesis and therapy found that the combined experimental therapy decreases all the inflammatory cytokines, except chemokine MCP-1 that was found increased, suggesting an increase of the anti-tumoral immune response triggered by the combined therapy. The overall metastatic process is decreased in the combined therapy group.

[Clinical Efficacy of Alternate-Day S-1/Letrozole Combination Therapy for Advanced Breast Cancer with Gastric Metastasis--A Case Report].

PubMed

Nakayama, Ichiro; Muranishi, Yumi; Fujita, Yoko

2015-07-01

We report a case of Stage IV breast cancer in a 62-year-old woman who responded well to alternate-day S-1/letrozole combination therapy. She was admitted to our hospital because of appetite loss and vomiting, and was diagnosed with invasive lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal stenting was performed, we initiated oral administration of S-1 (100 mg/body) and letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we administered S-1 on alternate days. Computed tomography and endoscopic examination revealed that the patient has been showing partial response since 1 year after initiating treatment. Therefore, we conclude that alternate-day S-1/letrozole combination therapy could be an effective and sustainable treatment for advanced ER-positive, HER2-negative breast cancer.

Targeted Drug and Gene Delivery Systems for Lung Cancer Therapy

PubMed Central

Sundaram, Sneha; Trivedi, Ruchit; Durairaj, Chandrasekar; Ramesh, Rajagopal; Ambati, Balamurali K.; Kompella, Uday B.

2009-01-01

Purpose To evaluate the efficacy of a novel docetaxel derivative of deslorelin, a luteinizing hormone releasing hormone (LHRH) agonist, and its combination in-vivo with RGD peptide conjugated nanoparticles encapsulating an anti-angiogenic, anti-VEGF intraceptor (Flt23k) (RGD-Flt23k-NP) in H1299 lung cancer cells and/or xenografts in athymic nude BALB/c mice. Experimental Design The in-vitro and in-vivo efficacy of the deslorelin-docetaxel conjugate (D-D) was evaluated in H1299 cells and xenografts in athymic nude mice. Co-administration of D-D and RGD-Flt23k-NP was tested in-vivo in mice. Tumor inhibition, apoptosis and VEGF inhibition were estimated in each of the treatment groups. Results The conjugate enhanced in-vitro docetaxel efficacy by 13-fold in H1299 cells compared to docetaxel at 24h, and this effect was inhibited following reduction of LHRH-receptor expression by an antisense oligonucleotide. Combination of the conjugate with the RGD-Flt23k-NP in-vivo resulted in an 82- and 15-fold tumor growth inhibition on day 39 following repeated weekly intravenous injections and a single intratumoral injection, respectively. These effects were significantly greater than individual targeted therapies or docetaxel alone. Similarly, apoptotic indices for the combination therapy were 14 and 10% in the intravenous and intratumoral groups, respectively, and higher than the individual therapies. Combination therapy groups exhibited greater VEGF inhibition in both the intravenous and intratumoral groups. Conclusions Docetaxel efficacy was enhanced by LHRH-receptor targeted deslorelin conjugate and further improved by combination with targeted anti-angiogenic nanoparticle gene therapy. Combination of novel targeted therapeutic approaches described here provides an attractive alternative to the current treatment options for lung cancer therapy. PMID:19920099

Optimization of combination therapy of arsenic trioxide and fractionated radiotherapy for malignant glioma

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

Ning Shoucheng; Knox, Susan J.

2006-06-01

Purpose: The primary objective was to optimize the combined treatment regimen using arsenic trioxide (ATO) and fractionated radiotherapy for the treatment of malignant glioma. Methods and Materials: Nude mice with human glioma xenograft tumors were treated with fractionated local tumor radiation of 250 cGy/fraction/day and 5 mg/kg ATO for 5-10 days. Results: Time course experiments demonstrated that maximal tumor growth delay occurred when ATO was administered between 0 and 4 h after radiation. The combination treatment of ATO and radiation synergistically inhibited tumor growth and produced a tumor growth delay time of 13.2 days, compared with 1.4 days and 6.5more » days for ATO and radiation alone (p < 0.01), respectively. The use of concurrent therapy of radiation and ATO initially, followed by ATO as maintenance therapy, was superior to the use of preloading with ATO before combined therapy and produced a tumor growth delay time of 22.7 days as compared with 11.7 days for the ATO preloading regimen (p < 0.01). The maintenance dose of ATO after concurrent therapy was effective and important for continued inhibition of tumor growth. Conclusions: The combined use of fractionated radiation and ATO is effective for the treatment of glioma xenograft tumors. ATO was most effective when administered 0-4 h after radiation without pretreatment with ATO. These results have important implications for the optimization of treatment regimen using ATO and fractionated radiotherapy for the treatment of brain tumors.« less

Clinical evidence and mechanistic basis for vildagliptin’s effect in combination with insulin

PubMed Central

Schweizer, Anja; Foley, James E; Kothny, Wolfgang; Ahrén, Bo

2013-01-01

Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with vildagliptin, metformin, and basal insulin could be an attractive therapeutic option. PMID:23431062

High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

USDA-ARS?s Scientific Manuscript database

Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

[Combination drug therapy in patients with BPH].

PubMed

Kuzmenko, A V; Kuzmenko, V V; Gyaurgiev, T A

2018-03-01

Introuction. One of the risk factors for LUTS is an infravesical obstruction, which is most often caused by benign prostatic hyperplasia (BPH). BPH symptoms are formed due to three components: static (mechanical), dynamic, and impaired functional capacity of the bladder. Medical treatment with 1-blockers decreases the outflow obstruction. 5-alpha reductase inhibitors are used to inhibit the static component of BPH. To investigate the effectiveness of various modifications of medical therapy of BPH using -blockers and 5-reductase inhibitors and combinations thereof. The study comprised 90 BPH patients who were divided into three groups, with each group containing 30 people. Patients of group I, II and III received monotherapy with -blockers, a combination of 5-reductase and -blockers, and fixed-dose combination drug Duodart, respectively. Evaluation of the treatment effectiveness included filling out voiding diaries, completing the I-PSS and QL questionnaires, uroflowmetry, transrectal ultrasonography of the prostate and estimation of the incidence of adverse effects. Also, compliance with the treatment was evaluated, and the number of patients who had episodes of acute urinary retention and required surgical treatment during the 12 month treatment course was registered. Compared to monotherapy, combination therapy with -blockers and 5-reductase inhibitors more effectively reduces the LUTS, increases Qmax and prevents the disease progression, which manifests in a lower incidence of AUR and fewer surgical interventions in groups II and III. However, the combination therapy can be associated with some side effects. Patients who received fixed-dose combination drug Duodart had a greater compliance rate than patients on the combination of drugs, which, in our opinion, is associated with fewer cases of AUR and surgical interventions. The use of Duodart in patients with BPH effectively alleviates LUTS and reduces the risk of the disease progression, which manifests itself in a reduced number of complications and thereby contributes to improving the quality of life of patients.

Synergistic combination dry powders for inhaled antimicrobial therapy

NASA Astrophysics Data System (ADS)

Heng, Desmond; Lee, Sie Huey; Teo, Jeanette; Ng, Wai Kiong; Chan, Hak-Kim; Tan, Reginald B. H.

2013-06-01

Combination products play an important role in medicine as they offer improved clinical effectiveness, enhanced patient adherence, and reduced administrative costs. In combination antimicrobial therapy, the desired outcome is to extend the antimicrobial spectrum and to achieve a possible synergistic effect. However, adverse antagonistic species may sometimes emerge from such combinations, leading to treatment failure. Therefore, it is crucial to screen the drug candidates for compatibility and possible antagonistic interactions. This work aims to develop a novel synergistic dry powder inhaler (DPI) formulation for antimicrobial combination therapy via the pulmonary route. Binary and ternary combinations were prepared via spray drying on a BUCHI® Nano Spray Dryer B-90. All powders were within the respirable size range, and were consisted of spherical particles that were slightly corrugated. The powers yielded fine particle fractions (of the loaded dose) of over 40% when dispersed using an Aerolizer® DPI at 60 L/min. Time-kill studies carried out against common respiratory tract pathogenic bacteria Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumonia and Acinetobacter baumannii at 1x the minimum inhibitory concentration (MIC) over 24 hours revealed no antagonistic behavior for both combinations. While the interactions were generally found to be indifferent, a favorable synergistic effect was detected in the binary combination when it was tested against Pseudomonas aeruginosa bacteria.

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

PubMed

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

2011-09-01

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

Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence.

PubMed

Else, Monica; Dearden, Claire E; Matutes, Estella; Forconi, Francesco; Lauria, Francesco; Ahmad, Humayun; Kelly, Susan; Liyanage, Anandika; Ratnayake, Vijitha; Shankari, Jagadeesan; Whalley, Ioana; Catovsky, Daniel

2011-06-01

The purine analogs pentostatin and cladribine are effective treatments for hairy cell leukemia (HCL). However, alternative treatments are needed for patients with recurrent disease. We reviewed retrospectively data from 18 patients who were retreated with either pentostatin (n = 12) or cladribine (n = 6) in combination with rituximab, after 1-6 (median 2) previous treatments with either purine analog as a single agent. All 18 patients responded to therapy, with a complete response (CR) rate of 89%. This compared favorably with CR rates of 68% after second-line therapy and 47% after third-line therapy in 88 patients retreated one or more times with a purine analog alone. Toxicity with the combination treatment was minimal. At a median follow-up of 36 months (range 5-83 months) all 16 complete responders remained in CR, while one partial responder developed recurrent disease at 10 months. The estimated recurrence rate at 3 years was 7%. This compares with 21% after second-line therapy and 42% after third-line therapy in the 88 patients retreated with a purine analog alone. Furthermore, it was a marked improvement on the 55% recurrence at 3 years previously seen in these same 18 patients after their own first-line treatment with single-agent pentostatin or cladribine (p = 0.006). The combination of a purine analog with rituximab was safe and effective for patients with recurrent HCL. The results suggest an added benefit compared with single-agent purine analog therapy.

Conjugated polymer and drug co-encapsulated nanoparticles for Chemo- and Photo-thermal Combination Therapy with two-photon regulated fast drug release

NASA Astrophysics Data System (ADS)

Yuan, Youyong; Wang, Zuyong; Cai, Pingqiang; Liu, Jie; Liao, Lun-De; Hong, Minghui; Chen, Xiaodong; Thakor, Nitish; Liu, Bin

2015-02-01

The spatial-temporal synchronization of photothermal therapy and chemotherapy is highly desirable for an efficient cancer treatment with synergistic effect. Herein, we developed a chemotherapeutic drug doxorubicin (DOX) and photothermal conjugated polymer (CP) co-loaded nanoplatform using a near-infrared (NIR) laser responsive amphiphilic brush copolymer as the encapsulation matrix. The obtained nanoparticles (NPs) exhibit good monodispersity and excellent stability, which can efficiently convert laser energy into thermal energy for photothermal therapy. Moreover, the hydrophobic polymer matrix bearing a number of 2-diazo-1,2-naphthoquinones (DNQ) moieties could be transformed to a hydrophilic one upon NIR two-photon laser irradiation, which leads to fast drug release. Furthermore, the surface modification of the NPs with cyclic arginine-glycine-aspartic acid (cRGD) tripeptide significantly enhances the accumulation of the NPs within integrin αvβ3 overexpressed cancer cells. The half-maximal inhibitory concentration (IC50) of the combination therapy is 13.7 μg mL-1, while the IC50 for chemotherapy and photothermal therapy alone is 147.8 μg mL-1 and 36.2 μg mL-1, respectively. The combination index (C.I.) is 0.48 (<1), which indicates the synergistic effect for chemotherapy and PTT. These findings provide an excellent NIR laser regulated nanoplatform for combined cancer treatment with synergistic effect due to the synchronous chemo- and photo-thermal therapy.

Combination effect of oncolytic adenovirus therapy and herpes simplex virus thymidine kinase/ganciclovir in hepatic carcinoma animal models

PubMed Central

Zheng, Fei-qun; Xu, Yin; Yang, Ren-jie; Wu, Bin; Tan, Xiao-hua; Qin, Yi-de; Zhang, Qun-wei

2009-01-01

Aim: Oncolytic adenovirus, also called conditionally replicating adenovirus (CRAD), can selectively propagate in tumor cells and cause cell lysis. The released viral progeny can infect neighboring cancer cells, initiating a cascade that can lead to the ultimate destruction of the tumor. Suicide gene therapy using herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) offers a potential treatment strategy for cancer and is undergoing preclinical trials for a variety of tumors. We hypothesized that HSV-TK gene therapy combined with oncolytic adenoviral therapy would have an enhanced effect compared with the individual effects of the therapies and is a potential novel therapeutic strategy to treat liver cancer. Methods: To address our hypothesis, a novel CRAD was created, which consisted of a telomerase-dependent oncolytic adenovirus engineered to express E1A and HSV-TK genes (Ad-ETK). The combined effect of Ad-ETK and GCV was assessed both in vitro and in vivo in nude mice bearing HepG2 cell-derived tumors. Expression of the therapeutic genes by the transduced tumor cells was analyzed by RT-PCR and Western blotting. Results: We confirmed that Ad-ETK had antitumorigenic effects on human hepatocellular carcinoma (HCC) both in vitro and in vivo, and the TK/GCV system enhanced oncolytic adenoviral therapy. We confirmed that both E1A and HSV-TK genes were expressed in vivo. Conclusion: The Ad-ETK construct should provide a relatively safe and selective approach to killing cancer cells and should be investigated as an adjuvant therapy for hepatocellular carcinoma. PMID:19363518

Observation of combined/optimized therapy of Lamivudine and Adefovir Dipivoxyl for hepatitis B-induced decompensated cirrhosis with baseline HBV DNA>1,000 IU/mL.

PubMed

Zhang, D; Zhao, G; Li, L; Li, Z

2017-01-01

This study aimed to observe and compare the efficacy and safety of the combined therapy and two different optimized therapies of lamivudine (LAM) and adefovir dipivoxil (ADV), as well as entecavir (ETV) monotherapy in patients with hepatitis B-induced decompensated cirrhosis. Method : A total of 127 patients with decompensated cirrhosis were divided into four groups, and each group received different doses of regimens: initial combination of LAM and ADV, ADV add-on therapies with previous 12-week LAM, ADV add-on therapies with previous 24-week LAM, and ETV monotherapy. At the end of the treatment, the level of alanine amino-transferase (ALT), albumin (ALB) and total bilirubin (TBIL) in the combination therapy group and 12-week optimized therapy group were significantly improved. For the 24-week optimized therapy group, only ALT levels revealed a significant improvement. There were no obvious differences in the normalization rate of ALT, negative conversion rate of HBV DNA and HBeAg, as well as improvement in Child-Pugh scores among the combination therapy group, 12-week optimized therapy group, and ETV monotherapy group. However, the difference among these three groups and the 24-week optimized therapy group were significant. Differences were not observed in the HBeAg seroconversion between each group. Differences in blood urea nitrogen, serum creatinine, creatine kinase, or other serious adverse effects were not observed in each group at the end of the 96-week treatment. Combination therapy and early ADV addition were the preferred approaches in the antiviral strategy for the treatment of hepatitis B-induced decompensated cirrhosis.

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

ERIC Educational Resources Information Center

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

2017-01-01

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

Evaluating Nicotine Replacement Therapy and Stage-Based Therapies in a Population-Based Effectiveness Trial

ERIC Educational Resources Information Center

Velicer, Wayne F.; Friedman, Robert H.; Fava, Joseph L.; Gulliver, Suzy B.; Keller, Stefan; Sun, Xiaowu; Ramelson, Harley; Prochaska, James O.

2006-01-01

Pharmacological interventions for smoking cessation are typically evaluated using volunteer samples (efficacy trials) but should also be evaluated in population-based trials (effectiveness trials). Nicotine replacement therapy (NRT) alone and in combination with behavioral interventions was evaluated on a population of smokers from a New England…

Combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation versus placebo in type 2 diabetes.

PubMed

Bay, Roohallah; Bay, Fatemeh

2011-09-01

Type 2 diabetes is one of the most widespread diseases in the world. The main aim of this research was to evaluate the effect of combined therapy using acupressure therapy, hypnotherapy, and transcendental meditation (TM) on the blood sugar (BS) level in comparison with placebo in type 2 diabetic patients. We used "convenience sampling" for selection of patients with type 2 diabetes; 20 patients were recruited. For collection of data, we used an identical quasi-experimental design called "nonequivalent control group." Therapy sessions each lasting 60-90 min were carried out on 10 successive days. We prescribed 2 capsules (containing 3g of wheat flour each) for each member of the placebo group (one for evening and one for morning). Pre-tests, post-tests, and follow-up tests were conducted in a medical laboratory recognized by the Ministry of Health and Medical Education of Iran. Mean BS level in the post-tests and follow-up tests for the experimental group was reduced significantly in comparison with the pre-tests whereas in the placebo group no changes were observed. Combined therapy including acupressure therapy, hypnotherapy, and TM reduced BS of type 2 diabetic patients and was more effective than placebo therapy on this parameter. Copyright © 2011. Published by Elsevier B.V.

Rapamycin/IL-2 combination therapy in patients with type 1 diabetes augments Tregs yet transiently impairs β-cell function.

PubMed

Long, S Alice; Rieck, Mary; Sanda, Srinath; Bollyky, Jennifer B; Samuels, Peter L; Goland, Robin; Ahmann, Andrew; Rabinovitch, Alex; Aggarwal, Sudeepta; Phippard, Deborah; Turka, Laurence A; Ehlers, Mario R; Bianchine, Peter J; Boyle, Karen D; Adah, Steven A; Bluestone, Jeffrey A; Buckner, Jane H; Greenbaum, Carla J

2012-09-01

Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.

Systematic review on randomized controlled clinical trials of acupuncture therapy for neurovascular headache.

PubMed

Zhao, Lei; Guo, Yi; Wang, Wei; Yan, Li-juan

2011-08-01

To evaluate the effectiveness of acupuncture as a treatment for neurovascular headache and to analyze the current situation related to acupuncture treatment. PubMed database (1966-2010), EMBASE database (1986-2010), Cochrane Library (Issue 1, 2010), Chinese Biomedical Literature Database (1979-2010), China HowNet Knowledge Database (1979-2010), VIP Journals Database (1989-2010), and Wanfang database (1998-2010) were retrieved. Randomized or quasi-randomized controlled studies were included. The priority was given to high-quality randomized, controlled trials. Statistical outcome indicators were measured using RevMan 5.0.20 software. A total of 16 articles and 1 535 cases were included. Meta-analysis showed a significant difference between the acupuncture therapy and Western medicine therapy [combined RR (random efficacy model)=1.46, 95% CI (1.21, 1.75), Z=3.96, P<0.0001], indicating an obvious superior effect of the acupuncture therapy; significant difference also existed between the comprehensive acupuncture therapy and acupuncture therapy alone [combined RR (fixed efficacy model)=3.35, 95% CI (1.92, 5.82), Z=4.28, P<0.0001], indicating that acupuncture combined with other therapies, such as points injection, scalp acupuncture, auricular acupuncture, etc., were superior to the conventional body acupuncture therapy alone. The inclusion of limited clinical studies had verified the efficacy of acupuncture in the treatment of neurovascular headache. Although acupuncture or its combined therapies provides certain advantages, most clinical studies are of small sample sizes. Large sample size, randomized, controlled trials are needed in the future for more definitive results.

A Systematic Review of the Combined Use of Electroconvulsive Therapy and Psychotherapy for Depression

PubMed Central

McClintock, Shawn M.; Brandon, Anna R.; Husain, Mustafa M.; Jarrett, Robin B.

2011-01-01

Objective Electroconvulsive therapy (ECT) is one of the most effective treatments for severe Major Depressive Disorder (MDD). However, after acute phase treatment and initial remission, relapse rates are significant. Strategies to prolong remission include continuation phase ECT, pharmacotherapy, psychotherapy, or their combinations. This systematic review synthesizes extant data regarding the combined use of psychotherapy with ECT for the treatment of patients with severe MDD and offers the hypothesis that augmenting ECT with depression-specific psychotherapy represents a promising strategy for future investigation. Methods The authors performed two independent searches in PsychInfo (1806 – 2009) and MEDLINE (1948 – 2009) using combinations of the following search terms: Electroconvulsive Therapy (including ECT, ECT therapy, electroshock therapy, EST, shock therapy) and Psychotherapy (including cognitive behavioral, interpersonal, group, psychodynamic, psychoanalytic, individual, eclectic, and supportive). We included in this review a total of six articles (English language) that mentioned ECT and psychotherapy in the abstract, and provided a case report, series, or clinical trial. We examined the articles for data related to ECT and psychotherapy treatment characteristics, cohort characteristics, and therapeutic outcome. Results Although research over the past seven decades documenting the combined use of ECT and psychotherapy is limited, the available evidence suggests that testing this combination has promise and may confer additional, positive functional outcomes. Conclusions Significant methodological variability in ECT and psychotherapy procedures, heterogeneous patient cohorts, and inconsistent outcome measures prevent strong conclusions; however, existing research supports the need for future investigations of combined ECT and psychotherapy in well-designed, controlled clinical studies. Depression-specific psychotherapy approaches may need special adaptations in view of the cognitive effects following ECT. PMID:21206376

Repaglinide in combination therapy.

PubMed

Moses, R

2002-12-01

Type 2 diabetes mellitus (T2DM) is a progressive disorder requiring increasingly aggressive treatment to achieve and maintain target blood glucose concentrations in the presence of deteriorating insulin secretion and increasing insulin resistance. Diet and lifestyle modification are often sufficient initially; however, most patients eventually require pharmacological intervention. With disease progression, monotherapy becomes less effective, so combination therapy is required, using drugs with complementary modes of action to maximise glycaemic control. The prandial glucose regulator repaglinide has been studied in combination with metformin (an inhibitor of hepatic glucose production), neutral protamine Hagedorn (NPH)-insulin (which has a long duration of effect, but at the risk of early hypoglycaemia and late hyperglycaemia in the dosing interval) and three thiazolidinediones (TZDs--troglitazone, rosiglitazone and pioglitazone, which stimulate nuclear receptors to increase insulin sensitivity and reduce insulin resistance) in patients whose diabetes was inadequately controlled by previous monotherapy or combination therapy. The combination of repaglinide and metformin resulted in reduced fasting plasma glucose concentrations (by 2.2 mmol/l) and HbA1c (by 1.4%). Combination therapy with repaglinide and bedtime NPH-insulin resulted in reductions in fasting plasma glucose (by 5.4 mmol/l) and HbA1c (by 0.7%). The combination of repaglinide and each TZD also resulted in consistent decreases in fasting plasma glucose concentrations and HbA1c. No severe hypoglycaemic episodes were reported in the three studies. In conclusion, repaglinide has additive, and often synergistic, effects on glycaemic control when given in combination regimens and should be a valuable option in the management of patients with T2DM.

Population-based pharmacoeconomic model for adopting capecitabine/docetaxel combination treatment for anthracycline-pretreated metastatic breast cancer.

PubMed

Verma, Shailendra; Ilersich, A Lane

2003-01-01

To model the cost-effectiveness of adopting capecitabine/docetaxel combination therapy in place of single-agent taxane therapy for women in the province of Ontario, Canada, receiving treatment for anthracycline-pretreated metastatic breast cancer. Clinical effectiveness and economic data were combined in a population model, from the perspective of a universal health care system. Estimates of clinical effectiveness and medical resource utilization were derived prospectively during a phase III randomized controlled trial comparing single-agent docetaxel with capecitabine/docetaxel combination therapy. Population data were obtained from the Cancer Care Ontario Registry and provincial prescription claims data. During 1999-2000, 542 patients were eligible for taxane monotherapy. As capecitabine/docetaxel treatment confers a median 3-month survival benefit compared with docetaxel monotherapy, the projected survival gain in these patients was 136 life-years. The results of the cost-effectiveness analysis demonstrate that the survival benefit provided by the addition of capecitabine to single-agent docetaxel is afforded at a small incremental cost of Canadian $3,691 per life-year gained. Hospitalization costs for treatment of adverse events were less for patients receiving capecitabine/docetaxel combination therapy than for those receiving docetaxel monotherapy. The results were robust for adjustments in treatment costs and adverse effects costs. Due to its 3-month survival gain and small incremental treatment cost, capecitabine/docetaxel is judged to be a highly cost-effective treatment in anthracycline-pretreated advanced breast cancer. From the perspective of the Ontario health care system, the addition of capecitabine to docetaxel in this patient population is a clinically appropriate and economically acceptable treatment strategy.

Novel Synergistic Protective Efficacy of Atovaquone and Diclazuril on Fetal-Maternal Toxoplasmosis

PubMed Central

Oz, Helieh S.

2014-01-01

Over 1 billion people globally are estimated to be infected with Toxoplasma gondii with severe or unknown consequences and no safe and effective therapies are available against congenital or persistent chronic infection. We propose that atovaquone and diclazuril synergistically protect against fetal-maternal toxoplasmosis. Methods Programmed pregnant mice were treated with atovaquone and diclazuril monotherapy, or combined (atovaquone + diclazuril) therapy and infected with tachyzoites (0, 300, 600) and the course of infection was studied. Results Infected dams with low dose (300) developed moderate toxoplasmosis complications and treatments were similarly effective with minor differences between monotherapies. In contrast, major differences were observed amongst varied treatments during high-dose (600) infection and severe related- toxoplasmosis complications as follows. Dams developed hydrothorax, ascities and excess weight gain. Combined therapy (P < 0.01) and to a lesser extent diclazuril monotherapy (P < 0.05) protected dams from excess weight, hydrothorax, and ascities. Infected dams exhibited splenomegaly, hepatomegaly and severe hepatitis. Combined therapy synergistically normalized pathology (P < 0.001) and to a lesser degree monotherapy (diclazuril P < 0.01, and atovaquone P < 0.05) protected dams from hepatitis and splemomegaly. Additionally, behavioral response to pain stimuli and fetal weight and fetal numbers were significantly preserved in treated dams Conclusions This is the first report describing combined atovaquone and diclazuril therapy (a) to be safe in pregnancy, (b) to exert novel synergistic effects, and (c) to protect dams and their nested fetuses against adverse effects of severe toxoplasmosis. PMID:25210646

Diabetic and Nondiabetic Gastroparesis.

PubMed

McCallum; Brown

1998-12-01

Nutritional support is essential in treating patients with gastroparesis. Initially, dietary changes should be instituted to reduce extra fat and bulk, and patients should be encouraged to eat frequent small meals with liquid supplementation. Enteral feeding should be introduced in the event of weight loss or persistent vomiting. Medical therapy is usually necessary early in treatment. Cisapride is the initial agent of choice and may be combined with an antiemetic agent, such as promethazine or chlorpromazine or, if side effects occur, ondansetron and granesitron. If cisapride is ineffective or contraindicated, metoclopramide is a reasonable option, though limited by side effects. Erythromycin is useful in the acute treatment of postoperative ileus and hospitalized gastroparetic patients, but its role is limited based on concerns about poor long-term effectiveness and antimicrobial resistance. Once domperidone becomes available in the United States, it will be useful for its promotility and antiemetic qualities. Combination therapy should be considered if monotherapy with cisapride or metoclopramide alone is ineffective. While not yet well studied, combination therapy has the potential to offer dramatic benefit for patients with refractory gastroparesis. Metoclopramide may be added to cisapride for patients with breakthrough symptoms or refractory chronic symptoms. Other combinations include metoclopramide with erythromycin, domperidone with cisapride, and domperidone with erythromycin. In the future, gastric pacing may become an effective option for patients not responding to medical therapy. Total gastrectomy should be performed only for end-stage gastroparesis when all other therapy has failed. Both procedures should be reserved for centers that specialize in severe gastric motility disorders.

New Enzyme Prodrug and Methionine-Depletion Combination Therapy of Breast Cancer Designed for Effective Delivery to the Tumor

DTIC Science & Technology

2011-10-01

effects since the drug is produced locally in the tumor and the pro drug concentration would be at a le- vel that would not affect cells in other tissues...Depletion Combination Therapy of Breast Cancer Designed for Effective Delivery to the Tumor Roger Harrison University of Oklahoma Norman, OK 73019 15...SEP 2010 - 14 SEP 2011Annual01-10-2011 Recombinant L-methioninase-annexin V and cytosine deaminase-annexin V fusion proteins have been produced in

Evaluation of trimethoprim-sulfamethoxazole based combination therapy against Stenotrophomonas maltophilia: in vitro effects and clinical efficacy in cancer patients.

PubMed

Araoka, Hideki; Baba, Masaru; Okada, Chikako; Abe, Masahiro; Kimura, Muneyoshi; Yoneyama, Akiko

2017-05-01

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models

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

Koonce, Nathan A.; Quick, Charles M.; Hardee, Matthew E.

Purpose: Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. Methods and Materials: The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. Results: In the 4T1 murine breast tumormore » model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose—notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Conclusions: Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation therapy is effective in reducing IFP and tumor growth and shows promise for clinical translation.« less

When sepsis persists: a review of MRSA bacteraemia salvage therapy.

PubMed

Kullar, Ravina; Sakoulas, George; Deresinski, Stan; van Hal, Sebastiaan J

2016-03-01

MRSA bacteraemia (MRSAB), including infective endocarditis, carries a high mortality rate, with up to 50% of patients failing initial therapy with vancomycin and requiring salvage therapy. Persistent MRSAB can be difficult to successfully eliminate, especially when source control is not possible due to an irremovable focus or the bacteraemia still persists despite surgical intervention. Although vancomycin and daptomycin are the only two antibiotics approved by the US FDA for the treatment of patients with MRSAB as monotherapy, the employment of novel strategies is required to effectively treat patients with persistent MRSAB and these may frequently involve combination drug therapy. Treatment strategies that are reviewed in this manuscript include vancomycin combined with a β-lactam, daptomycin-based therapy, ceftaroline-based therapy, linezolid-based therapy, quinupristin/dalfopristin, telavancin, trimethoprim/sulfamethoxazole-based therapy and fosfomycin-based therapy. We recommend that combination antibiotic therapy be considered for use in MRSAB salvage treatment. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

[Classical antihypertensive drugs: diuretics].

PubMed

Nagy, Viktor László

2017-03-01

The diuretics are essential medicaments of antihypertensive therapy. They reduce blood pressure and cardiovascular events optimally. With increasing doses of thiazides and thiazide analogs do not come further powerful effect of reducing blood pressure or cardiovascular mortality and morbidity, but clearly elevate the side effects. Because of it, the minimum effective dose level and the fixed-dose combination therapy should be preferred. The use these drugs leads to especially positive outcome in elder patients, isolated systolic hypertension, heart failure, after stroke and in black population. Loop diuretics as antihypertensive therapy can be used only by renal impairment. The use of aldosterone antagonists can have a good effect not only on heart failure but also on prevention of atrial fibrillation. Furthermore, using it in a combination therapy with thiazides, it reduces the risk of hypokalemia. Therefore, the diuretic treatment in hypertension is flourishing again. Orv. Hetil., 2017, 158(11), 403-408.

Manual therapy, exercise therapy or combined treatment in the management of adult neck pain - A systematic review and meta-analysis.

PubMed

Fredin, Ken; Lorås, Håvard

2017-10-01

Neck pain is a common and often disabling musculoskeletal condition. Two therapies frequently prescribed for its management are manual therapy (MT) and exercise therapy (ET), and combining these treatment approaches are common. To assess whether or not combined treatment consisting of MT and ET is more effective than either therapy alone in relieving pain and improving function in adult patients with grade I-II neck pain. Systematic review with meta-analysis. A systematic search on EMBASE, MEDLINE, AMED, CENTRAL and PEDro were performed until June 2017. Randomized controlled trials with adult grade I-II neck pain patients were included if they investigated the combined effect of MT and ET to the same ET or MT alone, and reported pain intensity or disability on numerical scales. Quality of life was assessed as a secondary outcome. Quality of the included trials was assessed with the PEDro scale, and the quality of evidence was assessed with GRADE. 1169 articles were screened, and 7 studies were included, all of which investigated the addition of ET to MT. Only very small and non-significant between group differences was found on pain intensity at rest, neck disability, and quality of life at immediate post-treatment, 6 months, and 12 months follow-up. The quality of evidence was moderate for pain-at-rest outcomes and moderate too low for neck disability and quality of life outcomes. Combined treatment consisting of MT and ET does not seem to be more effective in reducing neck pain intensity at rest, neck disability or improving quality of life in adult patients with grade I-II neck pain, than ET alone. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dopamine D2 receptor antagonist sulpiride enhances dexamethasone responses in the treatment of drug-resistant and metastatic breast cancer.

PubMed

Li, Jian; Yao, Qing-Yu; Xue, Jun-Sheng; Wang, Li-Jie; Yuan, Yin; Tian, Xiu-Yun; Su, Hong; Wang, Si-Yuan; Chen, Wen-Jun; Lu, Wei; Zhou, Tian-Yan

2017-09-01

Recent evidence shows that dopamine D2-like receptor (D2DR) antagonists, such as trifluoperazine and thioridazine, are effective for cancer therapy and inhibition of cancer stem-like cells (CSCs). In this study, we investigated the anti-cancer effects of combination therapy of dexamethasone (DEX) and sulpiride (SUL), an atypical antipsychotic, against drug-resistant and metastatic breast cancers and further explored the underlying mechanisms. Oral administration of SUL (25, 100 mg·kg -1 ·d -1 ) alone did not inhibit the tumor growth in human breast cancer MCF-7/Adr xenograft model, but dose-dependently decreased the proportion of CSCs in vitro and in vivo. In contrast, combination therapy of SUL (50 mg·kg -1 ·d -1 ) and DEX (8 mg·kg -1 ·d -1 ) markedly suppressed the tumor growth in MCF-7/Adr xenograft model with little systemic toxicity and lung metastasis in murine metastatic breast cancer 4T1 xenograft model. Among the metastasis-associated biomarkers analyzed, the combination therapy significantly decreased the levels of MMP-2, but increased E-cadherin levels in 4T1 xenograft tumors. Moreover, the combination therapy significantly inhibited the cell colony formation, migration and invasion of 4T1 and human breast cancer MDA-MB-231 cells in vitro. Addition of a specific D2DR agonist 7-OH-DPAT to the combination therapy reversed the enhanced anti-cancer effects in vivo and CSC population loss in tumor tissues. Our data demonstrate that SUL remarkably enhances the efficacy of DEX in the treatment of drug-resistant and metastatic breast cancer via the antagonism of D2DR, which might result from the eradication of CSCs.

Cisplatin and photodynamic therapy exert synergistic inhibitory effects on small-cell lung cancer cell viability and xenograft tumor growth

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

Chen, You-Shuang; Peng, Yin-Bo; Yao, Min

Lung cancer is the leading cause of cancer death worldwide. Small-cell lung cancer (SCLC) is an aggressive type of lung cancer that shows an overall 5-year survival rate below 10%. Although chemotherapy using cisplatin has been proven effective in SCLC treatment, conventional dose of cisplatin causes adverse side effects. Photodynamic therapy, a form of non-ionizing radiation therapy, is increasingly used alone or in combination with other therapeutics in cancer treatment. Herein, we aimed to address whether low dose cisplatin combination with PDT can effectively induce SCLC cell death by using in vitro cultured human SCLC NCI-H446 cells and in vivo tumor xenograft model.more » We found that both cisplatin and PDT showed dose-dependent cytotoxic effects in NCI-H446 cells. Importantly, co-treatment with low dose cisplatin (1 μM) and PDT (1.25 J/cm{sup 2}) synergistically inhibited cell viability and cell migration. We further showed that the combined therapy induced a higher level of intracellular ROS in cultured NCI-H446 cells. Moreover, the synergistic effect by cisplatin and PDT was recapitulated in tumor xenograft as revealed by a more robust increase in the staining of TUNEL (a marker of cell death) and decrease in tumor volume. Taken together, our findings suggest that low dose cisplatin combination with PDT can be an effective therapeutic modality in the treatment of SCLC patients.« less

Spatially Uniform Tumor Treatment and Drug Penetration by Regulating Ultrasound with Microbubbles.

PubMed

Ho, Yi-Ju; Wang, Tzu-Chia; Fan, Ching-Hsiang; Yeh, Chih-Kuang

2018-05-30

Tumor microenvironment has different morphologies of vessels in the core and rim regions, which influences the efficacy of tumor therapy. Our study proposed to improve the spatial uniformity of the antivascular effect and drug penetration within the tumor core and rim in combination therapies by regulating ultrasound-stimulated microbubble destruction (USMD). Focused ultrasound at 2 MHz and lipid-shell microbubbles (1.12 ± 0.08 μm, mean ± standard deviation) were used to perform USMD. The efficiency of the antivascular effect was evaluated by intravital imaging to determine the optimal USMD parameters. Tumor perfusion and histological alterations in the tumor core and rim were used to analyze the spatial uniformity of the antivascular effect and liposomal-doxorubicin (5 mg/kg) penetration in the combination therapy. Tumor vessels of specific sizes were disrupted by regulating USMD: vessels with sizes of 11 ± 3, 14 ± 5, 19 ± 7, and 23 ± 10 μm were disrupted by stimulation at acoustic pressures of 3, 5, 7, and 9 MPa, respectively (each p < 0.05). The effective treatment time of USMD (at 2 × 10 7 microbubbles/mouse, 7 MPa, and three cycles) was 60-120 min, which resulted in the disruption of 21-44% of vessels smaller than 50 μm. The reductions in perfusion and vascular density after combination therapy did not differ significantly between the tumor core and rim. This study found that regulating USMD can result in homogeneous antivascular effects and drug penetration within tumors and thereby improve the efficacy of combination therapies.

Tumor therapy with a urokinase plasminogen activator-activated anthrax lethal toxin alone and in combination with paclitaxel

PubMed Central

Wein, Alexander N.; Liu, Shihui; Zhang, Yi; McKenzie, Andrew T.; Leppla, Stephen H.

2013-01-01

PA-U2, an engineered anthrax protective antigen that is activated by urokinase was combined with wild-type lethal factor in the treatment of Colo205 colon adenocarcinoma in vitro and B16-BL6 mouse melanoma in vitro and in vivo. This therapy was also tested in combination with the small molecule paclitaxel, based on prior reports suggesting synergy between ERK1/2 inhibition and chemotherapeutics. Colo205 was sensitive to PA-U2/LF while B16-BL6 was not. For the combination treatment of B16-BL6, paclitaxel showed a dose response in vitro, but cells remained resistant to PA-U2/LF even in the presence of paclitaxel. In vivo, each therapy slowed tumor progression, and an additive effect between the two was observed. Since LF targets tumor vasculature while paclitaxel is an anti-mitotic, it is possible the agents were acting against different cells in the stroma, precluding a synergistic effect. The engineered anthrax toxin PA-U2/LF warrants further development and testing, possibly in combination with an anti-angiogenesis therapy such as sunitinib or sorafinib. PMID:22843210

A Systematic Review of Combination Therapy with Stimulants and Atomoxetine for Attention-Deficit/Hyperactivity Disorder, Including Patient Characteristics, Treatment Strategies, Effectiveness, and Tolerability

PubMed Central

Gau, Susan Shur-Fen; Méndez, Luis; Montgomery, William; Monk, Julie A.; Altin, Murat; Wu, Shenghu; Lin, Chaucer C.H.; Dueñas, Héctor J.

2013-01-01

Abstract Objective The purpose of this article was to systematically review the literature on stimulant and atomoxetine combination therapy, in particular: 1) Characteristics of patients with attention-deficit/hyperactivity disorder (ADHD) given combination therapy, 2) treatment strategies used, 3) efficacy and effectiveness, and 4) safety and tolerability. Methods Literature databases (MEDLINE®, EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index Expanded, and SciVerse Scopus) were systematically searched using prespecified criteria. Publications describing stimulant and atomoxetine combination therapy in patients with ADHD or healthy volunteers were selected for review. Exclusion criteria were comorbid psychosis, bipolar disorder, epilepsy, or other psychiatric/neurologic diseases that could confound ADHD symptom assessment, or other concomitant medication(s) to treat ADHD symptoms. Results Of the 16 publications included for review, 14 reported findings from 3 prospective studies (4 publications), 7 retrospective studies, and 3 narrative reviews/medication algorithms of patients with ADHD. The other two publications reported findings from two prospective studies of healthy volunteers. The main reason for prescribing combination therapy was inadequate response to previous treatment. In the studies of patients with ADHD, if reported, 1) most patients were children/adolescents and male, and had a combined ADHD subtype; 2) methylphenidate was most often used in combination with atomoxetine for treatment augmentation or switch; 3) ADHD symptom control was improved in some, but not all, patients; and 4) there were no serious adverse events. Conclusions Published evidence of the off-label use of stimulant and atomoxetine combination therapy is limited because of the small number of publications, heterogeneous study designs (there was only one prospective, randomized controlled trial), small sample sizes, and geographic bias. Existing evidence suggests, but does not confirm, that this drug combination may benefit some, but not all, patients who have tried several ADHD medications without success. PMID:23560600

Elbasvir/Grazoprevir, an Alternative in Antiviral Hepatitis C Therapy in Patients under Amiodarone Treatment

PubMed Central

Weiss, Lina; Wustmann, Kerstin; Semmo, Mariam; Schwerzmann, Markus; Semmo, Nasser

2018-01-01

A sofosbuvir/ledipasvir combination is part of a first-line treatment of hepatitis C. However, in patients concurrently treated with amiodarone, cardiac side effects have been described, resulting in an official warning in 2015 by the American Food and Drug Administration and the European Medicines Agency when combining those substances. This deprived numerous hepatitis C patients with concurrent cardiovascular problems of receiving this highly effective treatment. Here we present a treatment alternative with an elbasvir/grazoprevir regimen, based on our successful treatment of a patient under concurrent amiodarone therapy. Our observations indicate that patients treated with amiodarone can finally benefit from effective antiviral therapy. PMID:29606942

Visually augmented targeted combination light therapy for acne vulgaris: a case report.

PubMed

Yazdi, Alireza; Lyons, Colin-William; Roberts, Niamh

2017-10-31

Acne vulgaris is a common skin disease. Pharmacological modalities for treatment are proven to be efficacious but have limitations. Light therapy for acne vulgaris has shown promise in previous studies. This case report and its accompanying images show how a novel approach of visually augmented high fluence light therapy has been used to good effect. A 26-year-old Caucasian woman with acne vulgaris resistant to treatment with topical therapy underwent three sessions of combination potassium titanyl phosphate laser (532 nm)/neodymium-doped: yttrium aluminum garnet laser (1064 nm) light therapy with visually augmented narrow spot size and high fluence. A 73% reduction in total inflammatory lesions was evident 6 months after the initial treatment. This case report illustrates that there may be utility in this novel approach of narrow spot size, magnification-assisted, high fluence targeted combination laser therapy for inflammatory acne.

Modeling combination therapy for breast cancer with BET and immune checkpoint inhibitors.

PubMed

Lai, Xiulan; Stiff, Andrew; Duggan, Megan; Wesolowski, Robert; Carson, William E; Friedman, Avner

2018-05-07

CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor. The model shows that the two drugs are positively correlated in the sense that the tumor volume decreases as the dose of each of the drugs is increased. The model also considers the effect of the combined therapy on levels of myeloid-derived suppressor cells (MDSCs) and the overexpression of TNF-[Formula: see text], which may predict gastrointestinal side effects of the combination.

Acarbose plus metformin fixed-dose combination in the management of type 2 diabetes.

PubMed

Joshi, Shashank R; Ramachandran, Ambady; Chadha, Manoj; Chatterjee, Sudip; Rathod, Rahul; Kalra, Sanjay

2014-08-01

The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. Concerns in the management of diabetes include drug-induced hypoglycemia, poor control of postprandial blood glucose level and weight gain. A carbohydrate-rich diet can cause more load on the intestinal cells producing α-glucosidase. Many patients need combination treatment based on their level of glycemic control and other associated parameters. In such cases, a therapy that provides effective glycemic control with minimal or no risk of adverse events like hypoglycemia or weight gain is highly desired. The chances of cardiovascular events are high in diabetes patients; hence, medicines providing benefits beyond glycemic control such as reduced cardiovascular risk factors may be ideal in such patients. Current available data are related to the rationale and clinical trials on the fixed-dose combination of acarbose plus metformin in management of type 2 diabetes. Combination therapy is routinely prescribed in the management of T2DM. Drugs with complimentary mechanisms should be used to maximize the efficacy of combination therapy. The combination of metformin and acarbose is a rational therapy because of their different and complimentary mechanisms of action, which provides effective glycemic control with additional cardiovascular benefits and minimizes adverse events.

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

PubMed Central

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

2015-01-01

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

Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

PubMed

Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

2016-06-01

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

Topical treatment and combination approaches for vitiligo: new insights, new developments.

PubMed

Hossani-Madani, A R; Halder, R M

2010-02-01

Despite much research done involving elucidation of the pathogenesis of vitiligo, a precise cause is still not known. Prevalent hypotheses include the autoimmune, genetic, neural, self-destruction, growth factor deficiency, viral, and convergence theories, which have served as the basis for treatment formulation. Topical therapies have been a mainstay of vitiligo treatment, with or without phototherapy. Topical treatments used in the treatment of vitiligo include steroids, calcineurin inhibitors, vitamin D analogues, pseudocatalase, and depigmenting agents. Combination therapies are used to improve the success rate of repigmentation. In this article, we have examined randomized controlled trials utilizing topical treatments used as monotherapy or combination therapy. Although psoralen and khellin can be used as topical agents, used in conjunction with UV radiation, we have not included them in the review due to their inability to be used as monotherapy. We have also excluded less used or ineffective topical agents, such as melagenina, topical phenylalanine, topical L-DOPA, coal tar, anacarcin forte oil and topical minoxidil. According to current guidelines, a less than two month trial of potent or very potent topical corticosteroids or topical calcineurin inhibitors may be used for therapy of localized vitiligo (<20% skin surface area). Combinations of topical corticosteroids with excimer laser and UVA seem to be more effective than steroids alone. Pseudocatalase plus NB-UVB does not seem to be more effective than placebo with NB-UVB. Combinations of vitamin D analogues have varied efficacy based on which type is used and the type of UV light. Efficacy of calcineurin inhibitor combinations also vary based on the type used and UV light combined, with tacrolimus being more effective with excimer laser. Pimecrolimus has been effective with NB-UVB and excimer laser on facial lesions, and microdermabrasion on localized areas.

Pharmacokinetic drug evaluation of talimogene laherparepvec for the treatment of advanced melanoma.

PubMed

Burke, Erin E; Zager, Jonathan S

2018-04-01

Current treatment of advanced melanoma is rapidly changing with the introduction of new and effective therapies including systemic as well as locoregional therapies. An example of one such locoregional therapy is intralesional injection with talimogene laherparepvec (T-VEC). Areas covered: T-VEC has been shown in a number of studies to be an effective treatment for patients with stage IIIB, IIIC and IVM1a melanoma. In this article the effectiveness, pharmacokinetics and safety profile of T-VEC is reviewed. Additionally, new research looking at combinations of T-VEC and systemic immunotherapies is reviewed. Expert opinion: Overall, T-VEC is an easily administered, safe, well tolerated and effective oncolytic viral therapy for the treatment of stage IIIB, IIIC, IVM1a unresectable and injectable metastatic melanoma. Recently published studies are showing promising results when T-VEC is combined with systemic therapy and this may be the way of the not too distant future in how we treat metastatic melanoma. Continued work regarding the use of T-VEC with other systemic agents will provide new and more effective treatment strategies for advanced melanoma.

Fixed-functional appliance treatment combined with growth hormone therapy.

PubMed

Jung, Min-Ho

2017-09-01

The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2006-01-01

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

Antihypertensive and anti-inflammatory actions of combined azilsartan and chlorthalidone in Dahl salt-sensitive rats on a high-fat, high-salt diet.

PubMed

Jin, Chunhua; O'Boyle, Sean; Kleven, Daniel T; Pollock, Jennifer S; Pollock, David M; White, John J

2014-08-01

Metabolic syndrome (MetS) and chronic kidney disease are global health issues. Metabolic syndrome induces hypertension and commonly results in renal damage. The optimal therapy for hypertension in MetS is unknown. Thiazide diuretics are first-line therapy; however, these drugs may have untoward effects. In the present study we investigated the effects of azilsartan (AZL), chlorthalidone (CLTD) and their combination on blood pressure and renal injury in a rodent model with features of MetS. Dahl salt-sensitive rats were fed high-fat (36% fat), high-salt (4% NaCl) diet. Groups were then treated with vehicle, AZL (3 mg/kg per day), CLTD (5 mg/kg per day) or AZL + CLTD. Mean arterial pressure was recorded continuously by telemetry. After 26 days, rats were killed humanely and their kidneys were harvested for histology. Both AZL and CLTD attenuated the rise in blood pressure compared with vehicle and the combination further reduced blood pressure compared with CLTD alone. All treatments reduced proteinuria and albuminuria. Nephrinuria was prevented only in groups treated with AZL. Nephrinuria was 57% lower and proteinuria was 47% lower with combination therapy compared with AZL alone. All treatments reduced the number of inflammatory cells in the kidney. In conclusion, in our model, AZL and CLTD lower blood pressure and exhibit renal protective effects. Treatment with AZL offers additional protection, as evidenced by lower nephrinuria and plasma monocyte chemoattractant protein-1 levels. Combination therapy afforded the greatest protective effects and may be the best choice for hypertensive therapy in MetS. © 2014 Wiley Publishing Asia Pty Ltd.

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study

PubMed Central

Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

Aim: We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. Methods: The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. Results: A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean ± SD changes in LDL cholesterol were −24.2% ± 14.7% with combination therapy, −16.0% ± 16.0% with fenofibrate alone, and −17.4% ± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p < 0.01 for each). The corresponding values for triglycerides were −40.0% ± 29.5%, −40.1% ± 28.7%, and −3.4% ± 32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. Conclusion: The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia. PMID:27397061

Efficacy and Safety of Long-term Coadministration of Fenofibrate and Ezetimibe in Patients with Combined Hyperlipidemia: Results of the EFECTL Study.

PubMed

Oikawa, Shinichi; Yamashita, Shizuya; Nakaya, Noriaki; Sasaki, Jun; Kono, Suminori

2017-01-01

We investigated the safety and efficacy of a long-term combination therapy with fenofibrate and ezetimibe in Japanese patients with combined hyperlipidemia, in comparison with fenofibrate or ezetimibe alone. The study was a three-arm parallel-group, open-label randomized trial. Eligible patients were assigned to a combination therapy with fenofibrate (200 mg/day in capsule form or 160 mg/day in tablet form) and ezetimibe (10 mg/day), the fenofibrate monotherapy, or the ezetimibe monotherapy, which lasted for 52 weeks. The changes in serum low-density lipoprotein (LDL) cholesterol and triglycerides were the primary outcomes. A total of 236 patients were assigned to one of the three treatments, and the number of patients included in the final analysis was 107 in the combination therapy, 52 in the fenofibrate monotherapy, and 51 in the ezetimibe monotherapy. Mean±SD changes in LDL cholesterol were -24.2%±14.7% with combination therapy, -16.0%±16.0% with fenofibrate alone, and -17.4%± 10.1% with ezetimibe alone. The combination therapy resulted in a significantly greater reduction in LDL cholesterol as compared with each monotherapy (p＜0.01 for each). The corresponding values for triglycerides were -40.0%±29.5%, -40.1%±28.7%, and -3.4%±32.6%, respectively. Fenofibrate use was associated with some changes in laboratory measurements, but there was no differential adverse effect between the combination therapy and fenofibrate monotherapy. The combination therapy with fenofibrate and ezetimibe substantially reduces concentrations of LDL cholesterol and triglycerides and is safe in a long-term treatment in Japanese patients with combined hyperlipidemia.

[The use of low-frequency magnetotherapy and EHF puncture in the combined treatment of arterial hypertension in vibration-induced disease].

PubMed

Drobyshev, V A; Filippova, G N; Loseva, M I; Shpagina, L A; Shelepova, N V; Zhelezniak, M S

2000-01-01

Combination of EHF therapy + magnetotherapy + drugs results in faster and persistent hypotensive and analgetic effect compared to standard drug therapy, potentiates action of vascular drugs on cerebral and peripheral circulation, reduces dose of hypotensive drugs in patients with arterial hypertension and vibration disease.

"Radiobiology of Proton Therapy": Results of an international expert workshop.

PubMed

Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg; Seidlitz, Annekatrin; Peitzsch, Claudia; Bentzen, Søren M; Bortfeld, Thomas; Debus, Jürgen; Deutsch, Eric; Langendijk, Johannes A; Loeffler, Jay S; Mohan, Radhe; Scholz, Michael; Sørensen, Brita S; Weber, Damien C; Baumann, Michael; Krause, Mechthild

2018-05-31

The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full advantage of the opportunities offered by proton radiation for clinical radiotherapy requires a better understanding of the radiobiological effects of protons alone or combined with drugs or immunotherapy on normal tissues and tumors. This report summarizes the main results of the international expert workshop "Radiobiology of Proton Therapy" that was held in November 2016 in Dresden. It addresses the major topics (1) relative biological effectiveness (RBE) in proton beam therapy, (2) interaction of proton radiobiology with radiation physics in current treatment planning, (3) biological effects in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data repositories will be most important to achieve this goal. Copyright © 2018 Elsevier B.V. All rights reserved.

[The application of combined physiotherapeutic methods for the complex treatment of patients with dyscirculatory encephalopathy].

PubMed

Shiman, A G; Klocheva, E G; Kaiumov, S F; Shoferova, S D; Zhukova, M V

2012-01-01

This article reports the results of applying basic pharmacotherapy (enalapril, cytoflavin) and its combination with physical factors (transcranial electrostimulation, combined application oftranscranial electrostimulation and low-frequency magnetic therapy) in the complex treatment of patients with stage I-II dyscirculatory encephalopathy. The study has demonstrated that the combined treatment with cytoflavin, enalapril, transcranial electrostimulation and low-frequency magnetic therapy produced the most pronounced therapeutic effect (82.5%), as confirmed by positive dynamics of clinical and functional parameters.

Group Cognitive Therapy and Alprazolam in the Treatment of Depression in Older Adults.

ERIC Educational Resources Information Center

Beutler, Larry E.; And Others

1987-01-01

Explored relative and combined effectiveness of alprazolam and group cognitive therapy among 56 elderly adults experiencing major affective disorder. Results revealed that individuals assigned to group cognitive therapy showed consistent improvement in subjective state and sleep efficiency relative to non-group-therapy subjects. No differences…

Investigating the Effects of Sweat Therapy on Group Dynamics and Affect

ERIC Educational Resources Information Center

Colmant, Stephen A.; Eason, Evan A.; Winterowd, Carrie L.; Jacobs, Sue C.; Cashel, Chris

2005-01-01

In this study, we examined the effects of sweat therapy on group dynamics and affect. Sweat therapy is the combination of intense heat exposure with psychotherapy or counseling (Colmant & Merta, 1999; 2000). Twenty-four undergraduates were separated by sex and randomly assigned to eight sessions of either a sweat or non-sweat group counseling…

Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer.

PubMed

Ribas, Ricardo; Pancholi, Sunil; Rani, Aradhana; Schuster, Eugene; Guest, Stephanie K; Nikitorowicz-Buniak, Joanna; Simigdala, Nikiana; Thornhill, Allan; Avogadri-Connors, Francesca; Cutler, Richard E; Lalani, Alshad S; Dowsett, Mitch; Johnston, Stephen R; Martin, Lesley-Ann

2018-06-08

Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER + ) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility. A panel of ER + BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1 wt or ESR1 Y537S , modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies. Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001. Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER.

Does electrical stimulation reduce spasticity after stroke? A randomized controlled study.

PubMed

Bakhtiary, Amir H; Fatemy, Elham

2008-05-01

To investigate the therapeutic effect of electrical stimulation on plantarflexor spasticity in stroke patients. A randomized controlled clinical trial study. Rehabilitation clinic of Semnan University of Medical Sciences. Forty stroke patients (aged from 42 to 65 years) with ankle plantarflexor spasticity. Fifteen minutes of inhibitory Bobath techniques were applied to one experimental group and a combination of 9 minutes of electrical stimulation on the dorsiflexor muscles and inhibitory Bobath techniques was applied to another group for 20 sessions daily. Passive ankle joint dorsiflexion range of motion, dorsiflexion strength test, plantarflexor muscle tone by Modified Ashworth Scale and soleus muscle H-reflex. The mean change of passive ankle joint dorsiflexion in the combination therapy group was 11.4 (SD 4.79) degrees versus 6.1 (SD 3.09) degrees, which was significantly higher (P = 0.001). The mean change of plantarflexor muscle tonicity measured by the Modified Ashworth Scale in the combination therapy group was -1.6 (SD 0.5) versus -1.1 (SD 0.31) in the Bobath group (P = 0.001). Dorsiflexor muscle strength was also increased significantly (P = 0.04) in the combination therapy group (0.7 +/- 0.37) compared with the Bobath group (0.4 +/- 0.23). However, no significant change in the amplitude of H-reflex was found between combination therapy (-0.41 +/- 0.29) and Bobath (-0.3 +/- 0.28) groups. Therapy combining Bobath inhibitory technique and electrical stimulation may help to reduce spasticity effectively in stroke patients.

[The assessment of the effectiveness of fenspiride (erespal) for the combined treatment of the patients presenting with exudative otitis media].

PubMed

Mel'chinskiĭ, A N; Vasilenko, D Iu; Kiseleva, G V

2013-01-01

The objective of the present work was to estimate the effectiveness and safety of combined anti-inflammatory therapy of exudative otitis media with the use of fenspiride (erespal). The study included 75 patients of whom 35 (group 1) were given standard therapy supplemented by erespal (80 mg thrice daily); the remaining patients receiving standard therapy alone formed group 2 (control). The patients treated with erespal reported the subjective improvement of hearing and reduced congestion on days 7 - 8. Similar changes in group 2 occurred on day 10. It is concluded that the use of erespal for the combined treatment of the patients presenting with exudative otitis media reduces the duration of hospital stay, accelerates recovery, and promotes rapid normalization of hearing.

Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

PubMed

Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

2011-02-01

Triamcinolone acetonide (TA) is one of the first pharmacologic compounds evaluated for the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The most important effects of TA consist in the stabilisation of the blood-retinal barrier and the down-regulation of inflammation. TA also has anti-angiogenic and anti-fibrotic properties. The peculiar characteristic of being well tolerated by ocular tissues and the capability to remain active for many months after a single intravitreal injection, make this drug a safe and effective alternative. In the past decade, intravitreal injection of TA (IVTA) has emerged as a useful treatment of several ocular diseases such as uveitis, macular edema secondary to retinal vasculature disease, neovascularisation and vitreoretinopathy. In this paper, we review all the available evidence of its use in AMD as mono-therapy or in combination with other treatments, and we discuss which role TA will play in the treatment of AMD in the future. The first experiences with IVTA as monotherapy for the treatment of exudative AMD reported a positive outcome in transiently reducing the leakage from CNV. However, in the long-term follow-up, IVTA as monotherapy had no effect on the risk of severe visual acuity loss, despite a significant anti-angiogenic effect found 3 months after the treatment. Consequently, studies using the combination of IVTA and photodynamic therapy (PDT), which acts synergistically, were performed. They reported to improve vision and to reduce the number of re-treatments with PDT. A large number of publications confirmed the positive synergic role of combining TA and PDT (therapies) for the treatment of all types of CNV: classic or predominantly classic, occult or minimally classic and RAP (Retinal Angiomatous Proliferation) lesions. The advantages registered with the use of IVTA plus PDT compared to PDT alone were partially limited by the side effects, such as the rapid evolution of cataract. Nevertheless, cataract surgery may stimulate the development of CNV (result in stimulating CNV). However, in large, randomized, clinical trials on combination therapy of TA and PDT, visual acuity failed to show an improvement, even though the lesion size and subretinal fluid had decreased, compared to controls treated with PDT alone. Some authors reported an increased risk of developing macular atrophy after the combination therapy with IVTA and PDT. Reduction of the PDT fluence rate in association with the use of steroids resulted in reducing the risk of macular atrophy and in a better visual acuity outcome. The introduction of anti-VEGF-based drugs has revolutionized the treatment of AMD and has replaced all the previous therapies used for CNV. Visual improvement becomes an expectation in a higher proportion of patients, previously limited to minimizing vision loss. Anti-VEGF therapy also resulted in superior visual improvement compared to all types of combination therapy with IVT and PDT. Nevertheless, anti-VEGF monotherapy also has many limitations due to the need of repetitive treatments, increased costs and tachyphylaxis. Treatment regimens involving TA in combination therapy with anti-VEGF and PDT may preserve benefits for substantially longer periods. A question remains open on whether a combination treatment with anti-VEGF, triamcinolone and/or PDT may be a treatment option in patients with exudative AMD, by offering, with one cycle of therapy, functional VA benefits comparable to those observed with continued monthly anti-VEGF therapy. Further trials, of higher scientific significance, are needed to study the potential of these treatment options.

Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

PubMed

Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

2017-12-01

Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

Combination of butylphthalide with umbilical mesenchymal stem cells for the treatment of delayed encephalopathy after carbon monoxide poisoning.

PubMed

Wang, Huanjun; Li, Yan; Wu, Qiang; Xu, Chenglong; Liu, Qingran

2016-12-01

Delayed encephalopathy after carbon monoxide (CO) poisoning (DEACMP) is still a clinical challenge. This study aimed to investigate the efficacy of combined therapy of mesenchymal stem cell (MSC) transplantation and butylphthalide in DEACMP patients.Forty-two DEACMP patients were treated with 1 of the 3 therapies: combined therapy of MSC transplantation and butylphthalide; MSC transplantation alone; or hyperbaric oxygen therapy. The MSCs were alternatively injected into the subarachnoid space and the carotid artery using a self-made high-pressure injector. The Mini-Mental State Examination and the Barthel index of activities of daily living were administered before the treatment, and at 1 month, 3 months, and 6 months after the treatment. Computed tomography and magnetic resonance imaging results before and after the treatment were compared.At 1 month, 3 months, and 6 months after the treatment, the Mini-Mental State Examination scores and the Barthl scores were significantly higher in patients with the combined therapy of MSC transplantation and butylphthalide than those in patients with MSC transplantation alone or hyperbaric oxygen therapy (all P < 0.0001). No significant adverse events occurred.The combination of MSC transplantation and butylphthalide is safe and effective in treating DEACMP.

Effects of atomoxetine with and without behavior therapy on the school and home functioning of children with attention-deficit/hyperactivity disorder.

PubMed

Waxmonsky, James G; Waschbusch, Daniel A; Pelham, William E; Draganac-Cardona, Lillian; Rotella, Bryan; Ryan, Lynn

2010-11-01

To evaluate the effects of atomoxetine alone and in combination with behavior therapy on the school functioning of children with attention-deficit/hyperactivity disorder (ADHD). Most atomoxetine studies have not assessed school functioning other than by measuring the change in ADHD symptoms. Combining behavior therapy with atomoxetine may be particularly beneficial for the academic domain as medication has not been found to produce sustained benefits in this realm. However, there is little research examining the effects of combining atomoxetine and behavior therapy. In an 8-week open-label trial, 56 children aged 6-12 years with ADHD diagnosed according to DSM-IV-TR were randomly assigned to receive atomoxetine and behavior therapy or atomoxetine alone. Behavior therapy consisted of an 8-week parenting course, a child social skills course, and a teacher-implemented daily report card of classroom behavior. The primary outcome was direct observation of the subject's classroom behavior. Secondary outcomes included change in ADHD symptoms and functioning at home and school. All data were collected between March 2007 and May 2008. Classroom observations showed that atomoxetine decreased rule violations (P < .0001). Moreover, atomoxetine was associated with significant improvements in ADHD and oppositional defiant disorder symptoms at home and school and enhanced functioning in both domains (Impairment Rating Scale: all P < .001). Combined treatment led to greater improvements in parent-rated symptoms of inattention (P < .01), problem behaviors (P < .001), and academic impairment (P < .05). However, teachers did not report significant group differences. Atomoxetine improved ADHD symptoms and classroom functioning as measured by parents, teachers, and direct observation. The addition of behavior therapy led to further improvements at home but not at school. clinicaltrials.gov Identifier: NCT00918567. © Copyright 2010 Physicians Postgraduate Press, Inc.

Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

PubMed

Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

2015-12-16

Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Effects of inhibitory activity on mycelial growth of Candida albicans and therapy for murine oral candidiasis by the combined use of terpinen-4-ol and a middle-chain fatty acid, capric acid].

PubMed

Ninomiya, Kentaro; Hayama, Kazumi; Ishijima, Sanae; Takahashi, Miki; Kurihara, Junichi; Abe, Shigeru

2013-01-01

The combined effect of terpinen-4-ol, the main component of tea tree oil, and capric acid against mycelial growth of Candida albicans and murine oral candidiasis was evaluated in vitro and in vivo. Mycelial growth of C. albicans was estimated by the Cristal violet method. Combination of these compounds revealed a potent synergistic inhibition of growth. Therapeutic efficacy of the combination was evaluated microbiologically in murine oral candidiasis, and its application of the compounds clearly demonstrated therapeutic activity. Based on these results, the combined agent of terpinen-4-ol and capric acid was discussed as a possible candidate for oral candidiasis therapy.

Combination Therapy with Atorvastatin and Amlodipine Suppresses Angiotensin II-Induced Aortic Aneurysm Formation

PubMed Central

Takahashi, Kikuyo; Matsumoto, Yasuharu; Do.e, Zhulanqiqige; Kanazawa, Masanori; Satoh, Kimio; Shimizu, Takuya; Sato, Akira; Fukumoto, Yoshihiro; Shimokawa, Hiroaki

2013-01-01

Background Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease. It is controversial whether statin and calcium channel blockers (CCBs) has an inhibitory effect on the expansion of AAA. Some studies reported that CCBs have an inhibitory effect on Rho-kinase activity. Rho-kinase plays an important role in the pathogenesis of various cardiovascular diseases. However, there is no study reporting of the association between Rho-kinase and human AAAs. Methods and Results Experimental AAA was induced in Apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II (AngII) for 28 days. They were randomly divided into the following 5 groups; saline infusion alone (sham), AngII infusion alone, AngII infusion plus atorvastatin (10 mg/kg/day), AngII infusion plus amlodipine (1 mg/kg/day), and AngII infusion plus combination therapy with atorvastatin (10 mg/kg/day) and amlodipine (1 mg/kg/day). The combination therapy significantly suppressed AngII-induced increase in maximal aortic diameter as compared with sham, whereas each monotherapy had no inhibitory effects. The combination therapy significantly reduced AngII-induced apoptosis and elastin degradation at the AAA lesion, whereas each monotherapy did not. Moreover, Rho-kinase activity, as evaluated by the extent of phosphorylation of myosin-binding subunit (a substrate of Rho-kinase) and matrix metalloproteinase activity were significantly increased in the AngII-induced AAA lesion as compared with sham, both of which were again significantly suppressed by the combination therapy. In human aortic samples, immunohistochemistory revealed that the activity and expression of Rho-kinase was up-regulated in AAA lesion as compared with abdominal aorta from control subjects. Conclusions Rho-kinase is up-regulated in the aortic wall of human AAA. The combination therapy with amlodipine and Atorvastatin, but not each monotherapy, suppresses AngII-induced AAA formation in mice in vivo, for which Rho-kinase inhibition may be involved. PMID:23967318

Pullulan-coated phospholipid and Pluronic F68 complex nanoparticles for carrying IR780 and paclitaxel to treat hepatocellular carcinoma by combining photothermal therapy/photodynamic therapy and chemotherapy

PubMed Central

Zhang, Tao; Wan, Guoyun; Chen, Bowei; Xiong, Qingqing; Zhang, Jie; Zhang, Wenxue; Wang, Yinsong

2017-01-01

IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy. PMID:29255359

Pullulan-coated phospholipid and Pluronic F68 complex nanoparticles for carrying IR780 and paclitaxel to treat hepatocellular carcinoma by combining photothermal therapy/photodynamic therapy and chemotherapy.

PubMed

Wang, Dan; Zhang, Sipei; Zhang, Tao; Wan, Guoyun; Chen, Bowei; Xiong, Qingqing; Zhang, Jie; Zhang, Wenxue; Wang, Yinsong

2017-01-01

IR780, a near-infrared dye, can also be used as a photosensitizer both for photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, we designed a simple but effective nanoparticle system for carrying IR780 and paclitaxel, thus hoping to combine PTT/PDT and chemotherapy to treat hepatocellular carcinoma (HCC). This nanosystem, named PDF nanoparticles, consisted of phospholipid/Pluronic F68 complex nanocores and pullulan shells. IR780 and paclitaxel were loaded separately into PDF nanoparticles to form PDFI and PDFP nanoparticles, which had regular sphere shapes and relatively small sizes. Upon near-infrared laser irradiation at 808 nm, PDFI nanoparticles showed strong PTT/PDT efficacy both in vitro and in vivo. In MHCC-97H cells, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles exhibited significant synergistic effects on inhibiting cell proliferation and inducing cell apoptosis and cell cycle arrest at G2/M phase. In MHCC-97H tumor-bearing mice, PDFI nanoparticles exhibited excellent HCC-targeting and accumulating capability after intravenous injection. Furthermore, the combined treatment of PDFI nanoparticles/laser irradiation and PDFP nanoparticles also effectively inhibited the tumor growth and the tumor angiogenesis in MHCC-97H tumor-bearing mice. In summary, we put forward a therapeutic strategy for HCC treatment by combining PTT/PDT and chemotherapy.

Ciclosporin use in multi-drug therapy for meningoencephalomyelitis of unknown aetiology in dogs.

PubMed

Adamo, P F; Rylander, H; Adams, W M

2007-09-01

To evaluate the efficacy and safety of ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole in dogs with diagnosis of meningoencephalomyelitis of unknown aetiology. Medical records of 10 dogs diagnosed with meningoencephalomyelitis of unknown aetiology and treated with ciclosporin therapy alone or in combination with corticosteroids and/or ketoconazole were reviewed at the Veterinary Medical Teaching Hospital, University of Wisconsin-Madison. Laboratory abnormalities, side effects, clinical and cerebrospinal fluid responses to treatment and association between blood ciclosporin level and response to treatment were evaluated. Histopathological diagnosis was available in three patients. No significant abnormalities were detected on serial complete blood count and serum chemistry panel in any of the dogs. Side effects of ciclosporin therapy included excessive shedding, gingival hyperplasia and hypertrichosis. Overall median survival time for all dogs in the study was 930 days (range, 60 to more than 1290 days). In all dogs, serial cerebrospinal fluid analysis showed a marked improvement in the inflammation. Results suggest that ciclosporin either alone or in combination with ketoconazole may be a safe and effective treatment for meningoencephalomyelitis of unknown aetiology in dogs.

Should anti-inhibitor coagulant complex and tranexamic acid be used concomitantly?

PubMed

Valentino, L A; Holme, P A

2015-11-01

Inhibitor development in haemophilia patients is challenging especially when undergoing surgical procedures. The development of an inhibitor precludes using factor VIII (FVIII) therapy thereby requiring a bypassing agent (BPA) for surgical bleeding prophylaxis if the FVIII inhibitor titre >5 BU. Concomitant use of anti-inhibitor coagulant complex (AICC) and tranexamic acid has been reported in the literature as a beneficial treatment for this population. Anti-inhibitor coagulant complex is known to cause an increase in thrombin generation and tranexamic acid inhibits fibrinolysis. Hence, the combined used of AICC and tranexamic acid has been limited due to safety concerns over possibilities of increased risk of thrombotic events and disseminated intravascular coagulation. However, the rationale for concomitant therapy is to obtain a potential synergistic effect and to increase clot stability. We conducted a literature review of past studies and individual case reports of concomitant use of AICC and tranexamic acid, which was extensively used during dental procedures. Evidence also exists for concomitant use of the combined therapy in orthopaedic procedures, control of gastrointestinal bleeding, epistaxis and cerebral haemorrhages. Some patients who received the combined therapy had failed monotherapy with a single BPA prior to combined therapy. There were no reports of thrombotic complications related to the concomitant therapy and haemostasis was achieved in all cases. Anti-inhibitor coagulant complex and tranexamic acid therapy was found to be safe, well-tolerated and effective therapy in haemophilia patients with inhibitors. Additional randomized controlled studies should be performed to confirm these findings. © 2015 John Wiley & Sons Ltd.

Effects of Aquatic Therapy and Land-Based Therapy versus Land-Based Therapy Alone on Range of Motion, Edema, and Function after Hip or Knee Replacement: A Systematic Review and Meta-analysis.

PubMed

Gibson, Alison J; Shields, Nora

2015-01-01

To determine whether aquatic therapy in combination with land-based therapy improves patient outcomes after hip or knee arthroplasty compared with land-based therapy alone. For this systematic review, six online databases (MEDLINE, CINAHL, AMED, EMBASE, Cochrane, and PEDro) were searched from the earliest date available until September 2013. Controlled trials published in English in a peer-reviewed journal that compared aquatic therapy in combination with land-based therapy with land-based therapy alone were included; trial quality was assessed using the PEDro scale. Data were presented as standardized mean differences (SMDs), their associated 95% CIs, and meta-analyses. Three small trials of moderate quality were included in the qualitative analysis. Meta-analysis of two of these studies found moderate-quality evidence that aquatic therapy in combination with land-based therapy improves functional outcomes (SMD=0.53; 95% CI, 0.03-1.03), knee range of motion (measured in knee or hip arthroplasty; SMD=0.78; 95% CI, 0.27-1.29), and edema (SMD=-0.66; 95% CI, -1.16 to -0.15) compared with land-based therapy alone. The results for improved functional outcomes were not considered clinically significant. It is not possible to draw confident conclusions from this review because of the small number of studies of limited quality and the modest differences found. Further studies of sound methodological quality are required to confirm the results. Economic analysis alongside randomized controlled trials is needed to examine the cost-effectiveness of these clinical outcomes.

Mirror therapy combined with biofeedback functional electrical stimulation for motor recovery of upper extremities after stroke: a pilot randomized controlled trial.

PubMed

Kim, Jung Hee; Lee, Byoung-Hee

2015-06-01

The objective of this study was to evaluate the effects of mirror therapy in combination with biofeedback functional electrical stimulation (BF-FES) on motor recovery of the upper extremities after stroke. Twenty-nine patients who suffered a stroke > 6 months prior participated in this study and were randomly allocated to three groups. The BF-FES + mirror therapy and FES + mirror therapy groups practiced training for 5 × 30 min sessions over a 4-week period. The control group received a conventional physical therapy program. The following clinical tools were used to assess motor recovery of the upper extremities: electrical muscle tester, electrogoniometer, dual-inclinometer, electrodynamometer, the Box and Block Test (BBT) and Jabsen Taylor Hand Function Test (JHFT), the Functional Independence Measure, the Modified Ashworth Scale, and the Stroke Specific Quality of Life (SSQOL) assessment. The BF-FES + mirror therapy group showed significant improvement in wrist extension as revealed by the Manual Muscle Test and Range of Motion (p < 0.05). The BF-FES + mirror therapy group showed significant improvement in the BBT, JTHT, and SSQOL compared with the FES + mirror therapy group and control group (p < 0.05). We found that BF-FES + mirror therapy induced motor recovery and improved quality of life. These results suggest that mirror therapy, in combination with BF-FES, is feasible and effective for motor recovery of the upper extremities after stroke. Copyright © 2014 John Wiley & Sons, Ltd.

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

PubMed

Rahme, Christine; Butterfield, Jill M; Nicasio, Anthony M; Lodise, Thomas P

2014-12-01

We are rapidly approaching a crisis in antibiotic resistance, particularly among Gram-negative pathogens. This, coupled with the slow development of novel antimicrobial agents, underscores the exigency of redeploying existing antimicrobial agents in innovative ways. One therapeutic approach that was heavily studied in the 1980s but abandoned over time is dual beta-lactam therapy. This article reviews the evidence for combination beta-lactam therapy. Overall, in vitro, animal and clinical data are positive and suggest that beta-lactam combinations produce a synergistic effect against Gram-negative pathogens that rivals that of beta-lactam-aminoglycoside or beta-lactam-fluoroquinolone combination therapy. Although the precise mechanism of improved activity is not completely understood, it is likely attributable to an enhanced affinity to the diverse penicillin-binding proteins found among Gram negatives. The collective data indicate that dual beta-lactam therapy should be revisited for serious Gram-negative infections, especially in light of the near availability of potent beta-lactamase inhibitors, which neutralize the effect of problematic beta-lactamases. Copyright © 2014 Elsevier Inc. All rights reserved.

Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

PubMed

Glaser, Rebecca L; Dimitrakakis, Constantine

2014-06-01

Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin.

PubMed

Suii, Hirokazu; Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was -3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only -1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV.

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin

PubMed Central

Ozeki, Itaru; Tatsumi, Ryoji; Yamaguchi, Masakatsu; Kimura, Mutsuumi; Arakawa, Tomohiro; Nakajima, Tomoaki; Kuwata, Yasuaki; Ohmura, Takumi; Hige, Shuhei; Karino, Yoshiyasu; Toyota, Joji

2017-01-01

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was −3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only −1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV. PMID:29375917

The Effect of Entonox, Play Therapy and a Combination on Pain Relief in Children: A Randomized Controlled Trial.

PubMed

Mohan, Simi; Nayak, Ruma; Thomas, Reju Joseph; Ravindran, Vinitha

2015-12-01

Pediatric pain is often undertreated/neglected due to time constraints, difficulties in timing of oral analgesics, fear of side effects of opioids and anxiolytics, and apprehension of additional pain in the use of local anesthetic injections. In this study, the researcher was prompted to choose rapidly acting interventions that were low dose and allowed the child to stay alert, suitable for a quick discharge. The purpose of this study was to evaluate the effects of Entonox, play therapy, and a combination to relieve procedural pain in children aged 4-15 years. The study was designed as a randomized controlled trial; the subjects were divided into four groups using a sequential allocation plan from 123 total subjects. Group A received Entonox, Group B received play therapy, Group C received both Entonox and play therapy, and Group D received existing standard interventions. The study was vetted by the departmental study review committee. The pain level was assessed using FLACC scale for children aged 4-9 years and the Wong Bakers Faces Pain Scale for children aged 10-15 years; scores ranged from 0 to 10. All the data were analyzed using SPSS 16.0 with descriptive statistics and, inferential statistics. The mean pain scores were as follows: Entonox group, 2.87; Play therapy group, 4; combination group, 3; and control group, 5.87. When statistical testing was applied, a significant reduction in the pain score in all the three experimental groups when compared to the control group was found (p = .002), but not in the pain score among the three experimental groups (p = .350). The findings of this study indicated that all three interventions were effective in lowering pain scores when compared to the control group. Play therapy is as potent as Entonox in relieving procedural pain, though there was no additive effect on pain relief when play therapy and Entonox were combined. A protocol for age-related choice between play therapy and Entonox administration was introduced as a standing order in the Pediatric Surgery department for acute procedural pain relief. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

[A case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy].

PubMed

Ami, Katsunori; Seki, Ryouta; Takasaki, Jun; Amagasa, Hidetoshi; Kamikozuru, Hirotaka; Ganno, Hideaki; Kurokawa, Toshiaki; Fukuda, Akira; Nagahama, Takeshi; Ando, Masayuki; Yamada, Yosuke; Kodaka, Fumi; Arai, Kuniyoshi

2012-11-01

At present, fluorouracil and cisplatin combination therapy is the standard chemotherapy against esophageal cancer, but the choice of second-line chemotherapy is controversial. Furthermore, the effect of radiation therapy against lung metastasis from esophageal cancer is unclear. We report a case of lung metastasis from esophageal cancer resistant to fluorouracil and cisplatin combination therapy but responsive to radiation therapy. The patient was a 55-year-old woman who had undergone an operation for esophageal cancer at another hospital. A single right lung metastasis appeared 1 year after the operation. Combined fluorouracil and cisplatin therapy was administrated for 5 courses, but the lung metastasis increased in size. Afterwards, she was admitted to our hospital. We treated her with 14 courses of S-1 and docetaxel combination therapy administered over 13 months. The lung metastasis was decreased for a period. Furthermore, radiofrequency ablation under computed tomography was performed against the lung metastasis re-growth at another hospital. Although the lung metastasis increased in size, no further metastases were detected during the clinical course. The patient was treated with radiotherapy for the lung metastasis re-growth. The tumor had almost disappeared by 10 months after the completion of radiotherapy. Currently, she is receiving palliative care as an outpatient and the lung metastasis has not been evident for 2 years since the completion of radiotherapy.

Antimicrobial photodynamic therapy combined with conventional endodontic treatment to eliminate root canal biofilm infection.

PubMed

Garcez, Aguinaldo S; Ribeiro, Martha S; Tegos, George P; Núñez, Silvia C; Jorge, Antonio O C; Hamblin, Michael R

2007-01-01

To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-micro fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. (c) 2006 Wiley-Liss, Inc.

A Chaperone Enhances Blood α-Glucosidase Activity in Pompe Disease Patients Treated With Enzyme Replacement Therapy

PubMed Central

Parenti, Giancarlo; Fecarotta, Simona; la Marca, Giancarlo; Rossi, Barbara; Ascione, Serena; Donati, Maria Alice; Morandi, Lucia Ovidia; Ravaglia, Sabrina; Pichiecchio, Anna; Ombrone, Daniela; Sacchini, Michele; Pasanisi, Maria Barbara; De Filippi, Paola; Danesino, Cesare; Della Casa, Roberto; Romano, Alfonso; Mollica, Carmine; Rosa, Margherita; Agovino, Teresa; Nusco, Edoardo; Porto, Caterina; Andria, Generoso

2014-01-01

Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone. PMID:25052852

Clinical efficiency of applying low-intensity laser therapy in treating dyscirculatory encephalopathy

NASA Astrophysics Data System (ADS)

Putilina, M. V.; Kozlov, V. I.; Vakhtin, V. I.

2001-04-01

An investigation was made of applying laser therapy combined with drug preparations in treating 300 patients affected by dyscirculatory encephalopathy. Neurological and neuropsychological examinations together with electroencephalography, rheoencephalography, computerized tomography, and magnetic resonance imaging were used to assess the patients' states prior to and after the treatment. It was found that the combined application of laser therapy and drug preparations produced a more pronounced therapeutic effect as compared with that produced by the separate application of laser therapy and drug preparations. The results obtained allowed us to conclude that the 0.89 micrometers laser infrared radiation increased patients' susceptibility to drugs. Moreover, the combined laser therapy improved the cerebral bloodflow and activated the metabolic and plastic functions of neurons. This decreased or eliminated late complications provoked by the cerebral blood circulation insufficiency.

Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma

PubMed Central

Hu-Lieskovan, Siwen; Mok, Stephen; Moreno, Blanca Homet; Tsoi, Jennifer; Faja, Lidia Robert; Goedert, Lucas; Pinheiro, Elaine M.; Koya, Richard C.; Graeber, Thomas; Comin-Anduix, Begoña; Ribas, Antoni

2016-01-01

Combining immunotherapy and BRAF targeted therapy may result in improved antitumor activity with the high response rates of targeted therapy and the durability of responses with immunotherapy. However, the first clinical trial testing the combination of the BRAF inhibitor vemurafenib and the CTLA-4 antibody ipilimumab was terminated early due to substantial liver toxicities. MEK inhibitors can potentiate the MAPK inhibition in BRAF mutant cells, while potentially alleviating the unwanted paradoxical MAPK activation in BRAF wild type cells that lead to side effects when using BRAF inhibitors alone. However, there is the concern of MEK inhibitors being detrimental to T cell functionality. Using a mouse model of syngeneic BRAFV600E driven melanoma, we tested whether addition of the MEK inhibitor trametinib would enhance the antitumor activity of combined immunotherapy with the BRAF inhibitor dabrafenib. Combination of dabrafenib and trametinib with pmel-1 adoptive cell transfer (ACT) showed complete tumor regression, increased T cell infiltration into tumors and improved in vivo cytotoxicity. Single agent dabrafenib increased tumor-associated macrophages and T regulatory cells (Tregs) in tumors, which decreased with the addition of trametinib. The triple combination therapy resulted in increased melanosomal antigen and MHC expression, and global immune-related gene up-regulation. Given the up-regulation of PD-L1 seen with dabrafenib and/or trametinib combined with antigen-specific ACT, we tested combination of dabrafenib, trametinib with anti-PD1 therapy in SM1 tumors, and observed superior anti-tumor effect. Our findings support the testing of triple combination therapy of BRAF and MEK inhibitors with immunotherapy in patients with BRAFV600E mutant metastatic melanoma. PMID:25787767

Watchful waiting with periodic liver biopsy versus immediate empirical therapy for histologically mild chronic hepatitis C. A cost-effectiveness analysis.

PubMed

Wong, J B; Koff, R S

2000-11-07

Not all patients with histologically mild chronic hepatitis C progress to cirrhosis. To compare no antiviral treatment, periodic liver biopsy with subsequent antiviral treatment for moderate hepatitis or cirrhosis, and immediate antiviral therapy. Cost-effectiveness analysis. Clinical trial data and published studies. Hepatitis C virus-infected patients with histologically mild hepatitis. Lifetime. Societal. Immediate combination antiviral treatment or biopsy every 3 years plus combination antiviral therapy for moderate hepatitis or cirrhosis. Life expectancy, quality-adjusted life expectancy, and costs. Over 20 years, biopsy every 3 years with treatment of moderate hepatitis would avoid treatment in 50% of the cohort and would result in an 18% likelihood of cirrhosis compared with 16% for immediate treatment and 27% for no antiviral therapy. Immediate antiviral treatment should increase life expectancy by 1.0 quality-adjusted life-year compared with biopsy management. Over an average lifetime, biopsy management would lead to six liver biopsies costing $6200; immediate antiviral treatment would cost $5100 less than biopsy management because of savings related to biopsy and prevention of future hepatitis C-related morbidity. Immediate therapy was cost-effective compared with biopsy management and had a cost-effectiveness ratio of $7000 compared with no antiviral therapy. When age, sex, genotype, and estimates of histologic progression or compliance with follow-up are varied, immediate therapy should result in an increase of at least 0. 8 quality-adjusted life-year compared with biopsy management. For histologically mild chronic hepatitis C, initial combination treatment compared with periodic liver biopsy should reduce the future risk for cirrhosis, prolong life, and be cost-effective.

Treatment of murine invasive candidiasis with amphotericin B and cilofungin: evidence for enhanced activity with combination therapy.

PubMed Central

Sugar, A M; Goldani, L Z; Picard, M

1991-01-01

The in vivo interactions of cilofungin, an echinocandin antifungal agent, and amphotericin B, a polyene derivative, in a murine model of disseminated candidiasis have been investigated. While single therapy with either drug alone prolonged survival of infected mice, kidney colony counts were not appreciably reduced. In contrast, combination therapy, especially at higher doses of both drugs, resulted in significant prolongation of survival and suppression of growth of yeast cells in the kidneys. Combination therapy of experimental candidiasis with cilofungin and amphotericin B did not result in antagonism; rather, additive or synergistic effects were seen. Future preclinical work with other echinocandin and polyene derivatives should include studies evaluating the in vivo interactions of both classes of compounds. PMID:1759836

Neutron therapy of resistant thyroid gland cancer

NASA Astrophysics Data System (ADS)

Choynzonov, E. L.; Gribova, O. V.; Startseva, Zh. A.; Lisin, V. A.; Novikov, V. A.; Musabaeva, L. I.

2017-09-01

The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons c. The study included 45 patients with thyroid gland cancers who received the combined modality treatment and radiation therapy alone with the use of 6.3 MeV fast neutrons generated within U-120 cyclotron. The clinical trial of neutron-photon therapy used alone and in combination with the surgery for the patients with aggressive forms of thyroid cancer showed feasibility of increasing the effectiveness of treatment due to the reduction in the incidence of local recurrences. In addition, satisfactory treatment tolerance and absence of severe specific complications dictate the necessity of prospective studies to improve treatment outcomes.

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Combined concurrent nanoshell loaded macrophage-mediated photothermal and photodynamic therapies

NASA Astrophysics Data System (ADS)

Hirschberg, Henry; Trinidad, Anthony; Christie, Catherine E.; Peng, Qian; Kwon, Young J.; Madsen, Steen

2015-02-01

Macrophages loaded with gold nanoshells (AuNS), that convert near infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on head and neck squamous cell carcinoma (HNSCC). The results provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.

[Memantine as add-on medication to acetylcholinesterase inhibitor therapy for Alzheimer dementia].

PubMed

Haussmann, R; Donix, M

2017-01-01

Currently available data indicate superior therapeutic effects of combination treatment for Alzheimer dementia with memantine and acetylcholine esterase inhibitors in certain clinical contexts. Out of five randomized, placebo-controlled, double-blind trials two showed superior therapeutic effects in comparison to monotherapy with acetylcholinesterase inhibitors regarding various domains. Recently published meta-analyses and cost-benefit analyses also showed positive results. Recently published German guidelines for dementia treatment also take these new data into account and recommend combination treatment in patients with severe dementia on stable donepezil medication. This article gives an overview of current evidence for combination therapy.

[Chemotherapy in combination with laser coagulation or interstitial hyperthermia--effective combined therapy for disseminated skin melanoma].

PubMed

Akimov, M A; Gel'fond, M L; Gershanovich, M L; Barchuk, A S

2003-01-01

Thirty-eight patients with disseminated skin melanoma received chemotherapy in conjunction with laser coagulation or interstitial hyperthermia of intra- or subcutaneous metastases. Use of combination therapy was followed by a rise to 37% in total response and 16%--complete regression, respectively. Most effectiveness was attained when the dacarbazine + cisplatin + BCNU + tamoxifen regime was employed. In this group of 16 patients (46%), total response was 56% and, what is most significant, 31% in complete regression. In all cases of apparent response, polychemotherapy was administered both before and after laser coagulation or interstitial hyperthermia.

Combined enzyme/prodrug treatment by genetically engineered AT-MSC exerts synergy and inhibits growth of MDA-MB-231 induced lung metastases.

PubMed

Matuskova, Miroslava; Kozovska, Zuzana; Toro, Lenka; Durinikova, Erika; Tyciakova, Silvia; Cierna, Zuzana; Bohovic, Roman; Kucerova, Lucia

2015-04-09

Metastatic spread of tumor cells remains a serious problem in cancer treatment. Gene-directed enzyme/prodrug therapy mediated by tumor-homing genetically engineered mesenchymal stromal cells (MSC) represents a promising therapeutic modality for elimination of disseminated cells. Efficacy of gene-directed enzyme/prodrug therapy can be improved by combination of individual systems. We aimed to define the combination effect of two systems of gene therapy mediated by MSC, and evaluate the ability of systemically administered genetically engineered mesenchymal stromal cells to inhibit the growth of experimental metastases derived from human breast adenocarcinoma cells MDA-MB-231/EGFP. Human adipose tissue-derived mesenchymal stromal cells (AT-MSC) were retrovirally transduced with fusion yeast cytosine deaminase::uracil phosphoribosyltransferase (CD::UPRT) or with Herpes simplex virus thymidine kinase (HSVtk). Engineered MSC were cocultured with tumor cells in the presence of prodrugs 5-fluorocytosin (5-FC) and ganciclovir (GCV). Combination effect of these enzyme/prodrug approaches was calculated. SCID/bg mice bearing experimental lung metastases were treated with CD::UPRT-MSC, HSVtk-MSC or both in combination in the presence of respective prodrug(s). Treatment efficiency was evaluated by EGFP-positive cell detection by flow cytometry combined with real-time PCR quantification of human cells in mouse organs. Results were confirmed by histological and immunohistochemical examination. We demonstrated various extent of synergy depending on tested cell line and experimental setup. The strongest synergism was observed on breast cancer-derived cell line MDA-MB-231/EGFP. Systemic administration of CD::UPRT-MSC and HSVtk-MSC in combination with 5-FC and GCV inhibited growth of MDA-MB-231 induced lung metastases. Combined gene-directed enzyme/prodrug therapy mediated by MSC exerted synergic cytotoxic effect and resulted in high therapeutic efficacy in vivo.

Improved survival of mice bearing liver metastases of colon cancer cells treated with a combination of radioimmunotherapy and antiangiogenic therapy.

PubMed

Kinuya, Seigo; Yokoyama, Kunihiko; Koshida, Kiyoshi; Mori, Hirofumi; Shiba, Kazuhiro; Watanabe, Naoto; Shuke, Noriyuki; Bai, Jingming; Michigishi, Takatoshi; Tonami, Norihisa

2004-07-01

We attempted to determine whether the combined regimen of radioimmunotherapy (RIT) and antiangiogenic therapy would favorably affect the survival of animals bearing liver metastases of colon cancer cells. Daily antiangiogenic therapy with 2-methoxyestradiol (2-ME), 75 mg/kg, was initiated at 3 days following intrasplenic cell inoculation of LS180 colon cancer cells. RIT with 7 MBq of (131)I-A7, an IgG1 anti-colorectal monoclonal antibody, or (131)I-HPMS-1, an irrelevant IgG1, was conducted at 7 days. Production of vascular endothelial growth factor (VEGF) by LS180 cells was assessed in vitro. All nontreated mice died by 31 days following cell inoculation ( n=5). Monotherapy comprising 2-ME treatment resulted in slightly better survival of mice ( n=8) ( P<0.05). (131)I-A7 RIT displayed a marked therapeutic effect ( n=8) ( P<0.001); however, all animals eventually died due to metastases by 99 days. The combined regimen of (131)I-A7 RIT and antiangiogenic therapy demonstrated a superior therapeutic effect in comparison to monotherapy consisting of either RIT or antiangiogenic therapy ( n=10) ( P<0.05); three mice survived the entire 160-day observation period. The combination of antiangiogenic therapy and (131)I-HPMS-1 RIT failed to provide an appreciable benefit ( n=5). Treatment with 2-ME decreased VEGF production by LS180 cells in a dose-dependent fashion. In conclusion, a combination regimen comprising RIT and antiangiogenic therapy initiated at the early stage of metastasis would be of great benefit in terms of improvement of the therapeutic efficacy with respect to liver metastases.

Combined transcranial direct current stimulation and home-based occupational therapy for upper limb motor impairment following intracerebral hemorrhage: a double-blind randomized controlled trial.

PubMed

Mortensen, Jesper; Figlewski, Krystian; Andersen, Henning

2016-01-01

To investigate the combined effect of transcranial direct current stimulation (tDCS) and home-based occupational therapy on activities of daily living (ADL) and grip strength, in patients with upper limb motor impairment following intracerebral hemorrhage (ICH). A double-blind randomized controlled trial with one-week follow-up. Patients received five consecutive days of occupational therapy at home, combined with either anodal (n = 8) or sham (n = 7) tDCS. The primary outcome was ADL performance, which was assessed with the Jebsen-Taylor test (JTT). Both groups improved JTT over time (p < 0.01). The anodal group improved grip strength compared with the sham group from baseline to post-assessment (p = 0.025). However, this difference was attenuated at one-week follow-up. There was a non-significant tendency for greater improvement in JTT in the anodal group compared with the sham group, from baseline to post-assessment (p = 0.158). Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is a promising add-on intervention regarding training of upper limb motor impairment. It is well tolerated by patients and can easily be applied for home-based training. Larger studies with long-term follow-up are needed to further explore possible effects of tDCS in patients with ICH. Five consecutive days of tDCS combined with occupational therapy provided greater improvements in grip strength compared with occupational therapy alone. tDCS is well tolerated by patients and can easily be applied for home-based rehabilitation.

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study.

PubMed

Yang, Rui-Qi; Mao, Hua; Huang, Li-Yun; Su, Pei-Zhu; Lu, Min

2017-02-21

To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group ( P < 0.05). There were significant differences ( P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group ( P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group ( P < 0.05). Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa.

Comparison microbial killing efficacy between sonodynamic therapy and photodynamic therapy

NASA Astrophysics Data System (ADS)

Drantantiyas, Nike Dwi Grevika; Astuti, Suryani Dyah; Nasution, Aulia M. T.

2016-11-01

Biofilm is a way used by bacteria to survive from their environmental conditions by forming colony of bacteria. Specific characteristic in biofilm formation is the availability of matrix layer, known as extracellular polymer substance. Treatment using antibiotics may lead bacteria to be to resistant. Other treatments to reduce microbial, like biofilm, can be performed by using photodynamic therapy. Successful of this kind of therapy is induced by penetration of light and photosensitizer into target cells. The sonodynamic therapy offers greater penetrating capability into tissues. This research aimed to use sonodynamic therapy in reducing biofilm. Moreover, it compares also the killing efficacy of photodynamic therapy, sonodynamic therapy, and the combination of both therapeutic schemes (known as sono-photodynamic) to achieve higher microbial killing efficacy. Samples used are Staphylococcus aureus biofilm. Treatments were divided into 4 groups, i.e. group under ultrasound treatment with variation of 5 power levels, group of light treatment with exposure of 75s, group of combined ultrasound-light with variation of ultrasound power levels, and group of combined lightultrasound with variation of ultrasound power levels. Results obtained for each treatment, expressed in % efficacy of log CFU/mL, showed that the treatment of photo-sonodynamic provides greater killing efficacy in comparison to either sonodynamic and sono-photodynamic. The photo-sonodynamic shows also greater efficacy to photodynamic. So combination of light-ultrasound (photo-sonodynamic) can effectively kill microbial biofilm. The combined therapy will provide even better efficacy using exogenous photosensitizer.

Combination therapy of fenofibrate and ursodeoxycholic acid in patients with primary biliary cirrhosis who respond incompletely to UDCA monotherapy: a meta-analysis

PubMed Central

Zhang, Yan; Li, Sainan; He, Lei; Wang, Fan; Chen, Kan; Li, Jingjing; Liu, Tong; Zheng, Yuanyuan; Wang, Jianrong; Lu, Wenxia; Zhou, Yuqing; Yin, Qin; Xia, Yujing; Zhou, Yingqun; Lu, Jie; Guo, Chuanyong

2015-01-01

Background Although the effectiveness of treatment with ursodeoxycholic acid (UDCA) and fenofibrate for primary biliary cirrhosis (PBC) has been suggested by small trials, a systematic review to summarize the evidence has not yet been carried out. Methods A meta-analysis of all long-term randomized controlled trials comparing the combination of UDCA and fenofibrate with UDCA monotherapy was performed via electronic searches. Results Six trials, which included 84 patients, were assessed. Combination therapy with UDCA and fenofibrate was more effective than UDCA monotherapy in improving alkaline phosphatase (mean difference [MD]: −90.44 IU/L; 95% confidence interval [CI]: −119.95 to −60.92; P<0.00001), gamma-glutamyl transferase (MD: −61.58 IU/L; 95% CI: −122.80 to −0.35; P=0.05), immunoglobulin M (MD: −38.45 mg/dL; 95% CI: −64.38 to −12.51; P=0.004), and triglycerides (MD: −0.41 mg/dL; 95% CI: −0.82 to −0.01; P=0.05). However, their effects on pruritus (odds ratio [OR]: 0.39; 95% CI: 0.09–1.78; P=0.23), total bilirubin (MD: −0.05 mg/dL; 95% CI: −0.21 to 0.12; P=0.58), and alanine aminotransferase (MD: −3.31 IU/L; 95% CI: −14.60 to 7.97; P=0.56) did not differ significantly. This meta-analysis revealed no significant differences in the incidence of adverse events (OR: 0.21; 95% CI: 0.03–1.25; P=0.09) between patients treated with combination therapy and those treated with monotherapy. Conclusion In this meta-analysis, combination therapy with UDCA and fenofibrate was more effective in reducing alkaline phosphatase than UDCA monotherapy, but it did not improve clinical symptoms. There did not appear to be an increase in adverse events with combination therapy. PMID:26045661

Combined photoultrasonic treatment of infected wounds

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Menyaev, Yulian A.; Kalinin, Konstantin L.; Zmievskoy, Gregory N.; Velsher, Leonid Z.; Podkolzin, Alexander A.; Stakhanov, Mikhail L.; Gorchak, Yury Y.; Sarantsev, V. P.

2001-05-01

A new combined photoultrasonic (CPUS) technology for the treatment of infected wounds is suggested. The CPUS principal operation is based on the topical application of a photosensitizer followed by light irradiation in combination with low frequency ultrasonic (US) treatment of wounds. In CPUS, two methods - photodynamic (PDT) and ultrasonic therapies supplement each other beneficially and in conjunction provide a significant effect of deep suppurative inflammatory wounds treatment. The main advantages of the new technology are the combined application of an antibiotic solution and photodynamic therapy to destroy antibiotic- resistant microorganisms, an effective mixing of a photosensitizer in the wound, the US enhancement of photosensitizer impregnation into the membranes of bacteria, the US clearing of wound surface from necrotic products, an increased effective light dose exposure in the whole volume of the deep wound when the light does not penetrate totally inside the wound, an additional bactericidal effect under the US impact, and the combined effect of CPUS activation of the immune system.

Transcutaneous carbon dioxide enhances the antitumor effect of radiotherapy on oral squamous cell carcinoma.

PubMed

Iwata, Eiji; Hasegawa, Takumi; Ueha, Takeshi; Takeda, Daisuke; Saito, Izumi; Kawamoto, Teruya; Akisue, Toshihiro; Sakai, Yoshitada; Sasaki, Ryohei; Kuroda, Ryosuke; Komori, Takahide

2018-05-16

Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia. Considering the previous study, we hypothesized that transcutaneous CO2 may enhance the antitumor effect of RT on OSCC by improving intratumoral hypoxia, thereby overcoming radioresistance. In the present study, the combination of transcutaneous CO2 and RT significantly inhibited tumor growth compared with other treatments. This combination therapy also led to decreased expression of HIF-1α in parallel with increased expression of the cleaved forms of caspase-3-8-9 and PARP, which play essential roles in mitochondrial apoptosis. Additionally, the combination therapy increased the expression of ROS modulator 1 and subsequent mitochondrial ROS production, compared to RT alone. These results indicated that transcutaneous CO2 could potentially improve the antitumor effect of RT by decreasing the intratumoral hypoxia and increasing the mitochondrial apoptosis. Our findings indicated that CO2 therapy may be a novel adjuvant therapy in combination with RT for OSCC.

Multifunctional hollow gold nanoparticles designed for triple combination therapy and CT imaging.

PubMed

Park, Jaesook; Park, Jin; Ju, Eun Jin; Park, Seok Soon; Choi, Jinhyang; Lee, Jae Hee; Lee, Kyoung Jin; Shin, Seol Hwa; Ko, Eun Jung; Park, Intae; Kim, Chulhee; Hwang, Jung Jin; Lee, Jung Shin; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

2015-06-10

Hollow gold nanoparticles (HGNP) are a novel class of hybrid metal nanoparticles whose unique optical and morphological properties have spawned new applications including more effective cancer therapy. The shell thickness of HGNPs can tune the surface plasmon resonance to the near infrared light, resulting in photothermal ablation of tumors with optimal light penetration in tissue. The hollow cavity within a HGNP is able to accommodate a high payload of chemotherapeutic agents. They have also been used for enhancing radiosensitization in tumors during radiotherapy due to the high X-ray absorption capability of gold particles. However, no report has yet been published that utilize HGNPs for the triple combination therapy and CT imaging. In this study, we synthesized HGNPs which exhibit better response to radiation for therapy and imaging and demonstrated the effects of combined chemotherapy, thermal and radiotherapy. This combination strategy presented delayed tumor growth by 4.3-fold and reduced tumor's weight by 6.8-fold compared to control tumors. In addition, we demonstrated the feasibility of HGNP as a CT imaging agent. It is expected that translating these capabilities to human cancer patients could dramatically increase the antitumor effect and potentially overcome resistance to chemotherapeutic agents and radiation. Copyright © 2015 Elsevier B.V. All rights reserved.

Encopresis: A Structural/Strategic Approach to Family Therapy.

ERIC Educational Resources Information Center

McColgan, Edgar B.; And Others

1985-01-01

Reports treatment of a 9-year-old boy with primary encopresis combining structural and strategic approaches. Describes organizational features of the family, the contextual approach to therapy, individual and collective responses to therapy, and follow-up at 3 months and 1 1/2 years. Discusses effects of therapy on encopresis and on other…

Effects of mirror therapy combined with motor tasks on upper extremity function and activities daily living of stroke patients.

PubMed

Kim, Kyunghoon; Lee, Sukmin; Kim, Donghoon; Lee, Kyoungbo; Kim, Youlim

2016-01-01

[Purpose] The objective of this study was to investigate the effects of mirror therapy combined with exercise tasks on the function of the upper limbs and activities of daily living. [Subjects and Methods] Twenty-five stroke patients who were receiving physical therapy at K Hospital in Gyeonggi-do, South Korea, were classified into a mirror therapy group (n=12) and a conventional therapy group (n=13). The therapies were applied for 30 minutes per day, five times per week, for a total of four weeks. Upper limb function was measured with the Action Research Arm test, the Fugl-Meyer Assessment, and the Box and Block test, and activities of daily living were measured with the Functional Independence Measure. A paired test was performed to compare the intragroup differences between before training and after four weeks of therapy, and an independent t-test was performed to compare the differences between the two groups before and after four weeks of therapy. [Results] In the intragroup comparison, both groups showed significant differences between measurements taken before and after four weeks of therapy. In the intergroup comparison, the mirror therapy group showed significant improvements compared with the conventional therapy group, both in upper limb function and activities of daily living. [Conclusion] The findings of this study demonstrated that mirror therapy is more effective than conventional therapy for the training of stroke patients to improve their upper limb function and activities of daily living.

Recent advances in COPD disease management with fixed-dose long-acting combination therapies.

PubMed

Bateman, Eric D; Mahler, Donald A; Vogelmeier, Claus F; Wedzicha, Jadwiga A; Patalano, Francesco; Banerji, Donald

2014-06-01

Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β2-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD.

Combination therapy with ONO-KK1-300-01, a cathepsin K inhibitor, and parathyroid hormone results in additive beneficial effect on bone mineral density in ovariectomized rats.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Kawada, Naoki; Tanaka, Makoto; Imagawa, Akira; Ohmoto, Kazuyuki; Kawabata, Kazuhito

2016-01-01

This study examined the effects of a novel cathepsin K inhibitor, ONO-KK1-300-01 (KK1-300), used concurrently with parathyroid hormone (PTH) in ovariectomized (OVX) rats. KK1-300 (3 mg/kg, twice daily), alendronate (1 mg/kg, once daily) or vehicle were orally administered to OVX rats for 56 days, starting the day after ovariectomy, followed by combination treatment with or without PTH (3 μg/kg, subcutaneously three times a week) for another 28 days. OVX control animals exhibited a significant increase in both bone resorption (urinary deoxypyridinoline; DPD) and formation markers (serum osteocalcin) as well as microstructural changes associated with decreased bone mineral density (BMD). Combination treatment with KK1-300 and PTH significantly decreased urinary DPD and increased serum osteocalcin, indicating a sustained beneficial effect compared to the effect of each mono-therapy. On the other hand, combination therapy with alendronate and PTH weakened the PTH-induced increase in osteocalcin. In proximal tibia, combination treatment with KK1-300 and PTH increased BMD to a level significantly higher than that achieved following single treatment with KK1-300 or PTH alone. On the other hand, combination treatment with alendronate and PTH failed to produce any significant additive effect on BMD following single treatment with alendronate or PTH alone. Microstructural analysis revealed that the PTH-induced increase in bone formation (MS/BS and BFR/BS) was fully maintained following combination treatment with KK1-300 and PTH, but not following combination treatment with alendronate and PTH. These findings indicate that KK1-300, unlike alendronate, has an additive effect on the preventive action of PTH on bone loss in OVX rats.

Integrative Evaluation of Automated Massage Combined with Thermotherapy: Physical, Physiological, and Psychological Viewpoints.

PubMed

Kim, Do-Won; Lee, Dae Woon; Schreiber, Joergen; Im, Chang-Hwan; Kim, Hansung

2016-01-01

Various types of massages are reported to relieve stress, pain, and anxiety which are beneficial for rehabilitation; however, more comprehensive studies are needed to understand the mechanism of massage therapy. In this study, we investigated the effect of massage therapy, alone or in combination with infrared heating, on 3 different aspects: physical, physiological, and psychological. Twenty-eight healthy university students were subjected to 3 different treatment conditions on separate days, one condition per day: control, massage only, or massage with infrared heating. Physical (trunk extension [TE]; maximum power of erector spinae), physiological (heart-rate variability [HRV]; electroencephalogram [EEG]), and psychological (state-trait anxiety inventory [STAI]; visual analogue scale [VAS]) measurements were evaluated and recorded before and after each treatment condition. The results showed that massage therapy, especially when combined with infrared heating, significantly improved physical functioning, increased parasympathetic response, and decreased psychological stress and anxiety. In the current study, we observed that massage therapy contributes to various physical, physiological, and psychological changes, where the effect increases with thermotherapy.

Integrative Evaluation of Automated Massage Combined with Thermotherapy: Physical, Physiological, and Psychological Viewpoints

PubMed Central

Schreiber, Joergen

2016-01-01

Various types of massages are reported to relieve stress, pain, and anxiety which are beneficial for rehabilitation; however, more comprehensive studies are needed to understand the mechanism of massage therapy. In this study, we investigated the effect of massage therapy, alone or in combination with infrared heating, on 3 different aspects: physical, physiological, and psychological. Twenty-eight healthy university students were subjected to 3 different treatment conditions on separate days, one condition per day: control, massage only, or massage with infrared heating. Physical (trunk extension [TE]; maximum power of erector spinae), physiological (heart-rate variability [HRV]; electroencephalogram [EEG]), and psychological (state-trait anxiety inventory [STAI]; visual analogue scale [VAS]) measurements were evaluated and recorded before and after each treatment condition. The results showed that massage therapy, especially when combined with infrared heating, significantly improved physical functioning, increased parasympathetic response, and decreased psychological stress and anxiety. In the current study, we observed that massage therapy contributes to various physical, physiological, and psychological changes, where the effect increases with thermotherapy. PMID:28074179

Enhanced efficacy of combined temozolomide and bromodomain inhibitor therapy for gliomas using targeted nanoparticles.

PubMed

Lam, Fred C; Morton, Stephen W; Wyckoff, Jeffrey; Vu Han, Tu-Lan; Hwang, Mun Kyung; Maffa, Amanda; Balkanska-Sinclair, Elena; Yaffe, Michael B; Floyd, Scott R; Hammond, Paula T

2018-05-18

Effective treatment for glioblastoma (GBM) is limited by the presence of the blood-brain barrier (BBB) and rapid resistance to single agent therapies. To address these issues, we developed a transferrin-functionalized nanoparticle (Tf-NP) that can deliver dual combination therapies. Using intravital imaging, we show the ability of Tf-NPs to traverse intact BBB in mice as well as achieve direct tumor binding in two intracranial orthotopic models of GBM. Treatment of tumor-bearing mice with Tf-NPs loaded with temozolomide and the bromodomain inhibitor JQ1 leads to increased DNA damage and apoptosis that correlates with a 1.5- to 2-fold decrease in tumor burden and corresponding increase in survival compared to equivalent free-drug dosing. Immunocompetent mice treated with Tf-NP-loaded drugs also show protection from the effects of systemic drug toxicity, demonstrating the preclinical potential of this nanoscale platform to deliver novel combination therapies to gliomas and other central nervous system tumors.

Therapeutic synergism in the treatment of post-stroke arm paresis utilizing botulinum toxin, robotic therapy, and constraint-induced movement therapy.

PubMed

Takebayashi, Takashi; Amano, Satoru; Hanada, Keisuke; Umeji, Atsushi; Takahashi, Kayoko; Koyama, Tetsuo; Domen, Kazuhisa

2014-11-01

Botulinum toxin type A (BtxA) injection, constraint-induced movement therapy (CIMT), and robotic therapy (RT) each represent promising approaches to enhance arm motor recovery after stroke. To provide more effective treatment for a 50-year-old man with severe left spastic hemiparesis, we attempted to facilitate CIMT with adaptive approaches to extend the wrist and fingers using RT for 10 consecutive weeks after BtxA injection. This combined treatment resulted in substantial improvements in arm function and the amount of arm use in activities of daily living, and may be effective for stroke patients with severe arm paresis. However, we were unable to sufficiently prove the efficacy of combined treatment based only on a single case. To fully elucidate the efficacy of the combined approach for patients with severe hemiparesis after stroke, future studies of a larger number of patients are needed. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Effects of physiotherapy combined with sirolimus in a patient with vascular malformation: A case report.

PubMed

Akbayrak, Türkan; Orhan, Ceren; Baran, Emine; Kaya, Serap; Coskun, Gürsoy; Varan, Ali

2016-01-01

The aim of the present case report was to investigate the effects of a physiotherapy program combined with sirolimus in a child patient with upper extremity edema and joint limitation due to low-flow vascular malformation. This case report included an 11-year-old male patient (26 kg, 130 cm) diagnosed with congenital lymphovascular malformation on the left and right chest. The patient, who had edema on the upper left extremity and experienced joint limitations, was administered complete decongestive therapy (CDT) and manual therapy in combination with sirolimus. Physiotherapy included a total of 24 sessions, 3 sessions a week for 8 weeks. Following the physiotherapy, the patient was assigned to a home therapy program, and then the maintenance phase of the CDT was initiated. Evaluations were carried out at baseline, at the end of week 8, and after 12 months. Following the physiotherapy program combined with sirolimus, a decrease in extremity volume, an increase in joint movement range, and an improvement in disease-related complaints were observed. Physiotherapy methods combined with sirolimus may be an effective treatment method in patients with vascular malformations. However, further studies with larger sample size are warranted.

Dapagliflozin and saxagliptin tablets for adults with type 2 diabetes.

PubMed

Scheen, André J

2017-12-01

Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly). Expert commentary: Conclusions drawn from clinical trials investigating combination with the separate drugs are considered to apply to the fixed-dose combination (FDC) that demonstrates bioequivalence. Dual saxagliptin/dapagliflozin therapy is more potent than either monotherapy and can be used as an initial combination or a stepwise sequential approach. Dual therapy is generally well tolerated and may be used in special populations, with some limitations because of the presence of dapagliflozin. However, the latter may offer some advantages because of multiple effects attributed to SGLT2i. The best place of this dual combination for the management of T2D and the profile of patients who will make the most of this combined therapy remains to be defined.

Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti-inflammatory effects in mdx mice with Duchenne muscular dystrophy.

PubMed

Nio, Yasunori; Tanaka, Masayuki; Hirozane, Yoshihiko; Muraki, Yo; Okawara, Mitsugi; Hazama, Masatoshi; Matsuo, Takanori

2017-12-01

Duchenne muscular dystrophy (DMD) is the most common inherited muscular dystrophy. Patients experience DMD in their 20s from cardiac or respiratory failure related to progressive muscle wasting. Currently, the only treatments for the symptoms of DMD are available. Muscle fibrosis, a DMD feature, leads to reduced muscle function and muscle mass, and hampers pharmaceutical therapeutic efficacy. Although antifibrotic agents may be useful, none is currently approved. Phosphodiesterase 4 (PDE4) inhibitors have exhibited antifibrotic effects in human and animal models. In this study, we showed beneficial effects of the PDE4 inhibitor piclamilast in the DMD mdx mouse. Piclamilast reduced the mRNA level of profibrotic genes, including collagen 1A1, in the gastrocnemius and diaphragm, in the mdx mouse, and significantly reduced the Sirius red staining area. The PDE5 inhibitors sildenafil and tadalafil ameliorated functional muscle ischemia in boys with DMD, and sildenafil reversed cardiac dysfunction in the mdx mouse. Single-treatment piclamilast or sildenafil showed similar antifibrotic effects on the gastrocnemius; combination therapy showed a potent antifibrotic effect, and piclamilast and combination therapy increased peroxisome proliferator-activated receptor γ coactivator-1α mRNA in mouse gastrocnemius. In summary, we confirmed that piclamilast has significant antifibrotic effects in mdx mouse muscle and is a potential treatment for muscle fibrosis in DMD.-Nio, Y., Tanaka, M., Hirozane, Y., Muraki, Y., Okawara, M., Hazama, M., Matsuo, T. Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti-inflammatory effects in mdx mice with Duchenne muscular dystrophy. © FASEB.

Prevention of peripheral side-effects of transdermal hyoscine by adjunctive therapy with low dosage of pyridostigmine.

PubMed Central

Ziv, I; Versano, D; Ruach, M; Izraeli, S; Almog, S; Alhalel, A; Alkalay, M; Menahem, S; Tochner, Z

1992-01-01

1. The value of low dosage of pyridostigmine (30 mg three times daily) in preventing peripheral anti-muscarinic side effects of a transdermal controlled-release formulation of hyoscine, was tested in a double-blind placebo-controlled study, involving 47 healthy subjects. 2. Salivary excretion was repeatedly measured during 48 h of combined therapy of two transdermal hyoscine patches with pyridostigmine and 14 h after its cessation. Blood acetylcholinesterase activity was also measured, serving as an index of pyridostigmine bioavailability. 3. The adjunctive therapy with pyridostigmine was highly effective in preventing the substantial impairment in salivary flow caused by the transdermal formulation. An associated 23% inhibition of blood acetylcholinesterase activity was observed. 4. Small doses of pyridostigmine may therefore have a role in increasing the tolerability of transdermal hyoscine therapy. In some patients this drug combination might also allow some increment of the hyoscine dose. PMID:1524963

Effects of virtual reality training with modified constraint-induced movement therapy on upper extremity function in acute stage stroke: a preliminary study.

PubMed

Ji, Eun-Kyu; Lee, Sang-Heon

2016-11-01

[Purpose] The purpose of this study was to investigate the effects of virtual reality training combined with modified constraint-induced movement therapy on upper extremity motor function recovery in acute stage stroke patients. [Subjects and Methods] Four acute stage stroke patients participated in the study. A multiple baseline single subject experimental design was utilized. Modified constraint-induced movement therapy was used according to the EXplaining PLastICITy after stroke protocol during baseline sessions. Virtual reality training with modified constraint-induced movement therapy was applied during treatment sessions. The Manual Function Test and the Box and Block Test were used to measure upper extremity function before every session. [Results] The subjects' upper extremity function improved during the intervention period. [Conclusion] Virtual reality training combined with modified constraint-induced movement is effective for upper extremity function recovery in acute stroke patients.

Cell cycle-tailored targeting of metastatic melanoma: Challenges and opportunities.

PubMed

Haass, Nikolas K; Gabrielli, Brian

2017-07-01

The advent of targeted therapies of metastatic melanoma, such as MAPK pathway inhibitors and immune checkpoint antagonists, has turned dermato-oncology from the "bad guy" to the "poster child" in oncology. Current targeted therapies are effective, although here is a clear need to develop combination therapies to delay the onset of resistance. Many antimelanoma drugs impact on the cell cycle but are also dependent on certain cell cycle phases resulting in cell cycle phase-specific drug insensitivity. Here, we raise the question: Have combination trials been abandoned prematurely as ineffective possibly only because drug scheduling was not optimized? Firstly, if both drugs of a combination hit targets in the same melanoma cell, cell cycle-mediated drug insensitivity should be taken into account when planning combination therapies, timing of dosing schedules and choice of drug therapies in solid tumors. Secondly, if the combination is designed to target different tumor cell subpopulations of a heterogeneous tumor, one drug effective in a particular subpopulation should not negatively impact on the other drug targeting another subpopulation. In addition to the role of cell cycle stage and progression on standard chemotherapeutics and targeted drugs, we discuss the utilization of cell cycle checkpoint control defects to enhance chemotherapeutic responses or as targets themselves. We propose that cell cycle-tailored targeting of metastatic melanoma could further improve therapy outcomes and that our real-time cell cycle imaging 3D melanoma spheroid model could be utilized as a tool to measure and design drug scheduling approaches. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study.

PubMed

Haffmans, P M; Sival, R C; Lucius, S A; Cats, Q; van Gelder, L

2001-01-01

The purpose of this study was to evaluate the effects of bright light therapy combined with melatonin on motor restless behaviour in dementia. Double-blind, placebo-controlled, cross-over trial consisting of four periods. One week wash-out was followed by a 2-week period of light therapy in combination with placebo or melatonin. The second wash-out period of 1 week was followed by 2 weeks of treatment (cross-over). Twenty-four bed medium-stay psychogeriatric ward at a Dutch psychiatric teaching hospital. Ten patients, who met the criteria for dementia (DSM-IV) and motor restless behaviour (subscale 10 of the GIP), were included. Informed consent was obtained by proxy. All subjects were exposed during 2x5 consecutive days for 30 minutes to 10,000 lux bright light and randomly administered 2.5 mg melatonin or placebo at 22.00 h. Clinical Global Impression (CGI), Dutch version of the geriatric behavioural observation scale (GIP), Social Dysfunction and Aggression Scale (SDAS) were assessed after each wash-out and treatment period. Outcome criteria were CGI, assessing motor restless behaviour, the SDAS, measuring extrovert aggression and the GIP, assessing social, psychomotor and emotional behaviour. Six demented inpatients completed the trial. Positive effects were found for the treatment combined with placebo. Patients were less restless and more co-operative. The condition with melatonin showed no additional positive effects, additionally, patients became more aggressive and showed the same or more disturbed behaviour. Bright light therapy has a positive effect on motor restless behaviour. Light therapy in combination with melatonin has no positive effects. The results might be explained by a possible overshoot of chronobiological synchronisation or the timing of the melatonin intake. Copyright 2001 John Wiley & Sons, Ltd.

Efficacy and Safety of Combined vs. Single Renin–Angiotensin–Aldosterone System Blockade in Chronic Kidney Disease: A Meta-Analysis

PubMed Central

2013-01-01

BACKGROUND Although dual blockade of the renin–angiotensin–aldosterone system (RAAS) has gained popularity for the treatment of kidney disease, its benefits and potential risks have not been fully elucidated. We conducted a meta-analysis of all randomized controlled trials comparing the efficacy and safety of combined vs. single RAAS blockade therapy in chronic kidney disease (CKD). METHODS We performed a literature search using MEDLINE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, scientific abstracts from meetings, and bibliographies of retrieved articles. We used random-effects models to compute net changes and rate differences in variables. RESULTS Fifty-nine (25 crossover and 34 parallel-arm) randomized controlled trials (RCTs) comparing the efficacy and safety of combined vs. single RAAS blockade therapy in CKD were identified (4,975 patients). Combined RAAS blockade therapy was associated with a significant net decrease in glomerular filtration rate (GFR) (–1.8ml/min or ml/min/1.73 m2; P = 0.005), albuminuria (–90mg/g of creatinine; P = 0.001 or –32mg/day; P = 0.03), and proteinuria (–291mg/g; P = 0.003 or –363mg/day; P < 0.001). Combined RAAS blockade therapy was associated with a 9.4% higher rate of regression to normoalbuminuria and a 5% higher rate of achieving the blood pressure (BP) goal (as defined in individual trials). However, combined RAAS blockade therapy was associated with a significant net increase in serum potassium level, a 3.4% higher rate of hyperkalemia, and a 4.6% higher rate of hypotension. There was no effect on doubling of the serum creatinine level, hospitalization, or mortality. CONCLUSIONS Although combined RAAS blockade therapy in CKD is associated with a decrease in albuminuria and proteinuria, it is associated with a decrease in GFR and a higher incidence of hyperkalemia and hypotension relative to monotherapy. The potential long-term kidney benefits of combined RAAS blockade therapy require further study. PMID:23382494

[Magnetopuncture therapy in the combined corrective treatment of clinical manifestations of non-specific distress syndrome].

PubMed

El'chininov, N V

2009-01-01

The efficiency of a combined approach to the correction of clinical manifestations of non-specific distress syndrome was evaluated in patients with psychovegetative syndrome by comparing effects of phytoaeroionotherapy, graduated physical exercises, and soft tissue manual therapy in different combinations with simultaneous magnetopuncture therapy and without it. It was shown that above therapeutic modalities combined with magnetotherapy decreased the degree of asymmetry of both right and left heart meridians (by 60.5%) and interhemisphere asymmetry of blood flow in the system of internal carotid arteries (by 74.19%), reduced the tone of cerebral arterioles and veins (by 40.7% and 8.6% respectively), improved symptomes of depression and asthenia (by 23.2% and 63.9% respectively), increased mental performance quotient and activity indices (by 34.7% and 28.7% respectively). These changes were far less significant in the absence of by magnetopuncture therapy.

[Influence of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori eradication].

PubMed

Zhu, X Y; Du, J; Wu, J; Zhao, L W; Meng, X; Liu, G F

2017-08-08

Objective: To evaluate the efficacy and safety of Saccharomyces boulardii Sachets combined with bismuth quadruple therapy for initial Helicobacter pylori ( H . pylori ) eradication. Methods: From March 2014 to March 2015, 240 participants from the third hospital of Hebei medical university with H . pylori infection were recruited and randomized into three groups: Quadruple therapy group received bismuth potassium citrate 220 mg bid + Rabeprazole 10 mg bid + amoxicillin 1 000 mg bid+ furazolidone 100 mg bid for 10 days. Short-term group and long-term group received the same quadruple therapy for 10 days as above, as well as Saccharomyces boulardii Sachets 500 mg bid for 14 days and 28 days, respectively. H . pylori eradication was confirmed by (13)C/(14)C-UBT at least 4 weeks after completion of therapy. And side effects were investigated during the therapy. Results: The H . pylori eradication rates in quadruple therapy, short-term and long-term group were 80%, 87.5% and 87.5% by ITT analysis ( P =0.321) and 92.8%, 94.6% and 95.9% by PP analysis ( P =0.717), respectively. The overall side effect rate and occurrence of diarrhea and abdominal distension were significantly lower in short-term or long-term group as compared with quadruple therapy group( P =0.007, 0.003, 0.004), but there was no significant difference between the two probiotics groups. Conclusions: Both short and long-term Saccharomyces boulardii Sachets reduced the overall side effect rate and occurrence of diarrhea or abdominal distension when combined with bismuth quadruple therapy for initial H . pylori eradication and no difference was observed in efficacy or safety between the two groups.

Treatment of psoriasis and long-term maintenance using 308 nm excimer laser, clobetasol spray, and calcitriol ointment: a case series.

PubMed

Wong, Jillian W; Nguyen, Tien V; Bhutani, Tina; Koo, John Y M

2012-08-01

Psoriasis is a chronic inflammatory skin disease that is characterized by thickened red plaques covered with silvery scales. Excimer laser therapy is a cutting-edge advancement in UVB phototherapy. In contrast to traditional phototherapy, the 308 nm excimer laser only targets psoriasis plaques, while it spares uninvolved skin. It allows for treatment with a supra-erythmogenic dose of UVB irradiation. Targeted UVB therapy is a possible treatment especially for many who have failed topical treatments, systemic therapy, and traditional phototherapy. For safe and effective psoriasis treatment, a combination of therapies may be used, including a combination of laser treatment with topical medications. We present two cases demonstrating effective treatment with excimer laser in conjunction with clobetasol spray and calcitriol ointment for 12 weeks. Long-term near-clearance of psoriasis was sustained after 6 months and one-year follow up periods without further therapy.

The role of combination medical therapy in the treatment of acromegaly.

PubMed

Lim, Dawn Shao Ting; Fleseriu, Maria

2017-02-01

Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.

Antiinflammatory Effect of N-Acetylcysteine Combined with Exogenous Surfactant in Meconium-Induced Lung Injury.

PubMed

Mikolka, P; Kopincova, J; Mikusiakova, L Tomcikova; Kosutova, P; Calkovska, A; Mokra, D

2016-01-01

Neonatal meconium aspiration syndrome (MAS) can be treated by exogenous surfactant (S). However, aspirated meconium initiates local inflammation and oxidation which may inactivate surfactant and reduce its action. This experimental study estimated whether combined use of surfactant and the antioxidant N-acetylcysteine (NAC) can enhance effectiveness of therapy. Meconium-instilled rabbits were non-treated (M), treated with monotherapies (M + S, M + NAC), combined therapy (M + S + NAC), or received saline instead of meconium (controls, C). Surfactant therapy consisted of two lung lavages (BAL) with diluted Curosurf (5 mg phospholipids/ml, 10 ml/kg) followed by undiluted Curosurf (100 mg phospholipids/kg). N-acetylcysteine (Acc Injekt, 10 mg/kg) was given intravenously in M + S + NAC group 10 min after surfactant therapy. Animals were oxygen-ventilated for additional 5 h. Then, differential white cell count in the blood (WBC) was determined. Left lung was saline-lavaged and differential cell count in BAL was determined. In right lung tissue, wet/dry weight ratio, oxidation markers (TBARS, 3NT) and interleukines (IL-2, IL-6, IL-13, and TNFα) using ELISA and RT-PCR were estimated. Combined S + NAC therapy significantly decreased W/D ratio, TBARS, 3NT, and IL, whereas the effect of monotherapies (either S or NAC) was less obvious. In conclusion, addition of NAC to surfactant treatment may enhance the therapeutic outcome in MAS.

Chikungunya Virus: In Vitro Response to Combination Therapy With Ribavirin and Interferon Alfa 2a.

PubMed

Gallegos, Karen M; Drusano, George L; D Argenio, David Z; Brown, Ashley N

2016-10-15

We evaluated the antiviral activities of ribavirin (RBV) and interferon (IFN) alfa as monotherapy and combination therapy against chikungunya virus (CHIKV). Vero cells were infected with CHIKV in the presence of RBV and/or IFN alfa, and viral production was quantified by plaque assay. A mathematical model was fit to the data to identify drug interactions for effect. We ran simulations using the best-fit model parameters to predict the antiviral activity associated with clinically relevant regimens of RBV and IFN alfa as combination therapy. The model predictions were validated using the hollow fiber infection model (HFIM) system. RBV and IFN alfa were effective against CHIKV as monotherapy at supraphysiological concentrations. However, RBV and IFN alfa were highly synergistic for antiviral effect when administered as combination therapy. Simulations with our mathematical model predicted that a standard clinical regimen of RBV plus IFN alfa would inhibit CHIKV burden by 2.5 log10 following 24 hours of treatment. In the HFIM system, RBV plus IFN alfa at clinical exposures resulted in a 2.1-log10 decrease in the CHIKV burden following 24 hours of therapy. These findings validate the prediction made by the mathematical model. These studies illustrate the promise of RBV plus IFN alfa as a potential therapeutic strategy for the treatment of CHIKV infections. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Potent Antitumor Effects of Combination Therapy With IFNs and Monocytes in Mouse Models of Established Human Ovarian and Melanoma Tumors

PubMed Central

Nakashima, Hideyuki; Miyake, Kotaro; Clark, Christopher R; Bekisz, Joseph; Finbloom, Joel; Husain, Syed R.; Baron, Samuel; Puri, Raj K.; Zoon, Kathryn C.

2012-01-01

Interferon-activated monocytes are known to exert cytocidal activity against tumor cells in vitro. Here, we have examined whether a combination of IFN-α2a and IFN-γ and human monocytes mediate significant antitumor effects against human ovarian and melanoma tumor xenografts in mouse models. OVCAR-3 tumors were treated i.t. with monocytes alone, IFN-α2a and IFN-γ alone or combination of all three on day 0, 15 or 30 post-tumor implantation. Mice receiving combination therapy beginning day 15 showed significantly reduced tumor growth and prolonged survival including complete regression in 40% mice., Tumor volumes measured on day 80 in mice receiving combination therapy (206 mm3) were significantly smaller than those of mice receiving the IFNs alone (1041 mm3), monocytes alone (1111 mm3) or untreated controls (1728 mm3). Similarly, combination therapy with monocytes and IFNs of much larger tumor also inhibited OVCAR-3 tumor growth. Immunohistochemistry studies showed a large number of activated macrophages (CD31+/CD68+) infiltrating into OVCAR-3 tumors and higher densities of IL-12, IP10 and NOS2, markers of M1 (classical) macrophages in tumors treated with combination therapy compared to the controls. Interestingly, IFNs activated macrophages induced apoptosis of OVCAR-3 tumor cells as monocytes alone or IFNs alone did not mediate significant apoptosis. Similar antitumor activity was observed in the LOX melanoma mouse model, but not as profound as seen with the OVCAR-3 tumors. Administration of either mixture of monocytes and IFN-α2a or monocytes and IFN-γ did not inhibit Lox melanoma growth; however a significant inhibition was observed when tumors were treated with a mixture of monocytes, IFN-α2a and IFN-γ. These results indicate that monocytes and both IFN-α2a and IFN-γ may be required to mediate profound antitumor effect against human ovarian and melanoma tumors in mouse models. PMID:22159517

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

PubMed Central

Olesovsky, Chris; Kapoor, Anil

2016-01-01

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

Combination therapy with telmisartan and parecoxib induces regression of endometriotic lesions.

PubMed

Nenicu, Anca; Gu, Yuan; Körbel, Christina; Menger, Michael D; Laschke, Matthias W

2017-08-01

Telmisartan suppresses the development of endometriotic lesions. However, the drug also up-regulates the expression of COX-2, which has been suggested to promote the progression of endometriosis. Accordingly, in the present study we analysed whether a combination therapy with telmisartan and a COX-2 inhibitor may be more effective in the treatment of endometriotic lesions than the application of telmisartan alone. Endometriotic lesions were induced in the peritoneal cavity of C57BL/6 mice, which were treated daily with an i.p. injection of telmisartan (10 mg·kg -1 ), parecoxib (5 mg·kg -1 ), a combination of telmisartan and parecoxib or vehicle. Therapeutic effects on lesion survival, growth, vascularization, innervation and protein expression were studied over 4 weeks by high-resolution ultrasound imaging as well as immunohistochemical and Western blot analyses. Telmisartan-treated lesions exhibited a significantly reduced lesion volume when compared with vehicle-treated controls and parecoxib-treated lesions. This inhibitory effect of telmisartan was even more pronounced when it was used in combination with parecoxib. The combination therapy resulted in a reduced microvessel density as well as lower numbers of proliferating Ki67-positive cells and higher numbers of apoptotic cleaved caspase-3-positive stromal cells within the lesions. This was associated with a lower expression of COX-2, MMP-9 and p-Akt/Akt when compared with controls. The application of the two drugs further inhibited the ingrowth of nerve fibres into the lesions. Combination therapy with telmisartan and a COX-2 inhibitor represents a novel, effective pharmacological strategy for the treatment of endometriosis. © 2017 The British Pharmacological Society.

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

PubMed

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

Radiation therapy in the management of patients with mesothelioma

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

Gordon, W. Jr.; Antman, K.H.; Greenberger, J.S.

The results of radiation therapy in the management of 27 patients with malignant mesothelioma were reviewed. Eight patients were treated with a curative intent combining attempted surgical excision of tumor (thoracic in 6 and peritoneal in 2), aggressive radiation therapy, and combination chemotherapy using an adriamycin-containing regimen. One patient achieved a 2-year disease-free inteval followed by recurrence of tumor above the thoracic irradiation field. This patient was retreated with localized irradiation and is disease-free after 5 years of initial diagnosis. One patient has persistent abdominal disease at 18 months; the other 6 patients suffered local recurrence within 8-13 months ofmore » initiation of treatment. Radiation therapy was used in 19 other patients who received 29 courses for palliation of dyspnea, superior vena cava syndrome, dysphagia, or neurological symptoms of brain metastasis. A palliation index was used to determine the effectiveness of irradiation and revealed that relief of symptoms was complete or substantial in 5 treatment courses, moderately effective in 6 courses and inadequate in 18 treatment courses. Adequate palliation strongly correlated with a dose at or above 4,000 rad in 4 weeks. The management of patients with mesothelioma requires new and innovative approaches to increase the effectiveness of radiation therapy and minimize the significant potential combined toxicity of pulmonary irradiation and adriamycin.« less

Application and possible mechanisms of combining LLLT (low level laser therapy), infrared hyperthermia and ionizing radiation in the treatment of cancer

NASA Astrophysics Data System (ADS)

Abraham, Edward H.; Woo, Van H.; Harlin-Jones, Cheryl; Heselich, Anja; Frohns, Florian

2014-02-01

Benefit of concomitant infrared hyperthermia and low level laser therapy and ionizing radiation is evaluated in this study. The purpose/objectives: presentation with locally advanced bulky superficial tumors is clinically challenging. To enhance the efficacy of chemotherapy and IMRT (intensity-modulated radiation therapy) and/or electron beam therapy we have developed an inexpensive and clinically effective infrared hyperthermia approach that combines black-body infrared radiation with halogen spectrum radiation and discrete wave length infrared clinical lasers LLLT. The goal is to produce a composite spectrum extending from the far infrared to near infrared and portions of the visible spectrum with discrete penetrating wavelengths generated by the clinical infrared lasers with frequencies of 810 nm and/or 830 nm. The composite spectrum from these sources is applied before and after radiation therapy. We monitor the surface and in some cases deeper temperatures with thermal probes, but use an array of surface probes as the limiting safe thermal constraint in patient treatment while at the same time maximizing infrared entry to deeper tissue layers. Fever-grade infrared hyperthermia is produced in the first centimeters while non-thermal infrared effects act at deeper tissue layers. The combination of these effects with ionizing radiation leads to improved tumor control in many cancers.

E phage gene transfection associated to chemotherapeutic agents increases apoptosis in lung and colon cancer cells.

PubMed

Rama, Ana R; Prados, Jose; Melguizo, Consolacion; Alvarez, Pablo J; Ortiz, Raúl; Madeddu, Roberto; Aranega, Antonia

2011-01-01

The limited ability of conventional therapies to achieve the long-term survival of metastatic lung and colon cancer patients suggests the need for new treatment options. In this respect, genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the activity of drugs, and combined therapies involving such genes and classical antitumoral drugs have been studied intensively. The E gene from phiX174 encodes a membrane protein with a toxic domain that leads to a decrease in tumour cell growth rates. Therefore, in order to improve the anti-tumour effects of currently used chemotherapeutic drugs on cancer cells, we investigated the association of the E suicide gene with these antineoplastic drugs. The E gene has antitumoral effects in both lung and colon cancer cells. In addition, expression of this gene induces ultrastructural changes in lung cancer transfected cells (A-549), although the significance of these changes remains unknown. The effect of combined therapy (gene and cytotoxic therapy) enhances the inhibition of tumour cell proliferation in comparison to single treatments. Indeed, our in vitro results indicate that an experimental therapeutic strategy based on this combination of E gene therapy and cytotoxic drugs may result in a new treatment strategy for patients with advanced lung and colon cancer.

Intense pulsed light, near infrared pulsed light, and fractional laser combination therapy for skin rejuvenation in Asian subjects: a prospective multi-center study in China.

PubMed

Tao, Li; Wu, Jiaqiang; Qian, Hui; Lu, Zhong; Li, Yuanhong; Wang, Weizhen; Zhao, Xiaozhong; Tu, Ping; Yin, Rui; Xiang, Leihong

2015-09-01

Ablative skin rejuvenation therapies have limitations for Asian people, including post-inflammatory hyperpigmentation and long down time. Non-ablative lasers are safer but have limited efficacy. This study is to investigate the safety and efficacy of a combination therapy consisting of intense pulsed light (IPL), near infrared (NIR) light, and fractional erbium YAG (Er:YAG) laser for skin rejuvenation in Asian people. This study recruited 113 subjects from six sites in China. Subjects were randomly assigned to a full-face group, who received combination therapy, and split-face groups, in which one half of the face received combination therapy and the other half received IPL monotherapy. Each subject received five treatment sessions during a period of 90 days. Subjects were followed up at 1 and 3 months post last treatment. Three months after last treatment, the full-face group (n = 57) had a global improvement rate of 29 % and 29 % for wrinkles, 32 % for skin texture, 33 % for pigment spots, 28 % for pore size, respectively. For patients in the split-face groups (n = 54), monotherapy side had a global improvement rate of 23 % and 20 % for wrinkles, 27 % for skin texture, 25 % for pigment spots, 25 % for pore size, respectively. Both combination therapy and monotherapy resulted in significant improvements at the follow-up visits compared to baseline (P < 0.001). Combination therapy showed significantly greater improvements compared to monotherapy at two follow-up visits (P < 0.05). Combination therapy is a safe and more effective strategy than IPL monotherapy for skin rejuvenation in Asian people.

Silver-loaded nanotubular structures enhanced bactericidal efficiency of antibiotics with synergistic effect in vitro and in vivo.

PubMed

Xu, Na; Cheng, Hao; Xu, Jiangwen; Li, Feng; Gao, Biao; Li, Zi; Gao, Chenghao; Huo, Kaifu; Fu, Jijiang; Xiong, Wei

2017-01-01

Antibiotic-resistant bacteria have become a major issue due to the long-term use and abuse of antibiotics in treatments in clinics. The combination therapy of antibiotics and silver (Ag) nanoparticles is an effective way of both enhancing the antibacterial effect and decreasing the usage of antibiotics. Although the method has been proved to be effective in vitro, no in vivo tests have been carried out at present. Herein, we described a combination therapy of local delivery of Ag and systemic antibiotics treatment in vitro in an infection model of rat. Ag nanoparticle-loaded TiO 2 nanotube (NT) arrays (Ag-NTs) were fabricated on titanium implants for a customized release of Ag ion. The antibacterial properties of silver combined with antibiotics vancomycin, rifampin, gentamicin, and levofloxacin, respectively, were tested in vitro by minimum inhibitory concentration (MIC) assay, disk diffusion assay, and antibiofilm formation test. Enhanced antibacterial activity of combination therapy was observed for all the chosen bacterial strains, including gram-negative Escherichia coli (ATCC 25922), gram-positive Staphylococcus aureus (ATCC 25923), and methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591 and ATCC 43300). Moreover, after a relative short (3 weeks) combinational treatment, animal experiments in vivo further proved the synergistic antibacterial effect by X-ray and histological and immunohistochemical analyses. These results demonstrated that the combination of Ag nanoparticles and antibiotics significantly enhanced the antibacterial effect both in vitro and in vivo through the synergistic effect. The strategy is promising for clinical application to reduce the usage of antibiotics and shorten the administration time of implant-associated infection.

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

PubMed Central

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

PubMed Central

Glasgow, Micah D. K.; Chougule, Mahavir B.

2016-01-01

Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

An updated review of the efficacy of cupping therapy.

PubMed

Cao, Huijuan; Li, Xun; Liu, Jianping

2012-01-01

Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted.

Antitumor activity of ZD6126, a novel vascular-targeting agent, is enhanced when combined with ZD1839, an epidermal growth factor receptor tyrosine kinase inhibitor, and potentiates the effects of radiation in a human non-small cell lung cancer xenograft model.

PubMed

Raben, David; Bianco, Cataldo; Damiano, Vincenzo; Bianco, Roberto; Melisi, Davide; Mignogna, Chiara; D'Armiento, Francesco Paolo; Cionini, Luca; Bianco, A Raffaele; Tortora, Giampaolo; Ciardiello, Fortunato; Bunn, Paul

2004-08-01

Targeting the tumor vasculature may offer an alternative or complementary therapeutic approach to targeting growth factor signaling in lung cancer. The aim of these studies was to evaluate the antitumor effects in vivo of the combination of ZD6126, a tumor-selective vascular-targeting agent; ZD1839 (gefitinib, Iressa), an epidermal growth factor receptor tyrosine kinase inhibitor; and ionizing radiation in the treatment of non-small cell lung cancer xenograft model. Athymic nude mice with established flank A549 human non-small cell lung cancer xenograft model xenografts were treated with fractionated radiation therapy, ZD6126, ZD1839, or combinations of each treatment. ZD6126 (150 mg/kg) was given i.p. the day after each course of radiation. Animals treated with ZD1839 received 100 mg/kg per dose per animal, 5 or 7 days/wk for 2 weeks. Immunohistochemistry was done to evaluate the effects on tumor growth using an anti-Ki67 monoclonal antibody. Effects on tumor-induced vascularization were quantified using an anti-factor VIII-related antigen monoclonal antibody. ZD6126 attenuated the growth of human A549 flank xenografts compared with untreated animals. Marked antitumor effects were observed when animals were treated with a combination of ZD6126 and fractionated radiation therapy with protracted tumor regression. ZD6126 + ZD1839 resulted in a greater tumor growth delay than either agent alone. Similar additive effects were seen with ZD1839 + fractionated radiation. Finally, the addition of ZD6126 to ZD1839 and radiation therapy seemed to further improve tumor growth control, with a significant tumor growth delay compared with animals treated with single agent or with double combinations. Immunohistochemistry showed that ZD1839 induced a marked reduction in A549 tumor cell proliferation. Both ZD1839 and ZD6126 treatment substantially reduced tumor-induced angiogenesis. ZD6126 caused marked vessel destruction through loss of endothelial cells and thrombosis, substantially increasing the level of necrosis seen when combined with radiation therapy. The combination of radiation therapy, ZD6126, and ZD1839 induced the greatest effects on tumor growth and angiogenesis. This first report shows that a selective vascular-targeting agent (ZD6126) + an anti-epidermal growth factor receptor agent (ZD1839) and radiation have additive in vivo effects in a human cancer model. Targeting the tumor vasculature offers an excellent strategy to enhance radiation cytotoxicity. Polytargeted therapy with agents that interfere with both growth factor and angiogenic signaling warrants further investigation.

Effect of manual therapy techniques on headache disability in patients with tension-type headache. Randomized controlled trial.

PubMed

Espí-López, G V; Rodríguez-Blanco, C; Oliva-Pascual-Vaca, A; Benítez-Martínez, J C; Lluch, E; Falla, D

2014-12-01

Tension-type headache (TTH) is the most common type of primary headache however there is no clear evidence as to which specific treatment is most effective or whether combined treatment is more effective than individual treatments. To assess the effectiveness of manual therapy techniques, applied to the suboccipital region, on aspects of disability in a sample of patients with tension-type headache. Randomized Controlled Trial. Specialized centre for headache treatment. Seventy-six (62 women) patients (age: 39.9 ± 10.9 years) with episodic chronic TTH. Patients were randomly divided into four treatment groups: 1) suboccipital soft tissue inhibition; 2) occiput-atlas-axis manipulation; 3) combined treatment of both techniques; 4) control. Four sessions were applied over 4 weeks and disability was assessed before and after treatment using the Headache Disability Inventory (HDI). Headache frequency, severity and the functional and emotional subscales of the questionnaire were assessed. Photophobia, phonophobia and pericranial tenderness were also monitored. Headache frequency was significantly reduced with the manipulative and combined treatment (P<0.05), and the severity and functional subscale of the HDI changed in all three treatment groups (P<0.05). Manipulation treatment also reduced the score on the emotional subscale of the HDI (P<0.05). The combined intervention showed a greater effect at reducing the overall HDI score compared to the group that received suboccipital soft tissue inhibition and to the control group (both P<0.05). In addition, photophobia, phonophobia and pericranial tenderness only improved in the group receiving combined therapy (P<0.05). When given individually, suboccipital soft tissue inhibition and occiput-atlas-axis manipulation resulted in changes in different parameters related to the disability caused by TTH. However, when the two treatments were combined, effectiveness was noted for all aspects of disability and other symptoms including photophobia, phonophobia and pericranial tenderness. Although individual manual therapy treatments showed a positive change in headache features, measures of photophobia, photophobia and pericranial tenderness only improved in the group that received the combined treatment suggesting that combined treatment is the most appropriate for symptomatic relief of TTH.

Additive effect by combination of Akt inhibitor, MK-2206, and PDGFR inhibitor, tyrphostin AG 1296, in suppressing anaplastic thyroid carcinoma cell viability and motility.

PubMed

Che, Huan-Yong; Guo, Hang-Yuan; Si, Xu-Wei; You, Qiao-Ying; Lou, Wei-Ying

2014-01-01

The phosphatidylinositol-3-kinase/Akt pathway and receptor tyrosine kinases regulate many tumorigenesis related cellular processes including cell metabolism, cell survival, cell motility, and angiogenesis. Anaplastic thyroid carcinoma (ATC) is a rare type of thyroid cancer with no effective systemic therapy. It has been shown that Akt activation is associated with tumor progression in ATC. Here we observed the additive effect between an Akt inhibitor (MK-2206) and a novel platelet-derived growth factor receptor inhibitor (tyrphostin AG 1296) in ATC therapy. We found an additive effect between MK-2206 and tyrphostin AG 1296 in suppressing ATC cell viability. The combination of MK-2206 and tyrphostin AG 1296 induces additive apoptosis, additive suppression of the Akt signaling pathway, as well as additive inhibition of cell migration and invasion of ATC cells. Furthermore, the combination of MK-2206 and tyrphostin AG 1296 induced additive suppression of ATC tumor growth in vivo. In summary, our studies suggest that the combination of Akt and receptor tyrosine kinase inhibitors may be an efficient therapeutic strategy for ATC treatment, which might shed new light on ATC therapy.

M1-like macrophages change tumor blood vessels and microenvironment in murine melanoma

PubMed Central

Kamińska, Natalia; Matuszczak, Sybilla; Cichoń, Tomasz; Pamuła-Piłat, Jolanta; Czapla, Justyna; Smolarczyk, Ryszard; Skwarzyńska, Daria; Kulik, Klaudia; Szala, Stanisław

2018-01-01

Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression. Here, we demonstrated that combination of endoglin-based DNA vaccine with interleukin 12 repolarizes TAMs from tumor growth-promoting M2-like phenotype to tumor growth-inhibiting M1-like phenotype. Combined therapy enhances tumor infiltration by CD4+, CD8+ lymphocytes and NK cells. Depletion of TAMs as well as CD8+ lymphocytes and NK cells, but not CD4+ lymphocytes, reduces the effect of combined therapy. Furthermore, combined therapy improves tumor vessel maturation, perfusion and reduces hypoxia. It caused that suboptimal doses of doxorubicin reduced the growth of tumors in mice treated with combined therapy. To summarize, combination of antiangiogenic drug and immunostimulatory agent repolarizes TAMs phenotype from M2-like (pro-tumor) into M1-like (anti-tumor) which affects the structure of tumor blood vessels, improves the effect of chemotherapy and leads to tumor growth regression. PMID:29320562

Clinical efficacy of flumetasone/salicylic acid ointment combined with 308-nm excimer laser for treatment of psoriasis vulgaris.

PubMed

Dong, Jie; He, Yanling; Zhang, Xiuying; Wang, Yixuan; Tian, Yongjing; Wang, Jie

2012-06-01

To compare the clinical efficacy and safety of combining flumetasone ointment with 308-nm excimer laser therapy vs. 308-nm excimer laser monotherapy for the treatment of psoriasis vulgaris. Forty patients with psoriasis vulgaris were recruited; 20 were treated with flumetasone ointment plus 308-nm excimer laser therapy, and the other 20 received only excimer laser monotherapy. The flumetasone ointment was applied topically twice a day, and laser treatments were scheduled twice weekly for a total of 10 treatments. Clinical efficacy was evaluated in a blinded manner by two independent physicians using photographs taken before and after treatment. Of the 40 patients who received and completed the entire course of therapy, the psoriasis area and severity index score was improved by 82.51 ± 11.24% and 72.01 ± 20.94% in the combination group and laser group, respectively (P > 0.05), and the average cumulative dose was 5.06 ± 2.20 j/cm(2) in the combination group and 7.75 ± 2.25 j/cm(2) in the laser-only group, respectively (P < 0.05). The clinical data suggest that combination treatment using flumetasone ointment and a 308-nm excimer laser is superior to laser monotherapy for treatment of psoriasis vulgaris. The combination therapy can increase effectiveness and decrease the total laser dose, thus potentially reducing side effects. © 2012 John Wiley & Sons A/S.

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

PubMed

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

2014-04-01

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

Graphitic carbon nitride nanosheet@metal-organic framework core-shell nanoparticles for photo-chemo combination therapy

NASA Astrophysics Data System (ADS)

Chen, Rui; Zhang, Jinfeng; Wang, Yu; Chen, Xianfeng; Zapien, J. Antonio; Lee, Chun-Sing

2015-10-01

Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed as a promising platform for bioimaging and drug delivery. On the other hand, combination therapies using multiple approaches are demonstrated to achieve much enhanced efficacy. Herein, we report, for the first time, core-shell nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF shell while simultaneously carrying a chemotherapeutic drug for effective combination therapy. In this work, core-shell nanoparticles of zeolitic-imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g-C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8 shell of the core-shell nanoparticles. The combination of the chemotherapeutic effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue fluorescence of g-C3N4 nanosheets provide the additional function of dual-color imaging for monitoring the drug release process.Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed as a promising platform for bioimaging and drug delivery. On the other hand, combination therapies using multiple approaches are demonstrated to achieve much enhanced efficacy. Herein, we report, for the first time, core-shell nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF shell while simultaneously carrying a chemotherapeutic drug for effective combination therapy. In this work, core-shell nanoparticles of zeolitic-imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g-C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8 shell of the core-shell nanoparticles. The combination of the chemotherapeutic effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue fluorescence of g-C3N4 nanosheets provide the additional function of dual-color imaging for monitoring the drug release process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04436g

[Evaluate the efficacy of combination therapy of ultrasound and currents of TENS professionally active in patients with pain of the lumbar spine].

PubMed

Krukowska, Jolanta; Dudkiewicz, Iwona; Balcerzak, Ewa; Linek, Przemysław; Kulma, Dariusz; Miller, Elibieta

2014-01-01

Back pain most often affects people whose work is related to the load while performing activities related to lifting and in addition to the method and type of work performed, as well as office workers. The aim of the study is to evaluate the efficacy of combination therapy of ultrasound and TENS in the analgesic effect in patients with disorders of the lumbar spine. The study group consisted of 115 patients aged from 24 to 65 years (mean 45.22 +/- 10.38 years) with pain complaints in the lumbar degenerative against overload and, as a result of long-term work involved in taking a forced static position or sitting. Twice (before and after treatment) pain intensity was assessed using of the modified questionnaire of indicators according to Laitinen and scale VAS and physical fitness bythe Oswestry questionnaire (ODI--Oswestry Disability Index). It has been demonstrated greater analgesic efficacy of combination therapy than the monotherapy, which had a characterizing effect on the improvement of mobility of patients according to the Oswestry questionnaire. Afterthe completion of the combination therapy was observed the highly statistical higher than in the monotherapy groups, reducing the intensity and frequency of pain, increase physical activity and reduce quantities medications you are taking. Combination antiretroviral the action of ultrasound and currentsTENS has a more effective analgesic effect and improve the efficiency of patients with pain in the lumbar spine than monotherapy with ultrasound or TENS currents. Enables faster recovery professional and social activity and a reduction in sickness absence at work.

[The fundamental characteristics and application of psychological intervention on acupuncture therapy].

PubMed

Gu, Zhong-yue

2009-06-01

The process of acupuncture therapy is a complete combination of linguistic suggestion, cognitive behavioral therapy and body treatment systems. Differentiation of syndrome and diagnosis play the role of linguistic suggestion, while the magnified phenomenon of bio-information and possible manipulation on the arrival of qi play the role of cognitive behavioral therapy. The objective effectiveness of acupuncture not only includes clinical treatment, but also contains reducing or preventing foreign malignant psychological stimulation, regulating the concentration of 5-hydroxytryptamine and dopamine, and keeping the inter environment stable etc. According to the process of treating patient as followed with "telling his sickness, establishing his confidence, inducing his feeling and relieving his suffering", treatment is carried out with taking the arrival of qi as the key point, combining the steps of characteristics of psychological treatment effectively, and cooperating with psychological and body treatments to obtain effectiveness. It accords with Chinese medical theories of simultaneous treatment of the branch and root as well as effectiveness following arrival of qi.

Initial results utilizing combination therapy for patients with a suboptimal response to either alprostadil or sildenafil monotherapy.

PubMed

Mydlo, J H; Volpe, M A; Macchia, R J

2000-07-01

Intraurethral alprostadil and oral sildenafil are useful in selected patients. However, there continues to be a significant treatment failure rate. Since their mechanisms of action are different, we wanted to evaluate the effectiveness of combination therapy. Of 214 patients treated for erectile dysfunction (ED), 65 were not fully satisfied with the firmness of their erections via monotherapy. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Group I consisted of 33 patients who tried maximal dose intraurethral alprostadil monotherapy initially, followed by the maximal dose of sildenafil monotherapy, and were still unsatisfied. Group II consisted of 32 patients who tried the maximal dose sildenafil monotherapy initially, followed by the maximal dose of alprostadil monotherapy, and were also unsatisfied. There 65 patients then underwent combination therapy. 60 out of the 65 patients stated they were satisfied with combination therapy. Questionnaire scores for erectile function were 23.1+/-2.0 (114%) for combination therapy vs. 19.2+/-1.8 (77%) and 15.2+/-1.6 (41%) for sildenafil and alprostadil monotherapies (p<0.05). There were no significant differences in responses between the two groups. The men also reported improvement in intercourse and overall satisfaction. Combination therapy may be an option for motivated patients who have a suboptimal response from monotherapy.

Effects of Aquatic Therapy and Land-Based Therapy versus Land-Based Therapy Alone on Range of Motion, Edema, and Function after Hip or Knee Replacement: A Systematic Review and Meta-analysis

PubMed Central

Shields, Nora

2015-01-01

ABSTRACT Purpose: To determine whether aquatic therapy in combination with land-based therapy improves patient outcomes after hip or knee arthroplasty compared with land-based therapy alone. Methods: For this systematic review, six online databases (MEDLINE, CINAHL, AMED, EMBASE, Cochrane, and PEDro) were searched from the earliest date available until September 2013. Controlled trials published in English in a peer-reviewed journal that compared aquatic therapy in combination with land-based therapy with land-based therapy alone were included; trial quality was assessed using the PEDro scale. Data were presented as standardized mean differences (SMDs), their associated 95% CIs, and meta-analyses. Results: Three small trials of moderate quality were included in the qualitative analysis. Meta-analysis of two of these studies found moderate-quality evidence that aquatic therapy in combination with land-based therapy improves functional outcomes (SMD=0.53; 95% CI, 0.03–1.03), knee range of motion (measured in knee or hip arthroplasty; SMD=0.78; 95% CI, 0.27–1.29), and edema (SMD=−0.66; 95% CI, −1.16 to −0.15) compared with land-based therapy alone. The results for improved functional outcomes were not considered clinically significant. Conclusions: It is not possible to draw confident conclusions from this review because of the small number of studies of limited quality and the modest differences found. Further studies of sound methodological quality are required to confirm the results. Economic analysis alongside randomized controlled trials is needed to examine the cost-effectiveness of these clinical outcomes. PMID:25931664

Pain therapy with oxycodone/naloxone prolonged-release combination: case report.

PubMed

Błaszczyk, Feliks; Droń, Aleksandra

2013-01-01

Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent - morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin(®) (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control.

Itchy, Scaly Skin? Living with Psoriasis

MedlinePlus

... treatment—medicines taken by pill or injection. Combination Therapy. Combining different treatments can prove more effective. Psychological Support. People with moderate to severe psoriasis may ...

A meta-analysis of cytokine-induced killer cells therapy in combination with minimally invasive treatment for hepatocellular carcinoma.

PubMed

Li, Xiaofeng; Dai, Dong; Song, Xiuyu; Liu, Jianjing; Zhu, Lei; Xu, Wengui

2014-10-01

There was a continuing controversy on whether the adoptive transfusion of cytokine-induced killer cells (CIK) therapy should have been recommended to reduce the recurrence and metastasis of hepatocellular carcinoma (HCC) after minimally invasive therapy such as TACE (transarterial chemoembolization) or TACE plus RFA (radiofrequency ablation) treatment. The meta-analysis was conducted to compare the effectiveness of CIK cells transfusion therapy combined with TACE or TACE plus RFA treatment with that of minimally invasive therapy alone. Relevant studies were identified by electronic search using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Overall survival (OS) rates and recurrence-free survival (RFS) rates were compared as the major outcome measures. The meta-analysis was divided into two sub-studies (sub-study 1: CIK+TACE+RFA versus TACE+RFA; sub-study 2: CIK+TACE versus TACE) to avoid the risk of bias as we could. Meta-analysis data suggested that CIK cells transfusion therapy combined with TACE plus RFA treatment was associated with higher 1-year RFS rate (odds ratio [OR]=2.46) and 1-year, 2-year OS rates (OR: 1-year=2.09; 3-year=2.16) than TACE plus RFA treatment alone in sub-study 1. For sub-study 2, there were significant differences between CIK+TACE group and TACE group for OS rates (OR: half-year=3.29; 1-year=3.71; 2-year=7.37). CIK cells transfusion therapy truly showed a synergistic effect for HCC patients after minimally invasive treatment especially for a long-term survival. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project.

PubMed

Franchi, F; Lazzeri, C; Foschi, M; Tosti-Guerra, C; Barletta, G

2002-08-01

Pharmacological and clinical studies on the effects of angiotensin-converting enzyme (ACE) inhibitors support the idea of a central role played Angiotensin II which is able to cause cardiovascular and renal diseases also independently of its blood pressure elevating effects. The present investigation was aimed at evaluating the effect(s) of three different pharmacological regimens on both blood pressure and sympathetic drive in uncomplicated essential hypertension, by means of blood pressure laboratory measurements and ambulatory monitoring, 24-h heart rate variability and plasma noradrenaline levels. Thus, an ACE-inhibitor monotherapy (trandolapril, 2 mg/day), an AT(1)-receptor antagonist monotherapy (irbesartan, 300 mg/day), their low-dose combination (0.5 mg/day plus 150 mg/day, respectively) and placebo were given, in a randomised, single-blind, crossover fashion for a period of 3 weeks each to 12 mild essential hypertensives. Power spectral analysis (short recordings) and noradrenaline measurements were also performed in the supine position and after a postural challenge (60 degrees head-up tilting test: HUT). The low-dose combination therapy induced the greatest reduction in LF component and in LF/HF ratio, both in the resting and tilted positions, as well as in blood pressure. However, the physiological autonomic response to HUT was maintained. Noradrenaline plasma levels were lower after the combined therapy than after each drug alone. Our data demonstrate that in mild and uncomplicated essential hypertension, the chronic low-dose combination therapy with an ACE-inhibitor and an AT(1)-antagonist is more effective than the recommended full-dose monotherapy with either drug in influencing the autonomic regulation of the heart, suggesting a relative reduction in sympathetic drive both at cardiac and systemic levels.

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation

PubMed Central

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong

2017-01-01

Background A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. Objective This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Methods Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Results Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil (p<0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. Conclusion A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL. PMID:28566902

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

PubMed

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong; Lee, Won-Soo

2017-06-01

A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil ( p <0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

Combination therapy strategies for improving PD-1 blockade efficacy: a new era in cancer immunotherapy.

PubMed

Chowdhury, P S; Chamoto, K; Honjo, T

2018-02-01

Programmed death 1 (PD-1) is an immune checkpoint molecule that negatively regulates T-cell immune function through the interaction with its ligand PD-L1. Blockage of this interaction unleashes the immune system to fight cancer. Immunotherapy using PD-1 blockade has led to a paradigm shift in the field of cancer drug discovery, owing to its durable effect against a wide variety of cancers with limited adverse effects. A brief history and development of PD-1 blockade, from the initial discovery of PD-1 to the recent clinical output of this therapy, have been summarized here. Despite its tremendous clinical success rate over other cancer treatments, PD-1 blockade has its own pitfall; a significant fraction of patients remains unresponsive to this therapy. The key to improve the PD-1 blockade therapy is the development of combination therapies. As this approach has garnered worldwide interest, here, we have summarized the recent trends in the development of PD-1 blockade-based combination therapies and the ongoing clinical trials. These include combinations with checkpoint inhibitors, radiation therapy, chemotherapy and several other existing cancer treatments. Importantly, FDA has approved PD-1 blockade agent to be used in combination with either CTLA-4 blockade or chemotherapy. Responsiveness to the PD-1 blockade therapy is affected by tumour and immune system-related factors. The role of the immune system, especially T cells, in determining the responsiveness has been poorly studied compared with those factors related to the tumour side. Energy metabolism has emerged as one of the important regulatory mechanisms for the function and differentiation of T cells. We have documented here the recent results regarding the augmentation of PD-1 blockade efficacy by augmenting mitochondrial energy metabolism of T cell. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Combination treatment with MEK and AKT inhibitors is more effective than each drug alone in human non-small cell lung cancer in vitro and in vivo.

PubMed

Meng, Jieru; Dai, Bingbing; Fang, Bingliang; Bekele, B Nebiyou; Bornmann, William G; Sun, Duoli; Peng, Zhenghong; Herbst, Roy S; Papadimitrakopoulou, Vassiliki; Minna, John D; Peyton, Michael; Roth, Jack A

2010-11-29

AZD6244 and MK2206 are targeted small-molecule drugs that inhibit MEK and AKT respectively. The efficacy of this combination in lung cancer is unknown. Our previous work showed the importance of activated AKT in mediating resistance of non-small cell lung cancer (NSCLC) to AZD6244. Thus we hypothesized that dual inhibition of both downstream MEK and AKT pathways would induce synergistic antitumor activity. In this study, we evaluated the efficacy of AZD6244 and MK2206 individually on a large panel of lung cancer cell lines. Then, we treated 28 human lung cancer cell lines with a combination of AZD6244 and MK2206 at clinically applicable drug molar ratios. The AZD6244-MK2206 combination therapy resulted in a synergistic effect on inhibition of lung cancer cell growth compared to the results of single drug treatment alone. MK2206 enhanced AZD6244-induced Bim overexpression and apoptosis in A549 and H157 cells. When we tested the combination of AZD6244 and MK2206 at ratios of 8∶1, 4∶1, 2∶1, and 1∶8, we found that the synergistic effect of the combination therapy was ratio-dependent. At ratios of 8∶1, 4∶1, and 2∶1, the drug combination consistently demonstrated synergy, whereas decreasing the ratio to 1∶8 resulted in a loss of synergy and produced an additive or antagonistic effect in most cell lines. Furthermore, the AZD6244-MK2206 combination therapy showed synergy in the suppression of A549 and H157 xenograft tumor growth and increased mean animal survival time. The AZD6244-MK2206 combination therapy resulted in effective inhibition of both p-ERK and p-AKT expression in tumor tissue. In addition, a significant increase of apoptosis was detected in tumor tissue from mice treated with AZD6244-MK2206 compared with that from the single agent treated mice. Our study suggests that the combination of AZD6244 and MK2206 has a significant synergistic effect on tumor growth in vitro and in vivo and leads to increased survival rates in mice bearing highly aggressive human lung tumors.

Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

PubMed Central

GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

2016-01-01

MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

PubMed Central

Parra, Karla; Valenzuela, Paloma; Lerma, Natzidielly; Gallegos, Alejandra; Reza, Luis C; Rodriguez, Georgialina; Emmenegger, Urban; Di Desidero, Teresa; Bocci, Guido; Felder, Mitchell S; Manciu, Marian; Kirken, Robert A; Francia, Giulio

2017-01-01

Background: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. Methods: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg−1 day−1), b) bolus (150 mg kg−1) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg−1 every 3 days). Results: EMT-6/P tumours responded to anti-CTLA-4 therapy, but this response was less effective when combined with bolus plus ldCTX. Anti-CTLA-4 could be effectively combined with either ldCTX (without a bolus), or with regimens of either sequential or concomitant gemcitabine, including in orthotopic EMT-6 tumours, and independently of the schedule of drug administration. Tumour responses were confirmed with CT-26 tumours but were less pronounced in drug-resistant EMT-6/CTX or EMT-6/DDP tumour models than in the parent tumour. A number of tumour bearing mice developed spontaneous metastases under continuous therapy. The majority of cured mice rejected tumour re-challenges. Conclusions: Metronomic CTX can be combined with anti-CTLA-4 therapy, but this therapy is impaired by concomitant bolus CTX. Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. PMID:28056464

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis.

PubMed

Kuriyama, Satoru; Otsuka, Yasushi; Ueda, Hiroyuki; Sugano, Naoki; Yoshizawa, Takeo; Yamada, Taku; Hosoya, Tatsuo

2011-02-01

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells.

PubMed

Nautiyal, Jyoti; Banerjee, Sanjeev; Kanwar, Shailender S; Yu, Yingjie; Patel, Bhaumik B; Sarkar, Fazlul H; Majumdar, Adhip P N

2011-02-15

Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF-1R as well as c-Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS-354825; Bristol-Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a nontoxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter, we utilized C57BL/6 APC(Min+/-) mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (i) colony formation, (ii) invasion through extracellular matrix and (iii) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT-116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in Apc(Min+/-) mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer. Copyright © 2010 UICC.

Curcumin Enhances Dasatinib Induced Inhibition of Growth and Transformation of Colon Cancer Cells

PubMed Central

Nautiyal, Jyoti; Banerjee, Sanjeev; Kanwar, Shailender S; Yu, Yingjie; Patel, Bhaumik B; Sarkar, Fazlul H; Majumdar, Adhip P. N.

2010-01-01

Colorectal cancer is the third most common form of malignancy, behind prostate and lung cancers. Despite recent advances in medicine, mortality from colorectal cancer remains high, highlighting the need for improved therapies. Numerous studies have demonstrated increased activation of EGFR and its family members (EGFRs), IGF-1R as well as c-Src in colorectal cancer. The current study was undertaken to examine the effectiveness of combination therapy of dasatinib (BMS-354825; Bristol-Myers Squibb), a highly specific inhibitor of Src family kinases (SFK) and a non-toxic dietary agent; curcumin (diferuloylmethane), in colorectal cancer in in vitro and in vivo experimental models. For the latter we utilized C57BL/6J-ApcMin+/− mice. Initial in vitro studies revealed synergistic interactions between the two agents. Additionally, we have observed that combination treatment causes a much greater inhibition of the following metastatic processes than either agent alone: (a) colony formation (b) invasion through extracellular matrix (c) tubule formation by endothelial cells. Dasatinib affects the cell adhesion phenotype of colon cancer HCT-116 cells whereas the combination therapy enhances this effect to a greater extent. Preclinical investigation revealed that the combination therapy to be highly effective causing an over 95% regression of intestinal adenomas in ApcMin+/− mice, which could be attributed to decreased proliferation and increased apoptosis. In conclusion, our data suggest that combination treatment of dasatinib and curcumin could be a potential therapeutic strategy for colorectal cancer. PMID:20473900

Combinational chelation therapy abrogates lead-induced neurodegeneration in rats.

PubMed

Pachauri, Vidhu; Saxena, Geetu; Mehta, Ashish; Mishra, Deepshikha; Flora, Swaran J S

2009-10-15

Lead, a ubiquitous and potent neurotoxicant causes oxidative stress which leads to numerous neurobehavioral and physiological alterations. The ability of lead to bind sulfhydryl groups or compete with calcium could be one of the reasons for its debilitating effects. In the present study, we addressed: i) if chelation therapy could circumvent the altered oxidative stress and prevent neuronal apoptosis in chronic lead-intoxicated rats, ii) whether chelation therapy could reverse biochemical and behavioral changes, and iii) if mono or combinational therapy with captopril (an antioxidant) and thiol chelating agents (DMSA/MiADMSA) is more effective than individual thiol chelator in lead-exposed rats. Results indicated that lead caused a significant increase in reactive oxygen species, nitric oxide, and intracellular free calcium levels along with altered behavioral abnormalities in locomotor activity, exploratory behavior, learning, and memory that were supported by changes in neurotransmitter levels. A fall in membrane potential, release of cytochrome c, and DNA damage indicated mitochondrial-dependent apoptosis. Most of these alterations showed significant recovery following combined therapy with captopril with MiADMSA and to a smaller extend with captopril+DMSA over monotherapy with these chelators. It could be concluded from our present results that co-administration of a potent antioxidant (like captopril) might be a better treatment protocol than monotherapy to counter lead-induced oxidative stress. The major highlight of the work is an interesting experimental evidence of the efficacy of combinational therapy using an antioxidant with a thiol chelator in reversing neurological dystrophy caused due to chronic lead exposure in rats.

[The results of the combined application of extracorporeal shock-wave therapy and radon baths during the rehabilitative treatment of the patients presenting with gonarthrosis].

PubMed

Razumov, A N; Puriga, A O; Yurova, O V

2015-01-01

Osteoarthritis (OA) is one of the leading diseases of the musculoskeletal system and the main cause of arthritic joint damage. The objective of the present study was to evaluate the effectiveness of the combined application of radon baths and shock-wave therapy in the patients suffering from knee OA. The study involved 75 patients at the age of 35 to 62 years with the confirmed diagnosis of stage II and III gonarthrosis; they were divided into 3 groups. The patients of the main group received the combined treatment including extracorporeal shock-wave therapy and radon baths The patients comprising the group of comparison were given the course of radon therapy alone while those in the control group were offered the standard treatment including physiotherapy, magnetic therapy, and NSAIDs. The study has demonstrated the high effectiveness of the combined application of the radon baths and extracorporeal shock-wave therapy for the rehabilitation of the patients with deforming arthrosis of the knee that was apparent from the substantial decrease of pain syndrome, the increase of the range of motions in the knee joints, and the overall improvement of the quality of life. These beneficial changes persisted for a period of up to 6 months. The results of the present study give reason to recommend the proposed method of the remedial treatment for the wide practical application as a component in the framework of the medical rehabilitation programs.

Quantitative model for the blood pressure-lowering interaction of valsartan and amlodipine.

PubMed

Heo, Young-A; Holford, Nick; Kim, Yukyung; Son, Mijeong; Park, Kyungsoo

2016-12-01

The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. A two-compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D 1  + D 2 ) +ALPHA×(D 1 × D 2 ). D 1 and D 2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were -0.171 (95% CI: -0.218, -0.143) for SBP and -0.0312 (95% CI: -0.07739, -0.00283) for DBP. These infra-additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra-additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. © 2016 The British Pharmacological Society.

Quantitative model for the blood pressure‐lowering interaction of valsartan and amlodipine

PubMed Central

Heo, Young‐A; Holford, Nick; Kim, Yukyung; Son, Mijeong

2016-01-01

Aims The objective of this study was to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model to quantitatively describe the antihypertensive effect of combined therapy with amlodipine and valsartan. Methods PK modelling was used with data collected from 48 healthy volunteers receiving a single dose of combined formulation of 10 mg amlodipine and 160 mg valsartan. Systolic (SBP) and diastolic blood pressure (DBP) were recorded during combined administration. SBP and DBP data for each drug alone were gathered from the literature. PKPD models of each drug and for combined administration were built with NONMEM 7.3. Results A two‐compartment model with zero order absorption best described the PK data of both drugs. Amlodipine and valsartan monotherapy effects on SBP and DBP were best described by an I max model with an effect compartment delay. Combined therapy was described using a proportional interaction term as follows: (D1 + D2) +ALPHA×(D1 × D2). D1 and D2 are the predicted drug effects of amlodipine and valsartan monotherapy respectively. ALPHA is the interaction term for combined therapy. Quantitative estimates of ALPHA were −0.171 (95% CI: −0.218, −0.143) for SBP and −0.0312 (95% CI: −0.07739, −0.00283) for DBP. These infra‐additive interaction terms for both SBP and DBP were consistent with literature results for combined administration of drugs in these classes. Conclusion PKPD models for SBP and DBP successfully described the time course of the antihypertensive effects of amlodipine and valsartan. An infra‐additive interaction between amlodipine and valsartan when used in combined administration was confirmed and quantified. PMID:27504853

Cooperative effect between immunotherapy and antiangiogenic therapy leads to effective tumor rejection in tolerant Her-2/neu mice.

PubMed

Cuadros, Camilo; Dominguez, Ana Lucia; Frost, Gregory I; Borgstrom, Per; Lustgarten, Joseph

2003-09-15

Immunotherapy is an attractive strategy for cancer treatment. However, self-tolerance is one of the major mechanisms that dampen immune responses against self-tumor antigens. We have demonstrated that Her-2/neu transgenic mice (neu mice) are tolerant to neu antigens and contain only a low avidity repertoire for neu. However, this repertoire has antitumor activity. Immunizations of neu mice are capable of activating the low-avidity T cells that, at best, retard the tumor growth. To increase the efficacy of the antitumor responses in neu mice, we hypothesized that immunotherapy in combination with antiangiogenic therapy would be a more efficient strategy for tumor eradication. The rationale for using this combination was that by decreasing the growth rate of the tumor with an antiangiogenic therapy, the low-avidity repertoire of neu mice stimulated by immunotherapeutic intervention would be more effective in destroying the slow growing tumor. To test this hypothesis, we stably expressed a soluble form of the Flt-1 vascular endothelial growth factor receptor (sFlt-1) on N202.1A cells, using a retrovirus vector. Expression of sFlt-1 on N202.1A (N202-Flt) cells significantly inhibited the tumor growth compared with N202.1A parental cells. In contrast to the application of immunotherapy alone or antiangiogenic therapy alone, which delayed the tumor growth, the combination of the two therapies provided complete inhibition of tumor growth in Her-2/neu mice. These results indicate that the use of tumor targeting with immunotherapy in simultaneous combination with antiangiogenic therapy provides a more efficient strategy for the treatment of solid tumors.

[Electrical stimulation therapy and its effects on the general activity of motor impaired cerebral palsied children; a comparative study of the Bobath physiotherapy and its combination with the Hufschmidt electrical stimulation therapy (author's transl)].

PubMed

Leyendecker, C

1975-08-01

The purpose of this study was to answer the following questions: (1) Is it more effective to treat spastic cerebral palsy with the Hufschmidt electrical stimulation therapy combined with the Bobath neuro-development treatment or only with the Bobath therapy? (2) Can a general increase in activity be obtained by the electrotherapeutic muscle stimulation? A test group (combined Hufschmidt/Bobath therapy) and a control group (Bobath), both consisting of 10 subjects, were observed for four months. The duration of observation was divided into two four months treatment periods with a rest interval of two months in between. At the start of therapeutic measures, motor activity and psychic condition were tested with corresponding motormetric and psychodiagnostic techniques; three check-up examinations were carried out at the end of the first, and at the beginning and end of the second period of treatment. The motor-metric control examination showed that at the end of the first period the test group had achieved by far the better results, but at the end of the second therapeutic period, both groups were equally successful. The combined electrophysiotherapy hence reached in a relatively shorter time - as it were by leaps and bounds - the optimal obtainable state of functional improvements which, with the Bobath therapy alone, can be effected more slowly but with more continuity. The psychodiagnostic controls clearly indicate that the electrical stimulation produced an unspecified increase in activity, especially after the first phase of treatment, whereas in the second phase this could only be proven in a graded form. The report closes with an examination of the results and their consequences for the implementation of the treatment for cerebral palsied children.

Metabolic and hypoxic adaptation to anti-angiogenic therapy: a target for induced essentiality

PubMed Central

McIntyre, Alan; Harris, Adrian L

2015-01-01

Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6–8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. PMID:25700172

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro

PubMed Central

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-01-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ-rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ-rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ-rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ-ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma. PMID:27840931

Combined antitumor activity of the nitroreductase/CB1954 suicide gene system and γ-rays in HeLa cells in vitro.

PubMed

Teng, Geling; Ju, Yuanrong; Yang, Yepeng; Hua, Hu; Chi, Jingyu; Mu, Xiuan

2016-12-01

Escherichia coli nitroreductase (NTR) may convert the prodrug CB1954 (5-(aziridin-1-yl)-2,4-dinitrobenzamide) into a bifunctional alkylating agent, which may lead to DNA crosslinks and the apoptosis of cancer cells. NTR/CB1954 has been demonstrated to be an effective gene therapy in cancer cells. The present study examined whether the NTR/CB1954 suicide gene system had cytotoxic effects on HeLa cells and may improve the radiosensitivity of HeLa cells to γ‑rays. It was observed that the NTR/CB1954 suicide gene system exerted marked cytotoxic effects on HeLa cells. The combined therapeutic effects of NTR/CB1954 and γ‑rays on HeLa cells demonstrated a synergistic effect. CB1954 at concentrations of 12.5 and 25 µmol/l increased the sensitization enhancement ratio of HeLa cells to 1.54 and 1.66, respectively. Therefore, when compared with monotherapy, the combined therapy of NTR/CB1954 and γ‑rays may increase the apoptotic rate and enhance the radiosensitivity of HeLa cells. The combined therapy of γ‑ray radiation and the NTR/CB1954 suicide gene system may be a novel and potent therapeutic method for the treatment of cervical carcinoma.

Combination chemotherapy increases cytotoxicity of multiple myeloma cells by modification of nuclear factor (NF)-κB activity

PubMed Central

Salem, Kelley; Brown, Charles O.; Schibler, Jeanine; Goel, Apollina

2012-01-01

The NF-κB signaling pathway is critical in myeloma cell proliferation, inhibition of apoptosis, and emergence of therapy resistance. The chemotherapeutic drugs, dexamethasone (Dex) and bortezomib (BTZ), are widely used in clinical protocols for multiple myeloma (MM) and inhibit the NF-κB signaling pathway by distinct mechanisms. This study evaluates the efficacy of combination therapy with Dex and BTZ and investigates the mechanistic underpinning of endogenous and therapy-induced NF-κB activation in MM. Human myeloma cells and bone marrow stromal cells (BMSCs) were used in monocultures and co-cultures to determine the cytotoxic effects of Dex and/or BTZ. Our results show that combined treatment of Dex with BTZ enhanced direct apoptosis of drug-sensitive and drug-resistant myeloma cells. In the presence of BMSCs, Dex plus BTZ combination inhibited ionizing radiation (IR)-induced interleukin (IL)-6 secretion from BMSCs and induced myeloma cytotoxicity. Mechanistically, Dex treatment increased IκBα protein and mRNA expression and compensated for BTZ-induced IκBα degradation. Dex plus BTZ combination inhibited basal and therapy-induced NF-κB activity with cytotoxicity in myeloma cells resistant to BTZ. Furthermore, combination therapy down-regulated the NF-κB targeted gene expression of IL-6 and manganese superoxide dismutase (MnSOD), which can induce chemo- and radio-resistance in MM. This study provides mechanistic rationale for combining the NF-κB-targeting drugs Dex and BTZ in myeloma therapy and supports potential combinations of these drugs with radiotherapy and additional chemotherapeutic drugs, for clinical benefit in MM. PMID:23063726

Antimicrobial Photodynamic Therapy Combined With Conventional Endodontic Treatment to Eliminate Root Canal Biofilm Infection

PubMed Central

Garcez, Aguinaldo S.; Ribeiro, Martha S.; Tegos, George P.; Núñez, Silvia C.; Jorge, Antonio O.C.; Hamblin, Michael R.

2011-01-01

Background and Objective To compare the effectiveness of antimicrobial photodynamic therapy (PDT), standard endodontic treatment and the combined treatment to eliminate bacterial biofilms present in infected root canals. Study Design/Materials and Methods Ten single-rooted freshly extracted human teeth were inoculated with stable bioluminescent Gram-negative bacteria, Proteus mirabilis and Pseudomonas aeruginosa to form 3-day biofilms in prepared root canals. Bioluminescence imaging was used to serially quantify bacterial burdens. PDT employed a conjugate between polyethylenimine and chlorin(e6) as the photosensitizer (PS) and 660-nm diode laser light delivered into the root canal via a 200-µ fiber, and this was compared and combined with standard endodontic treatment using mechanical debridement and antiseptic irrigation. Results Endodontic therapy alone reduced bacterial bioluminescence by 90% while PDT alone reduced bioluminescence by 95%. The combination reduced bioluminescence by >98%, and importantly the bacterial regrowth observed 24 hours after treatment was much less for the combination (P<0.0005) than for either single treatment. Conclusions Bioluminescence imaging is an efficient way to monitor endodontic therapy. Antimicrobial PDT may have a role to play in optimized endodontic therapy. PMID:17066481

Gene Therapy Targeting Glaucoma: Where Are We?

PubMed Central

Liu, Xuyang; Rasmussen, Carol A.; Gabelt, B’Ann T.; Brandt, Curtis R.; Kaufman, Paul L.

2010-01-01

In a chronic disease such as glaucoma, a therapy that provides a long lasting local effect, with minimal systemic side effects, while circumventing the issue of patient compliance, is very attractive. The field of gene therapy is growing rapidly and ocular applications are expanding. Our understanding of the molecular pathogenesis of glaucoma is leading to greater specificity in ocular tissue targeting. Improvements in gene delivery techniques, refinement of vector construction methods, and development of better animal models combine to bring this potential therapy closer to reality. PMID:19539835

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study

PubMed Central

Yang, Rui-Qi; Mao, Hua; Huang, Li-Yun; Su, Pei-Zhu; Lu, Min

2017-01-01

AIM To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-β1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group (P < 0.05). There were significant differences (P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-β1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group (P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group (P < 0.05). CONCLUSION Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa. PMID:28275307

Oral contraceptive therapy for polycystic ovary disease after chronic gonadotropin-releasing agonist administration. Predictors of continued ovarian suppression.

PubMed

Elkind-Hirsch, K E; Anania, C; Malinak, R

1996-09-01

To study the beneficial effects of oral contraceptive (OC) therapy following gonadotropin-releasing hormone agonist (GnRH-a) administration in women with polycystic ovary disease (PCOD). Twenty-three hyperandrogenic women (aged 15-39) were randomized into two groups; GnRH-a (depot every 28 days) for six months or combination therapy (GnRH-a plus OC "addback") for six months. Following six months of treatment with either therapy, all patients received OC therapy for at least six months. The hormonal state was evaluated at three-month intervals. Hormone levels of luteinizing hormone (LH), testosterone (T) and free T remained suppressed within the normal range in 11 of 17 patients (65%) during the six months of OC only therapy, while the other six patients showed "escape" from suppression, with the LH, T and free T concentrations rising to pre-GnRH-a treatment levels. Use of OC addback therapy did not potentiate the long-acting therapeutic effect of GnRH-a pretreatment; three of six patients in the escape group were pretreated with combination therapy and three with GnRH-a only. In the majority of women with PCOD, OC therapy following GnRH-a administration was effective in maintaining ovarian androgen suppression. Failure to maintain ovarian suppression in this patient population was associated with higher elevations of baseline free T concentrations.

Case Report: A Non-small Cell Lung Cancer Patient Treated with GcMAF, Sonodynamic Therapy and Tumor Treating Fields.

PubMed

Inui, Toshio; Amitani, Haruka; Kubo, Kentaro; Kuchiike, Daisuke; Uto, Yoshihiro; Nishikata, Takahito; Mette, Martin

2016-07-01

Macrophage activating factor (MAF)-based immunotherapy has a wide application for use in treating many diseases via macrophage activation. Sonodynamic therapy (SDT) using low-intensity ultrasound and tumor treating field (TTF) therapy are novel therapeutic modalities. SDT is usually combined with ozone therapy to improve local hypoxia within the tumor environment. We treated a 77-year-old male diagnosed with non-small cell lung cancer ((NSCLC) stage 3B) using second-generation serum GcMAF and oral colostrum MAF-based immunotherapy combined with SDT, TTF and ozone therapies. This case report demonstrates that GcMAF, oral colostrum MAF, SDT, TTF and ozone therapy can be used for NSCLC without adverse effects. This case report suggests a new concept of cancer treatment using local destruction of cancer tissue, in this case conducted with SDT and TTF therapy, to be used in combination with serum GcMAF and colostrum MAF immunotherapy as a systemic treatment. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

HSA/PSS coated gold nanorods as thermo-triggered drug delivery vehicles for combined cancer photothermal therapy and chemotherapy

NASA Astrophysics Data System (ADS)

Tu, Ting-Yu; Yang, Shu-Jyuan; Wang, Chung-Hao; Lee, Shin-Yu; Shieh, Ming-Jium

2018-02-01

Drug delivery systems combined multimodal therapy strategies are very promising in cancer theranostic applications. In this work, a new drug-delivery vehicles based on human serum albumin (HSA)-coated gold nanorods (GNR/PSS/HSA NPs) was developed. The success of coating was verified by transmission electron microscopy (TEM), zeta potential and fourier transform infrared spectroscopy (FTIR). Furthermore, it is demonstrated that doxorubicin (DOX) is successfully loaded among multilayered gold nanorods by the electrostatic and hydrophobic force, and DOX@GNR/PSS/HSA NPs were highly biocompatible and stable in various physiological solutions. The NPs possess strong absorbance in nearinfrared (NIR) region, and high photothermal conversion efficiency for outstanding photothermal therapy applications. A bimodal drug release triggered by proteinase or NIR irradiation has been revealed, resulting in a significant chemotherapeutic effect in tumor sites because of the preferential drug accumulation and triggered release. Importantly, the in vitro and in vivo experiments demonstrated that DOX@GNR/PSS/HSA NPs, which combined photothermal and chemotherapy for cancer therapy, revealing a remarkably superior synergistic anticancer effect over either monotherapy. All these results suggested a considerable potential of DOX@GNR/PSS/HSA NPs nano-platform for antitumor therapy.

Economic evaluation of empirical antisecretory therapy versus Helicobacter pylori test for management of dyspepsia: a randomized trial in primary care.

PubMed

Jarbol, Dorte Ejg; Bech, Mickael; Kragstrup, Jakob; Havelund, Troels; Schaffalitzky de Muckadell, Ove B

2006-01-01

An economic evaluation was performed of empirical antisecretory therapy versus test for Helicobacter pylori in the management of dyspepsia patients presenting in primary care. A randomized trial in 106 general practices in the County of Funen, Denmark, was designed to include prospective collection of clinical outcome measures and resource utilization data. Dyspepsia patients (n = 722) presenting in general practice with more than 2 weeks of epigastric pain or discomfort were managed according to one of three initial management strategies: (i) empirical antisecretory therapy, (ii) testing for Helicobacter pylori, or (iii) empirical antisecretory therapy, followed by Helicobacter pylori testing if symptoms improved. Cost-effectiveness and incremental cost-effectiveness ratios of the strategies were determined. The mean proportion of days without dyspeptic symptoms during the 1-year follow-up was 0.59 in the group treated with empirical antisecretory therapy, 0.57 in the H. pylori test-and-eradicate group, and 0.53 in the combination group. After 1 year, 23 percent, 26 percent, and 22 percent, respectively, were symptom-free. Applying the proportion of days without dyspeptic symptoms, the cost-effectiveness for empirical treatment, H. pylori test and the combination were 12,131 Danish kroner (DKK), 9,576 DKK, and 7,301 DKK, respectively. The incremental cost-effectiveness going from the combination strategy to empirical antisecretory treatment or H. pylori test alone was 54,783 DKK and 39,700 DKK per additional proportion of days without dyspeptic symptoms. Empirical antisecretory therapy confers a small insignificant benefit but costs more than strategies based on test for H. pylori and is probably not a cost-effective strategy for the management of dyspepsia in primary care.

Myofunctional therapy improves adherence to continuous positive airway pressure treatment.

PubMed

Diaféria, Giovana; Santos-Silva, Rogerio; Truksinas, Eveli; Haddad, Fernanda L M; Santos, Renata; Bommarito, Silvana; Gregório, Luiz C; Tufik, Sergio; Bittencourt, Lia

2017-05-01

Few studies have investigated myofunctional therapy in patients with obstructive sleep apnea syndrome (OSAS). The objective of this study was to evaluate the effect of myofunctional therapy on continuous positive airway pressure (CPAP) adherence. The study was registered at ClinicalTrials.gov (NCT01289405). Male patients with OSAS were randomly divided into four treatment groups: placebo, patients undergoing placebo myofunctional therapy (N = 24); myofunctional therapy, undergoing myofunctional therapy (N = 27); CPAP, undergoing treatment with CPAP (N = 27); and combined, undergoing CPAP therapy and myofunctional therapy (N = 22). All patients underwent evaluations before and after 3 months of treatment evaluation and after 3 weeks of washout. Evaluations included Epworth sleepiness scale (ESS), polysomnography, and myofunctional evaluation. The 100 men had a mean age of 48.1 ± 11.2 years, body mass index of 27.4 ± 4.9 kg/m 2 , ESS score of 12.7 ± 3.0, and apnea-hypopnea index (AHI) of 30.9 ± 20.6. All treated groups (myofunctional therapy, CPAP, and combined myofunctional therapy with CPAP) showed decreased ESS and snoring, and the myofunctional therapy group maintained this improvement after the "washout" period. AHI reduction occurred in all treated groups and was more significant in CPAP group. The myofunctional therapy and combined groups showed improvement in tongue and soft palate muscle strength when compared with the placebo group. The association of myofunctional therapy to CPAP (combined group) showed an increased adherence to CPAP compared with the CPAP group. Our results suggest that in patients with OSAS, myofunctional therapy may be considered as an adjuvant treatment and an intervention strategy to support adherence to CPAP.

The Effect of Methadone-Maintenance Therapy With and Without Interactive Treatment on Improving Emotion-Regulation Strategies and Resilience Among Opiate-Dependent Clients

PubMed Central

Hoseiny, Hadis; Jadidi, Mohsen; Habiballah Nataj, Leila; Saberi- Zafarghandi, Mohammad Bagher

2015-01-01

Background: Due to the chronic and recurrent nature of addiction, many people who quit drug addiction may slip back into the pattern of using drugs shortly after the detoxification period. Emotion-regulation strategies and resilience play an important role in preventing the recurrences of substance abuse. Objectives: This study aimed to compare the effects of methadone-maintenance therapy (MMT) and interactive therapy (a combination of MMT and cognitive-behavioral therapy) on improving emotion-regulation strategies and resilience among opiate-dependent clients. Patients and Methods: This pretest-posttest quasi-experimental study was performed on 60 patients with substance abuse admitted to Methadone Addiction Treatment Centers and Detox Centers in Sari within three months of therapy for their addiction (from October to December 2013). Then, the participants were randomly assigned to two different groups (n = 30) were examined in two groups of 30 people targeted to be available in the selected population. Participants in all three groups, before and after the intervention, filled out the questionnaires of Schutte emotional intelligence scale and Connor-Davidson resiliency questionnaire. Data were analyzed using the analysis of covariance method. Results: The results showed that an interactive therapy would be significantly more effective than the MMT on improving emotion-regulation strategies and promoting the resilience level among opiate-dependent clients. Moreover, the results showed that cognitive- behavior therapy combined with MMT may improve emotion-regulation strategies, and promote the amount of resiliency and recovery. Conclusions: The cognitive-behavior therapy combined with MMT can improve emotion-regulation strategies and resiliency and thus prevent the substance-abuse relapse. PMID:25821751

Minimal invasive treatments for liver malignancies.

PubMed

Orsi, Franco; Varano, Gianluca

2015-11-01

Minimal invasive therapies have proved useful in the management of primary and secondary hepatic malignancies. The most relevant aspects of all these therapies are their minimal toxicity profiles and highly effective tumor responses without affecting the normal hepatic parenchyma. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option for patients who previously may have had few alternatives. Combination of these therapies might extend indications to bring curative treatment to a wider selected population. The results of various ongoing combination trials of intraarterial therapies with targeted therapies are awaited to further improve survival in this patient group. This review focuses on the application of ablative and intra-arterial therapies in the management of hepatocellular carcinoma and hepatic colorectal metastasis. Copyright © 2015 Elsevier B.V. All rights reserved.

Risks and safety of combination therapy for hypothyroidism.

PubMed

Jonklaas, Jacqueline

2016-08-01

Hypothyroidism is currently a condition that can be treated, but not cured. Although levothyroxine reverses stigmata of hypothyroidism in most individuals, some patients feel dissatisfied with 'monotherapy', and this has stimulated interest in 'combination therapy' with both levothyroxine and liothyronine. A search of PubMed was conducted using terms including hypothyroidism, treatment, benefits, risks, and safety. Based on the articles identified, the body of evidence regarding the efficacy of traditional levothyroxine is reviewed. Concerns with levothyroxine therapy including impaired quality of life in treated patients, thyroxine-predominant hormone ratios, and inadvertent iatrogenic thyroid disease are discussed. The trials of combination therapy performed since 1999 were reviewed. The heterogeneity of these trials, both in terms of design and results, is discussed. The potential for new trials to determine whether combination therapy can reverse the dissatisfaction associated with monotherapy, while avoiding non-physiologic hormone ratios, inadvertent thyrotoxicosis, and unacceptable side effects is discussed. Expert commentary: Research regarding which therapy fully reverses hypothyroidism at a tissue and cellular level is ongoing. The field would be advanced by the development of an extended release preparation of liothyronine. In the future regeneration of functional thyroid follicles from stem cells may offer hope for curing hypothyroidism.

Aspirin and proton pump inhibitor combination therapy for prevention of cardiovascular disease and Barrett's esophagus.

PubMed

Peura, David A; Wilcox, C Mel

2014-01-01

Aspirin, used at low doses (75-325 mg daily), prevents aggregation of platelets and is prescribed for patients as pharmacologic prevention of cardiovascular disease. Despite the well-documented beneficial effects of aspirin, prolonged use is associated with damage to the gastrointestinal (GI) mucosa in the upper and lower GI tract. Patient risk of hemorrhage and peptic ulcer formation is increased with older age, previous ulcer history, Helicobacter pylori infection, and concomitant use of nonsteroidal anti-inflammatory drugs, corticosteroids, or antithrombotic agents. As termination of aspirin therapy can precipitate a cardiovascular event, patients at risk need co-therapy with gastroprotective agents, such as proton pump inhibitors (PPIs), to reduce the GI side effects of aspirin treatment. Fixed-dose combinations of low-dose aspirin and gastroprotective agents have been designed to increase medication compliance, improve clinical outcomes, and reduce the overall cost of therapy. Prolonged use of PPIs may, however, lead to serious adverse effects or, in some cases, reduce the cardioprotective effects of aspirin. Hence, physicians need to carefully consider the benefits and risks associated with the condition of each patient to optimize clinical outcomes of combination therapy. A growing body of clinical evidence indicates that aspirin may decrease the risk of colorectal and other GI cancers, as well as reduce progression from Barrett's esophagus (BE) to esophageal adenocarcinoma. Furthermore, PPIs have recently been shown to reduce neoplastic transformation in patients with BE. Thus, the use of a fixed-dose aspirin/PPI combination could potentially provide chemopreventive benefit to patients with BE, and, at the same time, treat the underlying gastroesophageal reflux responsible for the condition.

Hemodynamic effects of renin-angiotensin-aldosterone inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for portal hypertension in cirrhosis: A meta-analysis

PubMed Central

Wang, Jianrong; Lu, Wenxia; Li, Jingjing; Zhang, Rong; Zhou, Yuqing; Yin, Qin; Zheng, Yuanyuan; Wang, Fan; Xia, Yujing; Chen, Kan; Li, Sainan; Liu, Tong; Lu, Jie; Zhou, Yingqun; Guo, Chuan-Yong

2017-01-01

β-blockers are commonly used for the treatment of acute variceal bleeding in cirrhosis. Renin-angiotensin-aldosterone antagonists (angiotensin I-converting enzyme inhibitors, angiotensin receptor blockers and aldosterone antagonists) are potential therapies for portal hypertension. Several studies have compared the renin-angiotensin-aldosterone system (RAAS) inhibitor and β-blocker combination therapy vs. β-blocker monotherapy, with inconsistent results. The aim of the present study was to assess the efficacy of the RAAS inhibitor and β-blocker combination therapy vs. β-blocker monotherapy for hepatic vein pressure gradient (HVPG) reduction in cirrhosis. Studies were obtained using PubMed, Embase, Medline and Cochrane library databases up to July 2015, and the weighted mean difference (WMD) in HVPG reduction was used as a measure of treatment efficacy. In total, three studies (91 patients) were included. When compared to the β-blocker monotherapy, the RAAS inhibitor and β-blocker combination therapy resulted in a significant HVPG reduction [WMD 1.70; 95% confidence interval (CI): 0.52–2.88]. However, there was no significant difference in the heart rate reduction between the monotherapy and combination therapy groups (WMD −0.11; 95% CI: −3.51–3.29). In addition, no significant difference in the hemodynamic response was observed between the two groups (WMD 1.46; 95% CI: 0.93–2.30). In conclusion, the RAAS inhibitor and β-blocker combination therapy reduces portal hypertension significantly and to a greater extent than β-blocker monotherapy. Both therapies reduced the heart rate to similar levels; however, the RAAS inhibitor and β-blocker combination therapy reduced the mean arterial pressure to a greater extent. Due to the limited number of studies included, the data available do not allow a satisfactory comparison of adverse events. Moreover, further larger-scale trials are required in order to strengthen the results of the present study. PMID:28565796

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

[Nonspecific symptoms of pain syndromes of cervicobrachial localization and their dynamics under the influence of non - pharmacological treatment].

PubMed

Ярошевський, Олександр Анатолійович

2016-01-01

The relevance of this study is caused by the wide spread of musculoskeletal pain, particularly among young people of working age and lack of effectiveness of drug treatment. To study the capability of non-pharmacological treatment in patients with myofascial pain syndrome of cervicobrachial localization considering the influence to nonspecific symptoms of myofascial pain syndrome (autonomic dysfunctions and emotional disorders). We studied 115 patients aged from 18 to 44 years with myofascial pain syndrome of cervicobrachial localization. We used neurological, vertebral- neurological, neuropsychological examination. The severity of pain was assessed by the Visual analog scale for pain (VAS pain). Patients were divided into two groups. The first group of patients (59 individuals) received the complex of manual therapy. The second group of patients (56 individuals) received the complex of manual therapy combined with acupuncture. Non-pharmacological treatment was effective in patients with myofascial pain syndrome of cervicobrachial localization. Application of manual therapy methods in the treatment of myofascial pain syndrome of cervicobrachial localization leading to the reduction of severity of pain, emotional disorders and autonomic dysfunctions. The combination of manual therapy with acupuncture increases the effectiveness of treatment of myofascial pain syndrome of cervicobrachial localization by reducing the emotional disorders and autonomic dysfunctions. Patients with myofascial pain syndrome of cervicobrachial localization need the complex of manual therapy combined with acupuncture. The manual therapy corrects abnormal biomechanical pattern while acupuncture corrects autonomic dysfunctions and emotional disorders.

A controlled study of agoraphobia and the independent effect of virtual reality exposure therapy.

PubMed

Malbos, Eric; Rapee, Ronald M; Kavakli, Manolya

2013-02-01

Past controlled clinical trials centred on virtual reality exposure therapy (VRET) for agoraphobia mostly used multicomponent therapy with success. However, the present paper aimed to evaluate the independent effect of VRET for agoraphobia. A controlled study involving 18 agoraphobic participants assigned to two groups: VRET only and VRET with cognitive therapy. Nine specific virtual environments were developed using an affordable game level editor. Questionnaires, behavioural tests and physiological measures indicated a positive effect of VRET. Correlations supported the predictive value of presence towards treatment outcome. The addition of cognitive therapy did not provide significant additional benefit. Overall, the isolated effects of VRET did not seem to be significantly less than the effects of VRET combined with cognitive therapy. Future research should explore the use of other components in addition to cognitive therapy and VRET for agoraphobia as well as its possible use in patients' homes.

[Combined palliative hypofractionated radiation and carboplatin chemotherapy of intranasal tumours in dogs].

PubMed

Schwietzer, A; Kessler, M; Kandel-Tschiederer, B

2012-10-17

Combination therapy of intranasal tumours in dogs with palliative 60 cobalt radiation and carboplatin chemotherapy. Twenty-five dogs with intranasal tumours were treated in the Hofheim Veterinary Hospital (Germany) from 2004 to 2006 with a total radiation dose of 24Gy (3 fractions of 8 Gy on days 0, 7 and 21) and five doses of Carboplatin (270-300 mg/m² BSA i.v. every 21-28 days). In 88% patients, clinical symptoms subsided partially or completely resulting in improvement in quality of life. Computed tomography revealed partial (5/25) or complete (5/25) tumour remissions. Chemotherapy was well tolerated. Radiation therapy caused no or minimal side effects except for 3 dogs (12%), which experienced serious ocular side effects resulting in loss of vision of the affected eye and one dog with epileptic seizures. Survival times ranged from 10-639 days with a median of 156 days. There was no statistically significant correlation between the parameters breed, age, sex, brain invasion or tumour stage and survival time or progression free interval. Survival time and progression free interval were significantly correlated with the degree of tumour remission. It can be concluded from this study that palliative radiation therapy combined with chemotherapy results in excellent palliation of clinical symptoms and acceptable survival times. There was no advantage of combined therapy (radiation with carboplatin) when compared to literature data on results of radiation therapy alone.

Combination photodynamic therapy of human breast cancer using salicylic acid and methylene blue

NASA Astrophysics Data System (ADS)

Hosseinzadeh, Reza; Khorsandi, Khatereh; Jahanshiri, Maryam

2017-09-01

The objective of this study was to evaluate the effects of combination therapy with methylene blue (MB) assisted photodynamic therapy (PDT) and salicylic acid (SA) as chemo-therapy anticancer agent. The binding of salicylic acid to methylene blue was studied using spectrophotometric method. The results show the 1:2 complex formation between SA and MB. The binding constants and related Gibbs free energies o are obtained (Kb1 = 183.74, Kb2 = 38.13 and ∆ Gb1° = 12.92 kJ·mol- 1, ∆ Gb2° =9.02 kJ·mol- 1). The spectrophotometric results show the improvement in solubilization and reduction prevention for SA and MB in the complex form. These results are in agreements with cellular experiments. The dark toxicity measurements represent the improve efficacy of chemotherapy using combination of SA and MB. The photodynamic therapy results (using red LED as light source (630 nm; power density: 30 mW cm- 2)) show that the cancer cell killing efficiency of MB increases in the combination with SA due to reduction prevention and stabilization of monomeric form of MB.

Prospective, randomized comparison between pulsatile GnRH therapy and combined gonadotropin (FSH+LH) treatment for ovulation induction in women with hypothalamic amenorrhea and underlying polycystic ovary syndrome.

PubMed

Dubourdieu, Sophie; Fréour, Thomas; Dessolle, Lionel; Barrière, Paul

2013-05-01

To compare the efficacy of pulsatile GnRH therapy versus combined gonadotropins for ovulation induction in women with both hypothalamic amenorrhoea and polycystic ovarian syndrome (HA/PCOS) according to their current hypothalamic status. This single-centre, prospective, randomized study was conducted in the Nantes University Hospital, France. Thirty consecutive patients were treated for ovulation induction with either pulsatile GnRH therapy or combined gonadotropins (rFSH+rLH). Frequency of adequate ovarian response (mono- or bi-follicular) and clinical pregnancy rate were then compared between both groups. Ovarian response was similar in both groups with comparable frequency of adequate ovarian response (73% vs 60%), but the clinical pregnancy rate was significantly higher in the pulsatile GnRH therapy group than in the combined gonadotropin group (46% vs 0%). HA/PCOS is a specific subgroup of infertile women. Pulsatile GnRH therapy is an effective and safe method of ovulation induction that can be used successfully in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of omega-3 polyunsaturated fatty acids and aspirin, alone and combined, on canine platelet function.

PubMed

Westgarth, S; Blois, S L; D Wood, R; Verbrugghe, A; Ma, D W

2018-05-01

To compare haemostatic function in healthy dogs after treatment with low-dose aspirin alone, fish oil alone or a combination of these two therapies. Double-blinded randomised controlled clinical trial on 16 healthy client-owned dogs. Comprehensive haemostatic testing was performed at baseline and after 7 days of therapy with low-dose aspirin in all dogs. Following a 14-day washout, six dogs received fish oil, and nine dogs received combination therapy of aspirin plus fish oil; haemostatic testing was performed before and at 7 and 28 days after treatment initiation. Aspirin was associated with significantly decreased platelet function as measured by a collagen-epinephrine cartridge and inhibited arachidonic acid-induced whole-blood platelet aggregometry. Fish oil alone did not significantly affect any haemostatic tests. The combination of aspirin plus fish oil therapy caused a significantly greater inhibition of adenosine diphosphate and collagen-induced whole blood aggregometry compared to aspirin alone. Fish oil added to aspirin therapy appears to augment inhibition of some measures of platelet function in healthy dogs. © 2017 British Small Animal Veterinary Association.

Intralesional copper wire retention and pingyangmycin injection: an effective combinational therapy for complex venous malformation in soft tissue.

PubMed

Yuan, S-M; Hong, Z-J; Jiang, H-Q; Wang, J; Hu, X-B

2014-04-01

Complex venous malformations (VMs) may extensively involve the soft tissue. The treatment remains a challenge till now. Here we introduce a combinational therapy of copper wires and pingyangmycin (bleomycin A5,PYM). Copper wires were retained in VMs by repeated penetration with a straight needle. Subsequently, PYM solution was injected into the lesion. Eight to 10 days later, copper wires were removed. The dressing was changed every day until the puncture pores healed. Magnetic resonance imaging scanning was performed to observe the change of VMs. From January 2001 to December 2011, 56 patients were treated. During the follow-up period, most of the VMs shrunk obviously. The symptoms were relieved or disappeared. The complications included local pain, temporary paraesthesia and moderate fever, which disappeared quickly after the removal of copper wires. This combinational therapy is a safe and effective approach for the complex VMs in soft tissue.

Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

PubMed

Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

2017-07-01

Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials. Morin M, Carroll M-S, Bergeron S. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia. Sex Med Rev 2017;5:295-322. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Targeting EGFR with photodynamic therapy in combination with Erbitux enhances in vivo bladder tumor response

PubMed Central

Bhuvaneswari, Ramaswamy; Gan, Yik Yuen; Soo, Khee Chee; Olivo, Malini

2009-01-01

Background Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. Treatment induced hypoxia is one of the main side effects of PDT and efforts are underway to optimize PDT protocols for improved efficacy. The aim of this study was to investigate the anti-tumor effects of PDT plus Erbitux, an angiogenesis inhibitor that targets epidermal growth factor receptor (EGFR), on human bladder cancer model. Tumor-bearing nude mice were assigned to four groups that included control, PDT, Erbitux and PDT plus Erbitux and tumor volume was charted over 90-day period. Results Our results demonstrate that combination of Erbitux with PDT strongly inhibits tumor growth in the bladder tumor xenograft model when compared to the other groups. Downregulation of EGFR was detected using immunohistochemistry, immunofluorescence and western blotting. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In addition, we identified the dephosphorylation of ErbB4 at tyrosine 1284 site to play a major role in tumor inhibition. Also, at the RNA level downregulation of EGFR target genes cyclin D1 and c-myc was observed in tumors treated with PDT plus Erbitux. Conclusion The combination therapy of PDT and Erbitux effectively inhibits tumor growth and is a promising therapeutic approach in the treatment of bladder tumors. PMID:19878607

Art therapy, psychodrama, and verbal therapy. An integrative model of group therapy in the treatment of adolescents with anorexia nervosa and bulimia nervosa.

PubMed

Diamond-Raab, Lisa; Orrell-Valente, Joan K

2002-04-01

Anorexia nervosa and bulimia nervosa typically afflict individuals in adolescence. Given the intractability of these diseases in combination with the natural recalcitrance of adolescence, treatment with this population presents a daunting challenge. Traditional group therapy that focuses on verbal therapy is often not effective with this population, particularly in the acute stages of the diseases. A group therapy approach that integrates art therapy, psychodrama, and verbal therapy offers an innovative alternative to traditional group therapy.

Cost-Effectiveness of Simvastatin Plus Ezetimibe for Cardiovascular Prevention in Patients With a History of Acute Coronary Syndrome: Analysis of Results of the IMPROVE-IT Trial.

PubMed

Almalki, Ziyad S; Guo, Jeff Jianfei; Alahmari, Abdullah; Alotaibi, Nawaf; Thaibah, Hilal

2018-06-01

Simvastatin plus ezetimibe reduced the risk of cardiovascular events in the IMProved Reduction of Outcomes: Vytorin Efficacy International (IMPROVE-IT) study. The aim of this study is to investigate the cost-effectiveness of adding ezetimibe to simvastatin treatment for patients with ACS based on the recently completed IMPROVE-IT trial. We constructed a Markov state-transition model to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness (ICER) associated with co-therapy compared with simvastatin alone from a health care perspective. We ran separate base-case analyses assuming a trial-length and longer term follow-up. One-way sensitivity analyses were used to explore uncertainty in model parameters. In the trial-length model, the ICERs compared with simvastatin alone were $114,400 per QALY for the combination therapy. In 5- and 10-year time horizons, the ICERs remained above the cost-effectiveness threshold of $50,000 per QALY. In the lifetime horizon model, The ICER was $45,046 per QALY for combination treatment compared with simvastatin alone. The combination therapy is cost-effective at an 80% decrease in the current branded simvastatin and ezetimibe cost. Probabilistic sensitivity analysis suggested simvastatin and ezetimibe co-therapy would be a cost-effective alternative to simvastatin monotherapy 60.7% of the time. In our trial-length, 5-year, and 10-year models, the co-therapy was not a cost-effective alternative; however, as follow-up was extended to lifetime, the co-therapy became a cost-effective treatment compared with the simvastatin monotherapy in patients with histories of ACS. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Effect of Exercise on Motor and Nonmotor Symptoms of Parkinson's Disease

PubMed Central

Dashtipour, Khashayar; Johnson, Eric; Kani, Camellia; Kani, Kayvan; Hadi, Ehsan; Ghamsary, Mark; Pezeshkian, Shant; Chen, Jack J.

2015-01-01

Background. Novel rehabilitation strategies have demonstrated potential benefits for motor and non-motor symptoms of Parkinson's disease (PD). Objective. To compare the effects of Lee Silverman Voice Therapy BIG (LSVT BIG therapy) versus a general exercise program (combined treadmill plus seated trunk and limb exercises) on motor and non-motor symptoms of PD. Methods. Eleven patients with early-mid stage PD participated in the prospective, double-blinded, randomized clinical trial. Both groups received 16 one-hour supervised training sessions over 4 weeks. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) and Modified Fatigue Impact Scale (MFIS). Five patients performed general exercise and six patients performed LSVT BIG therapy. Post-intervention evaluations were conducted at weeks 4, 12 and 24. Results. The combined cohort made improvements at all follow-up evaluations with statistical significance for UPDRS total and motor, BDI, and MFIS (P < 0.05). Conclusion. This study demonstrated positive effects of general exercise and LSVT BIG therapy on motor and non-motor symptoms of patients with PD. Our results suggest that general exercise may be as effective as LSVT BIG therapy on symptoms of PD for patients not able to readily access outpatient LSVT BIG therapy. PMID:25722915

The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells

PubMed Central

Alayev, Anya; Berger, Sara Malka; Kramer, Melissa Y.; Schwartz, Naomi S.; Holz, Marina K.

2015-01-01

Hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) is a frequent event in breast cancer and current efforts are aimed at targeting the mTORC1 signaling pathway in combination with other targeted therapies. However, patients often develop drug resistance in part due to activation of the oncogenic Akt signaling and upregulation of autophagy, which protects cancer cells from apoptosis. In the present study we investigated the effects of combination therapy of rapamycin (an allosteric mTORC1 inhibitor) together with resveratrol (a phytoestrogen that inhibits autophagy). Our results show that combination of these drugs maintains inhibition of mTORC1 signaling, while preventing upregulation of Akt activation and autophagy, causing apoptosis. Additionally, this combination was effective in estrogen receptor positive and negative breast cancer cells, underscoring its versatility. PMID:25336146

Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

PubMed

Lima, Glaura C; Silva, Emilia V; Magalhães, Pérola de O; Naves, Janeth S

Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance. To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis. A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment. The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

PDC-SGB: Prediction of effective drug combinations using a stochastic gradient boosting algorithm.

PubMed

Xu, Qian; Xiong, Yi; Dai, Hao; Kumari, Kotni Meena; Xu, Qin; Ou, Hong-Yu; Wei, Dong-Qing

2017-03-21

Combinatorial therapy is a promising strategy for combating complex diseases by improving the efficacy and reducing the side effects. To facilitate the identification of drug combinations in pharmacology, we proposed a new computational model, termed PDC-SGB, to predict effective drug combinations by integrating biological, chemical and pharmacological information based on a stochastic gradient boosting algorithm. To begin with, a set of 352 golden positive samples were collected from the public drug combination database. Then, a set of 732 dimensional feature vector involving biological, chemical and pharmaceutical information was constructed for each drug combination to describe its properties. To avoid overfitting, the maximum relevance & minimum redundancy (mRMR) method was performed to extract useful ones by removing redundant subsets. Based on the selected features, the three different type of classification algorithms were employed to build the drug combination prediction models. Our results demonstrated that the model based on the stochastic gradient boosting algorithm yield out the best performance. Furthermore, it is indicated that the feature patterns of therapy had powerful ability to discriminate effective drug combinations from non-effective ones. By analyzing various features, it is shown that the enriched features occurred frequently in golden positive samples can help predict novel drug combinations. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2009-03-01

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

[11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy.

PubMed

Schwarzenböck, Sarah M; Knieling, Anna; Souvatzoglou, Michael; Kurth, Jens; Steiger, Katja; Eiber, Matthias; Esposito, Irene; Retz, Margitta; Kübler, Hubert; Gschwend, Jürgen E; Schwaiger, Markus; Krause, Bernd J; Thalgott, Mark

2016-09-27

Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma.

PubMed

Cabello, I; Servitje, O; Corbella, X; Bardés, I; Pintó, X

2017-04-01

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia. To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene. From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA. Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination. Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia. © 2017 British Association of Dermatologists.

Oxygen-driving and atomized mucosolvan inhalation combined with holistic nursing in the treatment of children severe bronchial pneumonia.

PubMed

Yang, Fang

2015-07-01

This paper aimed to discuss the method, effect and safety of oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing in the treatment of children severe bronchial pneumonia. Totally 90 children with severe bronchial pneumonia who were treated in our hospital from March 2013 to November 2013 were selected as the research objects. Based on randomized controlled principle, those children were divided into control group, test group I and test group II according to the time to enter the hospital, 30 in each group. Patients in control group was given conventional therapy; test group I was given holistic nursing combined with conventional therapy; test group II was given oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing on the basis of conventional therapy. After test, the difference of main symptoms in control group, test group I and II was of no statistical significance (P>0.05). Test group II was found with the best curative effect, secondary was test group I and control group was the last. It can be concluded that, oxygen-driving and atomized Mucosolvan inhalation combined with holistic nursing has certain effect in the treatment of children severe bronchial pneumonia and is better than holistic nursing only.

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

PubMed

Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

2017-07-01

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

[Diagnostic and therapy of tension-type headache].

PubMed

Straube, A

2014-08-01

Episodic headache of the tension type is the most prevalent primary headache with a lifetime prevalence of about 78 %. Clinical characteristics are a dull, moderate, holocephalic headache without accompanying autonomic or vegetative symptoms. The episodic tension-type headache often lasts only 30 min up to a maximum of a few days. In contrast to this clinically often undemanding headache, chronic tension-type headache can cause considerable disability in patients. The 1-year prevalence is 1-3 % of the population. All therapy strategies combine nonpharmaceutical therapy such as education of the patient, regular aerobic exercise, and psychological treatment (e.g., Jacobson's progressive muscle relaxation etc.) with pharmaceutical treatment such as tricyclic antidepressants or combined serotonergic and noradrenergic antidepressants. Combination therapy has been proven to be more effective than singular strategies; however, the chronic tension-type headache still poses a therapeutic problem.

An Updated Review of the Efficacy of Cupping Therapy

PubMed Central

Cao, Huijuan; Li, Xun; Liu, Jianping

2012-01-01

Background Since 1950, traditional Chinese medicine (TCM) cupping therapy has been applied as a formal modality in hospitals throughout China and elsewhere in the world. Based on a previous systematic literature review of clinical studies on cupping therapy, this study presents a thorough review of randomized controlled trials (RCTs) to evaluate the therapeutic effect of cupping therapy. Method Six databases were searched for articles published through 2010. RCTs on cupping therapy for various diseases were included. Studies on cupping therapy combined with other TCM treatments versus non-TCM therapies were excluded. Results 135 RCTs published from 1992 through 2010 were identified. The studies were generally of low methodological quality. Diseases for which cupping therapy was commonly applied were herpes zoster, facial paralysis (Bell palsy), cough and dyspnea, acne, lumbar disc herniation, and cervical spondylosis. Wet cupping was used in most trials, followed by retained cupping, moving cupping, and flash cupping. Meta-analysis showed cupping therapy combined with other TCM treatments was significantly superior to other treatments alone in increasing the number of cured patients with herpes zoster, facial paralysis, acne, and cervical spondylosis. No serious adverse effects were reported in the trials. Conclusions Numerous RCTs on cupping therapy have been conducted and published during the past decades. This review showed that cupping has potential effect in the treatment of herpes zoster and other specific conditions. However, further rigorously designed trials on its use for other conditions are warranted. PMID:22389674

Systematic review with meta-analysis: infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis.

PubMed

Christophorou, D; Funakoshi, N; Duny, Y; Valats, J-C; Bismuth, M; Pineton De Chambrun, G; Daures, J-P; Blanc, P

2015-04-01

The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC). To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use. We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4-6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed. Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4-6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34-0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47-0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17-2.06], P = 0.41 (P-heterogeneity = 0.01). Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4-6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use. © 2015 John Wiley & Sons Ltd.

[Tadalafil combined with behavior therapy for semen collection from infertile males in whom masturbation fails].

PubMed

Tang, Wen-Hao; Jiang, Hui; Ma, Lu-Lin; Hong, Kai; Zhao, Lian-Ming; Liu, De-Feng; Mao, Jia-Ming; Yang, Yi; Zhang, Ju; Gao, Ling; Qiao, Jie

2013-05-01

To study the effect of Tadalafil combined with behavior therapy in helping obtain semen from infertile men in whom masturbation has failed. Sixty male infertile patients from whom masturbation had failed to obtain semen were equally assigned to receive Tadalafil combined with behavior therapy (combination group) or Tadalafil only (control group). All the patients took Tadalafil 20 mg orally the night before the day of semen collection by masturbation. Before this procedure, the patients of the combination group practiced masturbation 16 - 24 times at home. The average ages of the patients were (37.0 +/- 5.1) yr and (37.5 +/- 5.2) yr and their IIEF-5 scores were 16.50 +/- 1.25 and 16.90 +/- 1.09 in the combination and the control group, respectively, neither with statistically significant difference between the two groups. Semen was successfully obtained from 9 patients (30.0%) of the combination group and 1 patient (3.33%) of the control group, with statistically significant difference between the two groups (chi2 = 7.680, P < 0.01). By training the patients and establishing a conditioned response to masturbation, Tadalafil combined with behavior therapy can significantly increase the success rate of semen collection from the male infertile patients in whom masturbation fails.

Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

PubMed

Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

2017-08-28

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vitro Assessment of Combined Polymyxin B and Minocycline Therapy against Klebsiella pneumoniae Carbapenemase (KPC)-Producing K. pneumoniae.

PubMed

Huang, Dennis; Yu, Brenda; Diep, John K; Sharma, Rajnikant; Dudley, Michael; Monteiro, Jussimara; Kaye, Keith S; Pogue, Jason M; Abboud, Cely Saad; Rao, Gauri G

2017-07-01

The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based combination treatments have been reported for infections caused by carbapenemase-producing bacteria. The objective of this study was to evaluate the in vitro activity of polymyxin B and minocycline combination therapy against six KPC-2-producing K. pneumoniae isolates (minocycline MIC range, 2 to 32 mg/liter). Polymyxin B monotherapy (0.5, 1, 2, 4, and 16 mg/liter) resulted in a rapid reduction of up to 6 log in bactericidal activity followed by regrowth by 24 h. Minocycline monotherapy (1, 2, 4, 8, and 16 mg/liter) showed no reduction of activity of >1.34 log against all isolates, although concentrations of 8 and 16 mg/liter prolonged the time to regrowth. When the therapies were used in combination, rapid bactericidal activity was followed by slower regrowth, with synergy (60 of 120 combinations at 24 h, 19 of 120 combinations at 48 h) and additivity (43 of 120 combinations at 24 h, 44 of 120 combinations at 48 h) against all isolates. The extent of killing was greatest against the more susceptible polymyxin B isolates (MICs of ≤0.5 mg/liter) regardless of the minocycline MIC. The pharmacodynamic activity of combined polymyxin B-minocycline therapy against KPC-producing K. pneumoniae is dependent on polymyxin B susceptibility. Further in vitro and animal studies must be performed to fully evaluate the efficacy of this drug combination. Copyright © 2017 American Society for Microbiology.

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

PubMed

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

2018-04-01

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

[Recent Advances in Immunotherapy for Non-Small Cell Lung Cancer].

PubMed

Muto, Satoshi; Suzuki, Hiroyuki

2018-02-01

Cancer immunotherapy for non-small cell lung cancer began around 1970 with nonspecific immunomodulators and cytokine therapies. This has since developed into cell therapy including lymphokine-activated killer cells(LAK)and tumor infiltrating lymphocytes(TIL), as well as cancer vaccine therapy. However, no clear indication of effectiveness has been reported. Despite the high expectation over the effectiveness of cancer vaccine therapy, the treatment strategy was deemed unsuccessful, and focus turned to the study of immune escape mechanism, which is now regarded as standard treatment for non-small cell lung cancer. With the advent of immune checkpoint inhibitors, cancer immunotherapy has finally become a standard treatment for non-small cell lung cancer. There are still several obstacles to overcome including the identification of a predictive biomarker for improved efficacy, as well as the establishment of multidrug or multimodality combination therapy. PD-L1 expression is currently used as a predictive biomarker for anti-PD-1 therapy, but does not meet the expectations of the aimed results. Although tumor mutation burden is considered another promising biomarker, there remain clinical problems, for example the need of next generation sequencer. It was reported that combination therapy of immune checkpoint inhibitor after chemoradiation therapy was also effective. However, it remains unclear of what is required to further improve the clinical effects. In this article, we will review the history of cancer immunotherapy for non-small cell lung cancer and discuss the future prospects.

Peptide micelle-mediated delivery of tissue-specific suicide gene and combined therapy with avastin in a glioblastoma model.

PubMed

Oh, Binna; Han, Jaesik; Choi, Eunji; Tan, Xiaonan; Lee, Minhyung

2015-04-01

Bevacizumab (Avastin) is an angiogenesis inhibitor used as a treatment for various cancers. In this study, the combination therapy of Avastin and glioblastoma-specific thymidine kinase gene [pEpo-NI2-SV-herpes simplex virus thymidine kinase(HSVtk)] was evaluated in a glioblastoma animal model. The R7L10 peptide was used as a gene carrier of pEpo-NI2-SV-HSVtk. Gel retardation assays confirmed that R7L10 formed stable complexes with pEpo-NI2-SV-HSVtk. R7L10 protected DNA from nuclease digestion. R7L10 had lower transfection efficiency than polyethylenimine (PEI; 25 kDa). However, the in vitro and in vivo toxicity assays showed that R7L10 had lower cytotoxicity than PEI, suggesting that R7L10 is safer than PEI. For the combination therapy, Avastin was injected intravenously and the pEpo-NI2-SV-HSVtk/R7L10 complexes were injected intratumorally in the glioblastoma animal model. Tumor growth was most effectively inhibited by the combination therapy of Avastin and the gene. The immunostaining results confirmed that the HSVtk genes were expressed in the groups with the pEpo-NI2-SV-HSVtk/R7L10 complex. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed a higher level of apoptotic cells in the combination group than the pEpo-NI2-SV-HSVtk/R7L10 complex or Avastin group. In conclusion, the combination of Avastin and the glioblastoma-specific HSVtk gene has a higher antitumor effect than single therapy of Avastin or HSVtk after intratumoral administration in glioblastoma animal model. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young β-thalassemia intermedia patients.

PubMed

Elalfy, Mohsen S; Adly, Amira A M; Ismail, Eman A; Elhenawy, Yasmine I; Elghamry, Islam R

2013-12-01

To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in β-thalassemia intermedia (TI) patients compared with single HU therapy. An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study. Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups. HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study.

PubMed

Ibrahim, Iman; Zeitouni, Anthony; da Silva, Sabrina Daniela

2018-06-22

Sudden sensorineural hearing loss (SSNHL) is an otological emergency of unknown etiology. Recent reports showed that antioxidant drugs can benefit patients with SSNHL. This study attempted to evaluate the effect of adding antioxidant vitamins as an adjuvant therapy alongside with corticosteroids. To evaluate the effects of the 3 major antioxidant vitamins (A, C, and E) as an adjuvant therapy, administered with corticosteroids, for the treatment of SSNHL in adult patients (≥18 years). MEDLINE, EMBASE, PubMed, Web of Science and Cochrane electronic databases from January 1, 1995, through September 25, 2017. Published studies of adult patients who received antioxidant vitamins (A, C, E, or any combination of these vitamins) as an adjuvant therapy in addition to the regular treatment (corticosteroids) for SSNHL. Quality assessment was performed using the Cochrane Collaboration Tool for Assessing Risk of Bias. Each study had a control group (conventional treatment + placebo) and a trial group (antioxidant vitamin(s) + conventional treatment). From 446 manuscripts identified in the literature, 3 studies were included in the review with 279 patients. The most common vitamins used to treat SSNHL were the 3 major antioxidant vitamins A, C, and E, combined sometimes with other antioxidants such as selenium. The success of the treatment is increased in patients who received antioxidant vitamins in combination with conventional therapy. © 2018 S. Karger AG, Basel.

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

NASA Astrophysics Data System (ADS)

Zhu, Dao-Ming; Xie, Wei; Xiao, Yu-Sha; Suo, Meng; Zan, Ming-Hui; Liao, Qing-Quan; Hu, Xue-Jia; Chen, Li-Ben; Chen, Bei; Wu, Wen-Tao; Ji, Li-Wei; Huang, Hui-Ming; Guo, Shi-Shang; Zhao, Xing-Zhong; Liu, Quan-Yan; Liu, Wei

2018-02-01

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease.

PubMed

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days' treatment. after 30 days' treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function.

The evaluation of clinical therapy effects of oral western medicine combined with magnetic pulse acupoint stimulation in treating elderly patients with coronary heart disease

PubMed Central

Fu, Xin; Guo, Li; Jiang, Zheng-Ming; Xu, Ai-Guo

2015-01-01

Objective: Treat the patients suffered from coronary heart disease with oral western medicine, combining with magnetic pulse acupoint stimulation, and observe the therapeutic effects of such combination therapy method. Methods: 56 old people with coronary heart disease are randomly divided into a treatment group and a control group. Both groups of patients are treated by the routine drugs, in addition, the patients of the treatment group are treated by magnetic pulse therapy additionally. Compare clinical symptoms, blood lipid and blood rheological indexes of the patients in the two groups when they are selected and after 30 days’ treatment. Results: after 30 days’ treatment, it is found that clinical symptoms, blood lipid and blood rheological indexes of the patients in the treatment group are significantly improved compared with those when they are selected and those of the control group (P<0.05). Conclusion: patients with coronary heart disease, treated by pulsed magnetic therapy and the conventional drug intervention, had relieved synptom, improve blood lipid and heart blood supply function. PMID:26309664

Treatment of dyslipidemia in HIV-infected patients.

PubMed

Sekhar, Rajagopal V; Balasubramanyam, Ashok

2010-08-01

Patients infected with HIV are at high risk for dyslipidemia, insulin resistance and cardiovascular disease. Therapies to reverse these risks are complex, sometimes controversial, and not uniformly effective. Pathophysiology of the lipid abnormalities in HIV is discussed, including the causes of alterations in triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and insulin resistance. We discuss the therapy of dyslipidemia in HIV using a combination of available clinical evidence and expert opinion based on extensive clinical experience, with discussions of lifestyle intervention and diet, conventional pharmacotherapy with lipid-lowering medications including statins, fibrates, niacin and thiazolidinediones for dyslipidemia, and newer therapeutic approaches including omega fatty acids, acipimox, growth hormone and leptin. A detailed understanding of the pathophysiology and rational or evidence-based approach to therapy of lipid abnormalities in patients infected with HIV. Treatment of dyslipidemia in patients with HIV is challenging and complicated by the risk of drug interactions. Appropriate therapy requires a sound understanding of pathophysiology and the principles of pharmacological and nonpharmacological therapeutic interventions. An evidence-based approach that combines lifestyle changes and drugs that are both safe and effective, singly and in combination, is described.

Effectiveness of hydroplasty and therapeutic exercise for treatment of frozen shoulder.

PubMed

Callinan, Nancy; McPherson, Scott; Cleaveland, Susan; Voss, Debra Gardiner; Rainville, Darcel; Tokar, Nancy

2003-01-01

The purpose of this retrospective review was to evaluate the effectiveness of a hydraulic distention technique (hydroplasty) combined with a therapy program for treatment of idiopathic frozen shoulder. Over a two-year period, 60 patients with idiopathic frozen shoulder were identified as having undergone the hydroplasty procedure and therapy protocol at the authors' hand center. Distention of the glenohumeral joint was achieved by an injection of a 10-mL combination of bupivacaine (Marcaine), lidocaine (Xylocaine), and corticosteroid followed by injection of 30 mL of chilled sterile normal saline. Therapy was initiated immediately after the surgeon had completed the hydroplasty. The mean active range of motion improvement was as follows: flexion 28 degrees, abduction 42 degrees, internal rotation 22 degrees, and external rotation 26 degrees. There was no significant difference in outcomes between diabetics and nondiabetics or subjects with symptoms less than six months' duration compared with subjects with symptom duration greater than six months. At discharge, only two (3%) of the subjects reported persistent pain during sleep. The hydroplasty procedure combined with a therapy program is a successful treatment for idiopathic frozen shoulder.

Pain therapy with oxycodone/naloxone prolonged-release combination: case report

PubMed Central

Droń, Aleksandra

2013-01-01

Pain afflicts patients suffering from many chronic diseases and is present in 80% of cases of patients with advanced cancer who suffer from persistent pain. The aim of the pain treatment is to achieve the maximum analgesic effect while minimizing side effects. The main analgesic agent – morphine is unfortunately a therapy associated with gastrointestinal side effects. It appears that the combination of oxycodone and naloxone available as Targin® (Mundipharma) is an alternative. The paper presents a case of a 45-year-old patient who was treated effectively with oxycodone/naloxone prolonged-release tablets. This treatment has proven to be effective in providing pain and constipation control. PMID:24592131

Does combined therapy of curcumin and epigallocatechin gallate have a synergistic neuroprotective effect against spinal cord injury?

PubMed

Ruzicka, Jiri; Urdzikova, Lucia Machova; Svobodova, Barbora; Amin, Anubhav G; Karova, Kristyna; Dubisova, Jana; Zaviskova, Kristyna; Kubinova, Sarka; Schmidt, Meic; Jhanwar-Uniyal, Meena; Jendelova, Pavla

2018-01-01

Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests (the Basso, Beattie, and Bresnahan (BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods (Luxol Blue-cresyl violet staining) and immunohistochemistry (anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels (interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes (Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.

Combination of photodynamic therapy and immunotherapy - evolving role in dermatology

NASA Astrophysics Data System (ADS)

Wang, Xiu-Li; Wang, Hong-Wei; Huang, Zheng

2008-02-01

Photodynamic therapy (PDT) is a promising treatment modality. It offers alternative options in the treatment of cancer and vascular diseases. In cancer treatment, PDT has been used primarily for localized superficial or endoluminal malignant and premalignant conditions. More recently, its application has also been expanded to solid tumors. However, its antitumor efficacy remains debatable and its acceptance still variable. Pre-clinical studies demonstrate that, in addition to the primary local cytotoxicity, PDT might induce secondary host immune responses, which may further enhance PDT's therapeutic effects on primary tumor as well as metastasis. Therefore, PDT-induced local and systemic antitumor immune response might play an important role in successful control of malignant diseases. Furthermore, PDT's antitumor efficacy might also be enhanced through an effective immunoadjuvant or immunomodulator. Our recent clinical data also indicate that improved clinical outcomes can be obtained by a combination of PDT and immunomodulation therapy for the treatment of pre-malignant skin diseases. For instance, the combination of topical ALA-PDT and Imiquimod is effective for the treatment of genital bowenoid papulosis. This presentation will also report our preliminary data in developing combination approaches of PDT and immunotherapy for actinic keratosis (AK), basal cell carcinomas (BCCs) and Bowen's disease.

Retrospective chart review of children with type 2 diabetes mellitus evaluating the efficacy of metformin vs. insulin vs. combination insulin/metformin.

PubMed

Meyer, Stacy L; Hoffman, Robert P

2011-10-01

Type 2 diabetes mellitus is a growing problem in pediatrics and there is no consensus on the best treatment. We conducted this chart review on newly diagnosed pediatric patients with type 2 diabetes mellitus to compare the effect of treatment regimen on body mass index (BMI) and hemoglobin A1c over a 6-month period. We conducted a retrospective chart review on patients with type 2 DM who presented to Nationwide Children's Hospital. Data were collected on therapy type, BMI, and hemoglobin A1c over a 6-month follow-up. Therapy type was divided into metformin, insulin, or combination insulin and metformin. 1,997 charts were reviewed for inclusion based on ICD-9 codes consistent with a diagnosis of diabetes, abnormal oral glucose tolerance test, or insulin resistance. Of the 47 charts eligible for the review, 26 subjects were treated with metformin 1000-1500 mg daily, 14 patients were treated with insulin therapy, and 7 patients were treated with a combination of insulin and metformin therapy. At baseline, the only significant difference among groups was A1c (P = 0.012). In regression analysis with baseline A1c as a covariate, the only predictor of change in A1c over time was the A1c at onset (P < 0.001). Therapy type was not predictive of change (P = 0.905). Regression analysis showed a greater BMI at onset predicted a greater decrease in BMI (P = 0.006), but therapy type did not predict a change (P = 0.517). Metformin may be as effective as insulin or combination therapy for treatment of diabetes from onset to 6-month follow-up.

Targeting glycolysis by 3-bromopyruvate improves tamoxifen cytotoxicity of breast cancer cell lines.

PubMed

Attia, Yasmin M; El-Abhar, Hanan S; Al Marzabani, Mahmoud M; Shouman, Samia A

2015-11-03

Tamoxifen is the standard endocrine therapy for ER+ breast cancer; however, many women still relapse after long-term therapy. 3-Bromopyruvate, a glycolytic inhibitor, has shown high selective anti-tumor activity in vitro, and in vivo. The aim of this study was to evaluate the possible augmentation of the effect of tamoxifen via reprograming cancer cell metabolism using 3-bromopyruvate. An in vitro screening of antitumor activity as well as the apoptotic, anti-metastatic, and anti-angiogenic potentials of the combination therapy were carried out using different techniques on breast cancer cell lines MCF7and T47D. In addition the antitumor effect of the combined therapy was done on mice bearing tumor. Our results showed modulation in apoptosis, angiogenesis and metastatic potential by either drug alone; however, their combination has surpassed that of the individual one. Combination regimen enhanced activated caspases-3, 7 and 9, as well as oxidative stress, signified by increased malondialdehyde and decreased glutathione level. Additionally, the angiogenesis and metastasis markers, including hypoxia inducing factor-1α, vascular endothelia growth factor, and metaloproteinases-2 and 9 were decreased after using the combination regimen. These results were further confirmed by the in vivo study, which depicted a decrease in the tumor volume and angiogenesis and an increase in oxidative stress as well. 3-bromopyruvate could be a valuable compound when added with tamoxifen in breast cancer treatment.

Oncolytic vaccinia virus combined with radiotherapy induces apoptotic cell death in sarcoma cells by down-regulating the inhibitors of apoptosis

PubMed Central

Wilkinson, Michelle J.; Smith, Henry G.; McEntee, Gráinne; Kyula-Currie, Joan; Mansfield, David C.; Khan, Aadil A.; Roulstone, Victoria

2016-01-01

Advanced extremity melanoma and sarcoma present a significant therapeutic challenge, requiring multimodality therapy to treat or even palliate disease. These aggressive tumours are relatively chemo-resistant, therefore new treatment approaches are urgently required. We have previously reported on the efficacy of oncolytic virotherapy (OV) delivered by isolated limb perfusion. In this report, we have improved therapeutic outcomes by combining OV with radiotherapy. In vitro, the combination of oncolytic vaccinia virus (GLV-1h68) and radiotherapy demonstrated synergistic cytotoxicity. This effect was not due to increased viral replication, but mediated through induction of intrinsic apoptosis. GLV-1h68 therapy downregulated the anti-apoptotic BCL-2 proteins (MCL-1 and BCL-XL) and the downstream inhibitors of apoptosis, resulting in cleavage of effector caspases 3 and 7. In an in vivo ILP model, the combination of OV and radiotherapy significantly delayed tumour growth and prolonged survival compared to single agent therapy. These data suggest that the virally-mediated down-regulation of anti-apoptotic proteins may increase the sensitivity of tumour cells to the cytotoxic effects of ionizing radiation. Oncolytic virotherapy represents an exciting candidate for clinical development when delivered by ILP. Its ability to overcome anti-apoptotic signals within tumour cells points the way to further development in combination with conventional anti-cancer therapies. PMID:27783991

Effectiveness and clinical predictors of response to combined ECT and antipsychotic therapy in patients with treatment-resistant schizophrenia and dominant negative symptoms.

PubMed

Pawełczyk, Tomasz; Kołodziej-Kowalska, Emilia; Pawełczyk, Agnieszka; Rabe-Jabłońska, Jolanta

2014-12-15

The effectiveness and predictors of response to electroconvulsive therapy (ECT) combined with antipsychotics (AP) in treatment-resistant schizophrenia patients with the dominance of negative symptoms (TRS-NS) have not been studied systematically so far. 29 patients aged 21-55 years diagnosed with TRS-NS underwent ECT combined with antipsychotics (ECT+AP). Prior to the ECT, the symptom profile and severity were evaluated using Positive and Negative Syndrome Scale (PANSS). Demographic and medical data was collected; ECT parameters and pharmacotherapy results were evaluated. After the combined ECT+AP therapy a significant decrease in symptom severity was found. A response to treatment was achieved by 60% of patients. The greatest reductions were obtained in general and positive PANSS subscale (median change: 11 and 7 pts.) and the smallest, but still significant, ones in negative symptoms subscale (median: 3.5 pts.). Patients who responded to ECT+AP demonstrated a significantly shorter duration of the current episode in comparison with patients who did not experience at least a 25% reduction in symptom severity (median: 4 vs. 8 months). A combination of ECT and antipsychotic therapy can provide a useful treatment option for patients with TRS-NS. The only significant predictor of response to treatment was a shorter duration of the current episode. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Synergistic effect of the combination of triethylene-glycol modified Fe3O4 nanoparticles and ultrasound wave on MCF-7 cells

NASA Astrophysics Data System (ADS)

Ebrahimi Fard, Ali; Zarepour, Atefeh; Zarrabi, Ali; Shanei, Ahmad; Salehi, Hossein

2015-11-01

Cancer is a group of disease characterized by uncontrolled growth and spread of abnormal cells in the body. The clinical treatments for cancer include surgery, chemotherapy and radiotherapy. Currently, employing new approaches for treatment has attracted more attentions. One of these approaches is sonodynamic therapy, which is an analogous approach based on the synergistic effect of ultrasound and a chemical component referred to as sonosensitizer. Recent years applications of nanotechnology have witnessed a tremendous expansion of research in medicine especially in treatment of cancers. The combination of sonodynamic therapy and nanotechnology can introduce a new way for cancer therapy. In this study, we used therapeutic ultrasonic waves with intensity of 1 MHz and different concentrations of Fe3O4 nanoparticles, as sonosensitizer, to investigate their combination effect on MCF-7 cell line. Briefly, we divided cells into four different groups; control, cells which got in touch with nanoparticles, cells that with exposure to ultrasound waves and cells which were influenced with combination of nanoparticles and ultrasonic waves. Finally, cell viability assay was used for detection of cytotoxicity effects. Experimental results revealed a significant decrease in viability of cells, which were affected by the combined action of ultrasound field and Fe3O4 nanoparticles, compared to the separate exposure of Fe3O4 nanoparticles or ultrasonic field. The synergic effect of ultrasound waves and Fe ions might be due to the production of toxic free radicals.

[Effect of different therapy options on bronchial contraction in rats with modeled obstructive pulmonary disease].

PubMed

Kuzubova, N A; Fedin, A N; Lebedeva, E S; Platonova, I S

2014-09-01

In the model of chronic obstructive pulmonary disease, produced in rats by 60-day exposure to nitrogen dioxide, the effect of different options of combination therapy (corticosteroids, anticholinergics, adrenergic agonists) on the functional state of the bronchi was studied. The contractile activity of strips of the bronchi caused by nerve or smooth muscle stimulation was evaluated. Corticosteroid monotherapy resulted in deterioration of the functional state of the bronchial wall neuromuscular apparatus due to corticosteroid resistance, evolving under the influence of long-term exposure to nitrogen dioxide. Application of M-anticholinergic tiotropium had a beneficial effect on the functional state of the bronchi smooth muscles, leading to the full restoration of the bronchial wall contractile activity and removal the morphological manifestations of inflammatory lung tissue remodeling. Most effective in terms of impact on the functional state of the bronchial wall neuromuscular apparatus was corticosteroid therapy combined with M-cholinolytik or beta2-adrenoagonist.

Effects of Long-Term Combination LT4 and LT3 Therapy for Improving Hypothyroidism and Overall Quality of Life.

PubMed

Tariq, Anam; Wert, Yijin; Cheriyath, Pramil; Joshi, Renu

2018-06-01

Hypothyroidism results in decreased mood and neurocognition, weight gain, fatigue, and many other undesirable symptoms. The American Association of Clinical Endocrinologists, the American Thyroid Association (ATA), and The Endocrine Society recommend levothyroxine (LT4) monotherapy as the treatment for hypothyroidism; however, after years of monotherapy, some patients continue to experience impaired quality of life. Combination LT4 and synthetic liothyronine (LT3) therapy or the use of desiccated thyroid extract (DTE), has not been suggested for this indication based on short-duration studies with no significant benefits. Our first observational study examined the role of combination therapy for 6 years in improving quality of life in a subset of a hypothyroid population without adverse effects and cardiac mortality. An observational retrospective study examining patients prescribed thyroid replacements with serum triiodothyronine (FT3), LT4 with LT3 (synthetic therapy) or DTE (natural therapy), compared with LT4 alone in the United States from 2010 to 2016. Thyroid-stimulating hormone (TSH), serum thyroxine (FT4), and FT3 levels were documented for each patient in addition to any admissions of myxedema coma, thyrotoxicosis, or cardiovascular complications, such as arrhythmias, atrial fibrillation, and mortality. At the conclusion of the study, a cross-sectional interview assessed quality of life for each combination therapy through the Medical Outcomes Study Short Form-20 questionnaire. Compared with patients taking only LT4, 89.47% using synthetic therapy had therapeutic TSH ( P < 0.05). Similarly, 96.49% using natural therapy had therapeutic TSH ( P < 0.05). Less than 5% of patients had supratherapeutic FT3. None of the patients who had abnormally low TSH or elevated FT3 or FT4 levels had hospitalizations for arrhythmias or thyrotoxicosis. On the Medical Outcomes Study Short Form-20 questionnaire, >92% answered feeling "excellent, very good, or good" when questioned about their health while undergoing thyroid replacement compared with levothyroxine alone. This is the only retrospective study reported to use long-term (mean 27 months) thyroid replacements with combination therapy and to compare between the two forms of therapy: synthetic and natural. For patients undergoing either therapy, we did not identify additional risks of atrial fibrillation, cardiovascular disease, or mortality in patients of all ages with hypothyroidism.

Psychological treatments for epilepsy.

PubMed

Ramaratnam, S; Baker, G A; Goldstein, L

2001-01-01

Psychological interventions such as relaxation therapy, cognitive behaviour therapy, EEG bio-feedback and educational interventions have been used alone or in combination in the treatment of epilepsy, to reduce the seizure frequency and improve the quality of life. To assess whether the treatment of epilepsy with psychological methods is effective in reducing seizure frequency and/or leads to a better quality of life. We searched the Cochrane Epilepsy Group trial register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE using OVID (1966 - May 2001) and cross references from identified publications. Randomized or quasi-randomized studies assessing one or more types of psychological or behaviour modification techniques for patients with epilepsy. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included reduction in seizure frequency, and quality of life. We found three small trials (50 patients) of relaxation therapy. They were of poor methodological quality and a meta-analysis was therefore not undertaken. No study found a significant effect of relaxation therapy on seizure frequency. One trial found cognitive behavioural therapy to be effective in reducing depression, among people with epilepsy with a depressed affect, whilst another did not. One trial of group cognitive therapy found no significant effect on seizure frequency. Two trials of combined relaxation and behaviour therapy and one of EEG bio-feedback and two of educational interventions did not provide sufficient information to assess their effect on seizure frequency. Combined use of relaxation and behaviour modification was found beneficial for anxiety and adjustment in one study. In one study EEG bio-feedback was found to improve the cognitive and motor functions in subjects with greatest seizure reduction. Educational interventions were found to be beneficial in improving the knowledge and understanding of epilepsy, improving compliance to medication and improving social competencies. In view of methodological deficiencies and limited number of patients studied, we have found no reliable evidence to support the use of these treatments and further trials are needed.

Chelation of Thallium (III) in Rats Using Combined Deferasirox and Deferiprone Therapy.

PubMed

Salehi, Samie; Saljooghi, Amir Sh; Badiee, Somayeh; Moqadam, Mojtaba Mashmool

2017-10-01

Thallium and its compounds are a class of highly toxic chemicals that cause wide-ranging symptoms such as gastrointestinal disturbances; polyneuritis; encephalopathy; tachycardia; skin eruptions; hepatic, renal, cardiac, and neurological toxicities; and have mutagenic and genotoxic effects. The present research aimed to evaluate the efficacy of the chelating agents deferasirox (DFX) and deferiprone (L1) in reducing serum and tissue thallium levels after the administration of thallium (III), according to two different dosing regimens, to several groups of Wistar rats for 60 days. It was hypothesized that the two chelators might be more efficient as a combined therapy than as monotherapies in removing thallium (III) from the rats' organs. The chelators were administered orally as either single or combined therapies for a period of 14 days. Serum and tissue thallium (III) and iron concentrations were determined by flame atomic absorption spectroscopy. Serum and tissue thallium (III) levels were significantly reduced by combined therapy with DFX and L1. Additionally, iron concentrations returned to normal levels and symptoms of toxicity decreased.

Challenges, solutions, and recommendations for Alzheimer's disease combination therapy.

PubMed

Hendrix, James A; Bateman, Randall J; Brashear, H Robert; Duggan, Cynthia; Carrillo, Maria C; Bain, Lisa J; DeMattos, Ronald; Katz, Russell G; Ostrowitzki, Susanne; Siemers, Eric; Sperling, Reisa; Vitolo, Ottavio V

2016-05-01

Given the complex neuropathology Alzheimer's disease (AD), combination therapy may be necessary for effective treatment. However, scientific, pragmatic, regulatory, and business challenges need to be addressed before combination therapy for AD can become a reality. Leaders from academia and industry, along with a former member of the Food and Drug Administration and the Alzheimer's Association, have explored these challenges and here propose a strategy to facilitate proof-of-concept combination therapy trials in the near future. First, a more integrated understanding of the complex pathophysiology and progression of AD is needed to identify the appropriate pathways and the disease stage to target. Once drug candidates are identified, novel clinical trial designs and selection of appropriate outcome assessments will be needed to enable definition and evaluation of the appropriate dose and dosing regimen and determination of efficacy. Success in addressing this urgent problem will only be achieved through collaboration among multiple stakeholders. Copyright © 2016 Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

[Potentiation of anti-ischemic and anti-anginal action of nitrates by hydrogen sulfide balneotherapy in patients with angina of effort].

PubMed

Zunnunov, Z R

2010-01-01

The objective of this comparative study was to evaluate effects of nitrosorbid (NS) and hydrogen sulfide-based balneotherapy (HSB) applied alone or in combination for the treatment of patients presenting with angina of effort. It was shown that long-term HSB therapy enhances the anti-anginal and anti-ischemic action of NS in such patients. The authors argue that prolonged HSB-based maintenance therapy in combination with nitrates prevents habituation to these preparations and potentiates their beneficial therapeutic effect.

Impact of adherence on the outcome of antiviral therapy for chronic hepatitis C.

PubMed

Mulhall, Brian P; Younossi, Zobair

2005-01-01

Nearly 4 million people in the United States have evidence of hepatitis C infection (HCV), representing a significant cause of cirrhosis and liver cancer as well a major burden to our healthcare systems and society. Antiviral therapy can successfully eradicate HCV over the long term, potentially reducing the risk of progression and improving patients' quality of life. The currently preferred HCV treatment is a combination of pegylated interferon alfa and ribavirin, which can achieve an overall sustained viral eradication rate of 55%. The duration of this treatment is typically determined by HCV genotype and the patient's early virologic response to the antiviral regimen. Evidence has accumulated over the past few years to indicate that close adherence to the optimal antiviral regimen can enhance sustained virologic response. But optimal treatment outcomes require diligence and careful management of side effects related to combination therapy. Although reducing the dose of pegylated interferon alfa, ribavirin, or both can effectively treat side effects, suboptimal doses of this regimen, especially ribavirin, may negatively affect virologic response. An alternative strategy is to use growth factors to treat cytopenias. This strategy can obviate dose reductions while potentially improving patients' quality of life. Patient support seems especially important early after the initiation of antiviral therapy. Encouraging study findings involving the growth factors, epoetin alfa and darbepoetin alfa, suggest improved anemia and quality of life while maintaining the optimal ribavirin dose. Future work should be aimed at providing stronger evidence for the use of these "supportive products" during anti-HCV therapy. As we strive to develop better treatment options for our HCV patients, the importance of adhering to the treatment regimen continues to play a central role. Effective side effect management is crucial for the success of this treatment because adherence is negatively affected by side effects related to the antiviral regimen. By identifying and addressing the important side effects of combination therapy for HCV, adherence to treatment can be improved and optimal outcomes can be achieved.

The Effect of Orthodontic Therapy on Periodontal Health: A Review of the Literature

PubMed Central

Alfuriji, Samah; Alhazmi, Nora; Alhamlan, Nasir; Al-Ehaideb, Ali; Alruwaithi, Moatazbellah; Alkatheeri, Nasser; Geevarghese, Amrita

2014-01-01

Objectives. This review aims to evaluate the effect of orthodontic therapy on periodontal health. Data. Original articles that reported on the effect of orthodontic therapy on periodontal health were included. The reference lists of potentially relevant review articles were also sought. Sources. A literature search was conducted using the databases, Medline, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus databases for relevant studies. The search was carried out by using a combined text and the MeSH search strategies: using the key words in different combinations: “periodontal disease,” “orthodontics” and “root resorption.” This was supplemented by hand-searching in peer-reviewed journals and cross-referenced with the articles accessed. Articles published only in English language were included. Letters to the Editor, historical reviews and unpublished articles were not sought. Conclusions. Within the limitations of the present literature review, it was observed that there is a very close inter-relationship between the periodontal health and the outcome of orthodontic therapy. PMID:24991214

The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet: A comparative study of combination therapy versus monotherapy.

PubMed

Mohamed, Maha Tarek; Abuelezz, Sally A; Atalla, Suzi Sobhy; El Aziz, Lobna Fouad Abd; Gorge, Sonia Salib

2017-05-01

Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD). 60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy. OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFα, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the mono-therapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy. Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In vitro and in vivo studies of the combination of IGF1R inhibitor figitumumab (CP-751,871) with HER2 inhibitors trastuzumab and neratinib.

PubMed

Chakraborty, Ashok K; Zerillo, Cynthia; DiGiovanna, Michael P

2015-08-01

The insulin-like growth factor I receptor (IGF1R) has been linked to resistance to HER2-directed therapy with trastuzumab (Herceptin). We examined the anti-tumor activity of figitumumab (CP-751,871), a human monoclonal antibody that blocks IGF1R ligand binding, alone and in combination with the therapeutic anti-HER2 antibody trastuzumab and the pan-HER family tyrosine kinase inhibitor neratinib, using in vitro and in vivo breast cancer model systems. In vitro assays of proliferation, apoptosis, and signaling, and in vivo anti-tumor experiments were conducted in HER2-overexpressing (BT474) and HER2-normal (MCF7) models. We find single-agent activity of the HER2-targeting drugs but not figitumumab in the BT474 model, while the reverse is true in the MCF7 model. However, in both models, combining figitumumab with HER2-targeting drugs shows synergistic anti-proliferative and apoptosis-inducing effects, and optimum inhibition of downstream signaling. In murine xenograft models, synergistic anti-tumor effects were observed in the HER2-normal MCF7 model for the combination of figitumumab with trastuzumab, and, in the HER2-overexpressing BT474 model, enhanced anti-tumor effects were observed for the combination of figitumumab with either trastuzumab or neratinib. Analysis of tumor extracts from the in vivo experiments showed evidence of the most optimal inhibition of downstream signaling for the drug combinations over the single-agent therapies. These results suggest promise for such combinations in treating patients with breast cancer, and that, unlike the case for single-agent therapy, the therapeutic effects of such combinations may be independent of expression levels of the individual receptors or the single-agent activity profile.

Roles of p38 and JNK protein kinase pathways activated by compound cantharidin capsules containing serum on proliferation inhibition and apoptosis of human gastric cancer cell line

PubMed Central

Sun, Yonghao; Zhang, Dejuan; Mao, Mao; Lu, Yangping; Jiao, Ning

2017-01-01

The aim of the present study was to investigate the inhibitory effect of compound cantharides capsules (CCCs) on the viability and apoptosis of human gastric cancer cell lines, BGC-823 and SGC-7901, and to detect its regulation of gene expression levels, as well as its inhibition mechanisms. Each cell line was grouped into a control group, CCC serum group, 5-fluorouracil (5-FU) group, combination therapy group (CCC serum + 5-FU) and serum control group. Growth curves were measured and flow cytometry was used to detect cell apoptosis and cell viability. The mRNA expression level of proliferation-related C-MYC and p53 genes were assayed by reverse transcription-quantitative polymerase chain reaction. Protein phosphorylation levels of proliferating cell nuclear antigen, p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, c-Jun N-terminal kinase (JNK) and IκB were assayed by western blotting. The combined CCC serum and 5-FU group exhibited a higher inhibition rate in both cell lines and CCC serum therapy demonstrated a similar effect to 5-FU treatment, as demonstrated in the MTT and cell growth assay. Combined therapy significantly decreased the C-MYC mRNA expression levels and increased p53 mRNA expression levels (P<0.05). Combined therapy of 5-FU and CCC was more significant compared with CCC serum or 5-FU only (P<0.05). P38 and JNK-related protein phosphorylation are involved in apoptosis initiated by CCC combined 5-FU therapy. Combined therapy was able to significantly inhibit human gastric cancer cell growth (P<0.05), and advance cell apoptosis compared with CCC serum only. CCC serum resulted in downregulation of the c-Myc gene and upregulation of the p53 gene. p38 and JNK-related protein phosphorylation is involved in the inhibition of cell viability and apoptosis of human gastric cancer cell lines. PMID:28810654

Roles of p38 and JNK protein kinase pathways activated by compound cantharidin capsules containing serum on proliferation inhibition and apoptosis of human gastric cancer cell line.

PubMed

Sun, Yonghao; Zhang, Dejuan; Mao, Mao; Lu, Yangping; Jiao, Ning

2017-08-01

The aim of the present study was to investigate the inhibitory effect of compound cantharides capsules (CCCs) on the viability and apoptosis of human gastric cancer cell lines, BGC-823 and SGC-7901, and to detect its regulation of gene expression levels, as well as its inhibition mechanisms. Each cell line was grouped into a control group, CCC serum group, 5-fluorouracil (5-FU) group, combination therapy group (CCC serum + 5-FU) and serum control group. Growth curves were measured and flow cytometry was used to detect cell apoptosis and cell viability. The mRNA expression level of proliferation-related C-MYC and p53 genes were assayed by reverse transcription-quantitative polymerase chain reaction. Protein phosphorylation levels of proliferating cell nuclear antigen, p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, c-Jun N-terminal kinase (JNK) and IκB were assayed by western blotting. The combined CCC serum and 5-FU group exhibited a higher inhibition rate in both cell lines and CCC serum therapy demonstrated a similar effect to 5-FU treatment, as demonstrated in the MTT and cell growth assay. Combined therapy significantly decreased the C-MYC mRNA expression levels and increased p53 mRNA expression levels (P<0.05). Combined therapy of 5-FU and CCC was more significant compared with CCC serum or 5-FU only (P<0.05). P38 and JNK-related protein phosphorylation are involved in apoptosis initiated by CCC combined 5-FU therapy. Combined therapy was able to significantly inhibit human gastric cancer cell growth (P<0.05), and advance cell apoptosis compared with CCC serum only. CCC serum resulted in downregulation of the c-Myc gene and upregulation of the p53 gene. p38 and JNK-related protein phosphorylation is involved in the inhibition of cell viability and apoptosis of human gastric cancer cell lines.

Escalated regeneration in sciatic nerve crush injury by the combined therapy of human amniotic fluid mesenchymal stem cells and fermented soybean extracts, Natto.

PubMed

Pan, Hung-Chuan; Yang, Dar-Yu; Ho, Shu-Peng; Sheu, Meei-Ling; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

2009-08-23

Attenuation of inflammatory cell deposits and associated cytokines prevented the apoptosis of transplanted stem cells in a sciatic nerve crush injury model. Suppression of inflammatory cytokines by fermented soybean extracts (Natto) was also beneficial to nerve regeneration. In this study, the effect of Natto on transplanted human amniotic fluid mesenchymal stem cells (AFS) was evaluated. Peripheral nerve injury was induced in SD rats by crushing a sciatic nerve using a vessel clamp. Animals were categorized into four groups: Group I: no treatment; Group II: fed with Natto (16 mg/day for 7 consecutive days); Group III: AFS embedded in fibrin glue; Group IV: Combination of group II and III therapy. Transplanted AFS and Schwann cell apoptosis, inflammatory cell deposits and associated cytokines, motor function, and nerve regeneration were evaluated 7 or 28 days after injury. The deterioration of neurological function was attenuated by AFS, Natto, or the combined therapy. The combined therapy caused the most significantly beneficial effects. Administration of Natto suppressed the inflammatory responses and correlated with decreased AFS and Schwann cell apoptosis. The decreased AFS apoptosis was in line with neurological improvement such as expression of early regeneration marker of neurofilament and late markers of S-100 and decreased vacuole formation. Administration of either AFS, or Natto, or combined therapy augmented the nerve regeneration. In conclusion, administration of Natto may rescue the AFS and Schwann cells from apoptosis by suppressing the macrophage deposits, associated inflammatory cytokines, and fibrin deposits.

Aliskiren therapy in hypertension and cardiovascular disease: a systematic review and a meta-analysis

PubMed Central

Fu, Shufang; Wen, Xin; Han, Fei; Long, Yin; Xu, Gaosi

2017-01-01

The efficacy and safety of aliskiren combination therapy with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in patients with hypertension and cardiovascular disease remains attractive attention. We searched the Cochrane Central Register, the Clinical Trials Registry, EMBASE, MEDLINE and PubMed for relevant literatures up to January 2017. A total of 13 randomized controlled trials (RCTs) with 12222 patients were included in this study, and the combined results indicated that aliskiren in combination therapy with ACEIs or ARBs had remarkable effects in reducing systolic blood pressure (SBP) [weighted mean differences (WMD), -4.20; 95% confidential intervals (CI) -5.44 to -2.97; I2, 29.7%] and diastolic blood pressure (DBP: WMD, -2.09; 95% CI -2.90 to -1.27; I2, 0%) when compared with ACEIs or ARBs monotherapy, but with significantly increased the risk of hyperkalaemia [relative risk (RR), 1.45; 95% CI 1.28 to 1.64; I2,10.6 %] and kidney injury ( RR, 1.92; 95% CI 1.14 to 3.21; I2, 0%). Besides, there was no significant difference in the incidence of major cardiovascular events (RR, 0.95; 95% CI 0.89 to 1.02; I2, 0%) between the combined therapy and ACEIs or ARBs monotherapy. In conclusion, this meta-analysis demonstrated that aliskiren in combination therapy with ACEs/ARBs could control BP effectively, but is associated with increasing risks of hyperkalaemia and kidney injury, and have no benefit in preventing of major cardiovascular events. PMID:29179525

Trial of Music, Sucrose, and Combination Therapy for Pain Relief during Heel Prick Procedures in Neonates.

PubMed

Shah, Swapnil R; Kadage, Shahajahan; Sinn, John

2017-11-01

To compare the effectiveness of music, oral sucrose, and combination therapy for pain relief in neonates undergoing a heel prick procedure. This randomized, controlled, blinded crossover clinical trial included stable neonates >32 weeks of postmenstrual age. Each neonate crossed over to all 3 interventions in random order during consecutive heel pricks. A video camera on mute mode recorded facial expressions, starting 2 minutes before until 7 minutes after the heel prick. The videos were later analyzed using the Premature Infant Pain Profile-Revised (PIPP-R) scale once per minute by 2 independent assessors, blinded to the intervention. The PIPP-R scores were compared between treatment groups using Friedman test. For the 35 participants, the postmenstrual age was 35 weeks (SD, 2.3) with an average weight of 2210 g (SD, 710). The overall median PIPP-R scores following heel prick over 6 minutes were 4 (IQR 0-6), 3 (IQR 0-6), and 1 (IQR 0-3) for the music, sucrose, and combination therapy interventions, respectively. The PIPP-R scores were significantly lower at all time points after combination therapy compared with the groups given music or sucrose alone. There was no difference in PIPP-R scores between the music and sucrose groups. In relatively stable and mature neonates, the combination of music therapy with sucrose provided better pain relief during heel prick than when sucrose or music was used alone. Recorded music in isolation had a similar effect to the current gold standard of oral sucrose. www.anzctr.org.au ACTRN12615000271505. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in serum hepatitis C virus RNA in interferon nonresponders retreated with interferon plus ribavirin: a preliminary report.

PubMed

Nyberg, L; Albrecht, J; Glue, P; Gianelli, G; Zambas, D; Elliot, M; Conrad, A; McHutchison, J

1999-06-01

Ribavirin, a nucleoside analogue, inhibits replication of RNA and DNA viruses and may control hepatitis C virus (HCV) infection through modulation of anti-inflammatory and antiviral actions. Ribavirin monotherapy has no effect on serum HCV RNA levels. In combination with interferon, this agent appears to enhance the efficacy of interferon. The aim of this study was to monitor serum HCV RNA levels early during therapy with interferon and ribavirin compared with that previously seen in the same patients during interferon monotherapy. Five patients who previously showed no response to therapy with interferon alfa 3 MU three times weekly for 6 months were retreated with the identical dose of interferon alfa 2b in combination with oral ribavirin 1,000 mg/day. Serum HCV RNA levels were monitored at baseline, week 4, week 8, and week 12 of therapy by a quantitative multicycle polymerase chain reaction assay. In the first 8 to 12 weeks, serum HCV RNA levels showed a greater decrease in all patients when retreated with combination therapy compared with interferon alone. Mean (+/- SEM) serum HCV RNA levels for interferon therapy alone were 3.3 +/- 0.95, 1.2 +/- 0.95, 1.6 +/- 1.2, and 2.3 +/- 1.2 x 10(6) copies/ml at week 0, 4, 8, and 12, respectively. This was compared with 3.3 +/- 0.83, 0.3 +/- 0.2, 0.03 +/- 0.02, and 0.15 +/- 0.14 x 10(6), respectively, for the interferon and ribavirin group (p < 0.07 at week 8). Two of five patients had undetectable serum HCV RNA during combination therapy. Combination therapy with interferon and ribavirin in prior interferon nonresponders reduces serum HCV RNA levels compared with interferon alone. This may suggest some additional antiviral effect of ribavirin when given with interferon.

Molecularly targeted therapies for malignant glioma: rationale for combinatorial strategies

PubMed Central

Thaker, Nikhil G; Pollack, Ian F

2010-01-01

Median survival of patients with malignant glioma (MG) from time of diagnosis is approximately 1 year, despite surgery, irradiation and conventional chemotherapy. Improving patient outcome relies on our ability to develop more effective therapies that are directed against the unique molecular aberrations within a patient’s tumor. Such molecularly targeted therapies may provide novel treatments that are more effective than conventional chemotherapeutics. Recently developed therapeutic strategies have focused on targeting several core glioma signaling pathways, including pathways mediated by growth-factors, PI3K/Akt/PTEN/mTOR, Ras/Raf/MEK/MAPK and other vital pathways. However, given the molecular diversity, heterogeneity and diverging and converging signaling pathways associated with MG, it is unlikely that any single agent will have efficacy in more than a subset of tumors. Overcoming these therapeutic barriers will require multiple agents that can simultaneously inhibit these processes, providing a rationale for combination therapies. This review summarizes the currently implemented single-agent and combination molecularly targeted therapies for MG. PMID:19951140

Advantages and Disadvantages of Combined Chemotherapy with Carmustine Wafer and Bevacizumab in Patients with Newly Diagnosed Glioblastoma: A Single-Institutional Experience.

PubMed

Akiyama, Yukinori; Kimura, Yuusuke; Enatsu, Rei; Mikami, Takeshi; Wanibuchi, Masahiko; Mikuni, Nobuhiro

2018-05-01

To retrospectively determine the safety and efficacy of combined chemotherapy with carmustine (BCNU) wafer, bevacizumab, and temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma (GBM). A total of 54 consecutive newly diagnosed GBMs were resected at our institution between 2010 and 2016. Twenty-nine patients underwent BCNU wafer implantation into the resection cavity followed by standard radiochemotherapy with temozolomide (TMZ, Stupp regimen) plus additional bevacizumab treatment between 2013 and 2016. Twenty-five patients who underwent resection without BCNU implantation between 2010 and 2012 were enrolled as a control group; these patients were treated with the Stupp regimen and did not receive bevacizumab. This retrospective study included evaluation of progression-free survival and overall survival, plus comparisons between the combined therapy group and the control group. There were no significant differences in age, sex, Karnofsky Performance Status on admission, isocitrate dehydrogenase 1/2 mutation ratio, or resection rate between the combined and standard therapy groups. The median overall survival in the combined therapy group and control group was 24.2 months and 15.30, respectively (P = 0.027). The median progression-free survival was 16.8 months and 7.30 months, respectively (P = 0.009). Overall, the incidence of adverse events leading to discontinuation of the study drug was similar between the treatment groups, except for infection, which was more common in the combined treatment group and required repeat surgery. The combined therapy showed higher efficacy compared with standard therapy in patients with GBM. Therefore, combined therapy seems to be effective with an acceptable toxicity profile. Copyright © 2018 Elsevier Inc. All rights reserved.

[Therapeutic effect of rmIL-12 combined with G-CSF on acute radiation sickness produced by γ-ray irradiation in mice].

PubMed

Wang, Li; Zhai, Rui-Ren; Pang, Zhao-Xia; Zhang, Chao; Yu, Chang-Lin

2012-08-01

The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G-CSF can significantly accelerate the recovery of hematopoietic function in mice with acute radiation sickness.

Gene therapy in pancreatic cancer

PubMed Central

Liu, Si-Xue; Xia, Zhong-Sheng; Zhong, Ying-Qiang

2014-01-01

Pancreatic cancer (PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC. This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website (http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property. Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras, anti-angiogenesis gene VEGFR, suicide gene HSK-TK, cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiotherapy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC. PMID:25309069

Lineage plasticity-mediated therapy resistance in prostate cancer.

PubMed

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Antiosteoporotic Effect of Combined Extract of Morus alba and Polygonum odoratum

PubMed Central

Sungkamanee, Sudarat; Thukham-mee, Wipawee

2014-01-01

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

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy.

PubMed

Gheorghe, Liana; Cotruta, Bogdan; Trifu, Viorel; Cotruta, Cristina; Becheanu, Gabriel; Gheorghe, Cristian

2008-09-01

Pegylated interferon-alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweet's syndrome in association with pegylated interferon-alpha therapy.

Rejuvenation of the Aging Arm: Multimodal Combination Therapy for Optimal Results.

PubMed

Wu, Douglas C; Green, Jeremy B

2016-05-01

The aging arm is characterized by increased dyspigmentation, a proliferation of ectactic blood vessels, excessive adiposity, excessive skin laxity, and actinic keratosis. A variety of laser, energy, and surgical techniques can be used to improve these features. The objective of this article is to describe the treatment modalities that have proven efficacious in rejuvenating the aging arm and combination therapies that have the potential to optimize patient outcomes while maintaining safety and tolerability. A Medline search was performed on nonsurgical aesthetic combination treatments because it relates to arm rejuvenation, and results are summarized. Practical applications for these combination treatments are also discussed. Although there is significant evidence supporting the effective use of nonsurgical treatments for arm rejuvenation, little in the literature was found on the safety and efficacy of combining such procedures and devices. However, in the authors' clinical experience, combining arm rejuvenation techniques can be done safely and often result in optimal outcomes. Arm rejuvenation can be safely and effectively achieved with combination nonsurgical aesthetic treatments.

Radio-photothermal therapy mediated by a single compartment nanoplatform depletes tumor initiating cells and reduces lung metastasis in the orthotopic 4T1 breast tumor model

NASA Astrophysics Data System (ADS)

Zhou, Min; Zhao, Jun; Tian, Mei; Song, Shaoli; Zhang, Rui; Gupta, Sanjay; Tan, Dongfeng; Shen, Haifa; Ferrari, Mauro; Li, Chun

2015-11-01

Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy.Tumor Initiating Cells (TICs) are resistant to radiotherapy and chemotherapy, and are believed to be responsible for tumor recurrence and metastasis. Combination therapies can overcome the limitation of conventional cancer treatments, and have demonstrated promising application in the clinic. Here, we show that dual modality radiotherapy (RT) and photothermal therapy (PTT) mediated by a single compartment nanosystem copper-64-labeled copper sulfide nanoparticles ([64Cu]CuS NPs) could suppress breast tumor metastasis through eradication of TICs. Positron electron tomography (PET) imaging and biodistribution studies showed that more than 90% of [64Cu]CuS NPs was retained in subcutaneously grown BT474 breast tumor 24 h after intratumoral (i.t.) injection, indicating the NPs are suitable for the combination therapy. Combined RT/PTT therapy resulted in significant tumor growth delay in the subcutaneous BT474 breast cancer model. Moreover, RT/PTT treatment significantly prolonged the survival of mice bearing orthotopic 4T1 breast tumors compared to no treatment, RT alone, or PTT alone. The RT/PTT combination therapy significantly reduced the number of tumor nodules in the lung and the formation of tumor mammospheres from treated 4T1 tumors. No obvious side effects of the CuS NPs were noted in the treated mice in a pilot toxicity study. Taken together, our data support the feasibility of a therapeutic approach for the suppression of tumor metastasis through localized RT/PTT therapy. Electronic supplementary information (ESI) available: Details of methods used for radiolabeling efficiency and stability of 64Cu-labeled CuS NPs. See DOI: 10.1039/c5nr04587h

Effectiveness of cognitive-behavioral group therapy for patients with hypochondriasis (health anxiety).

PubMed

Weck, Florian; Gropalis, Maria; Hiller, Wolfgang; Bleichhardt, Gaby

2015-03-01

Cognitive behavioral therapy (CBT) has been shown to be highly effective in the treatment of health anxiety. However, little is known about the effectiveness of group CBT in the treatment of health anxiety. The current study is the largest study that has investigated the effectiveness of combined individual and group CBT for patients with the diagnosis of hypochondriasis (N=80). Therapy outcomes were evaluated by several questionnaires. Patients showed a large improvement on these primary outcome measures both post-treatment (Cohen's d=0.82-1.08) and at a 12-month follow-up (Cohen's d=1.09-1.41). Measures of general psychopathology and somatic symptoms showed significant improvements, with small to medium effect sizes. Patients with more elevated hypochondriacal characteristics at therapy intake showed a larger therapy improvement, accounting for 7-8% of the variance in therapy outcome. CBT group therapy has therefore been shown to be an appropriate and cost-effective treatment for health anxiety. Copyright © 2015 Elsevier Ltd. All rights reserved.

"Smart" nickel oxide based core-shell nanoparticles for combined chemo and photodynamic cancer therapy.

PubMed

Bano, Shazia; Nazir, Samina; Munir, Saeeda; AlAjmi, Mohamed Fahad; Afzal, Muhammad; Mazhar, Kehkashan

2016-01-01

We report "smart" nickel oxide nanoparticles (NOPs) as multimodal cancer therapy agent. Water-dispersible and light-sensitive NiO core was synthesized with folic acid (FA) connected bovine serum albumin (BSA) shell on entrapped doxorubicin (DOX). The entrapped drug from NOP-DOX@BSA-FA was released in a sustained way (64 hours, pH=5.5, dark conditions) while a robust release was found under red light exposure (in 1/2 hour under λmax=655 nm, 50 mW/cm(2), at pH=5.5). The cell viability, thiobarbituric acid reactive substances and diphenylisobenzofuran assays conducted under light and dark conditions revealed a high photodynamic therapy potential of our construct. Furthermore, we found that the combined effect of DOX and NOPs from NOP-DOX@BSA-FA resulted in cell death approximately eightfold high compared to free DOX. We propose that NOP-DOX@BSA-FA is a potential photodynamic therapy agent and a collective drug delivery system for the systemic administration of cancer chemotherapeutics resulting in combination therapy.

What interventions can improve quality of life or psychosocial factors of individuals with knee osteoarthritis? A systematic review with meta-analysis of primary outcomes from randomised controlled trials.

PubMed

Briani, Ronaldo Valdir; Ferreira, Amanda Schenatto; Pazzinatto, Marcella Ferraz; Pappas, Evangelos; De Oliveira Silva, Danilo; Azevedo, Fábio Mícolis de

2018-03-16

To systematically review evidence of primary outcomes from randomised controlled trials (RCTs) examining the effect of treatment strategies on quality of life (QoL) or psychosocial factors in individuals with knee osteoarthritis (OA). Systematic review with meta-analysis. Medline, Embase, SPORTDiscus, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science were searched from inception to November 2017. We included RCTs investigating the effect of conservative interventions on QoL or psychosocial factors in individuals with knee OA. Only RCTs considering these outcomes as primary were included. Pooled data supported the use of exercise therapy compared with controls for improving health-related and knee-related QoL. There was limited evidence that a combined treatment of yoga, transcutaneous electrical stimulation and ultrasound may be effective in improving QoL. Limited evidence supported the use of cognitive behavioural therapies (with or without being combined with exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress. Exercise therapy (with or without being combined with other interventions) seems to be effective in improving health-related and knee-related QoL or psychosocial factors of individuals with knee OA. In addition, evidence supports the use of cognitive behavioural therapies (with or without exercise therapy) for improving psychosocial factors such as self-efficacy, depression and psychological distress in individuals with knee OA. CRD42016047602. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recent Advances in Cancer Therapy Based on Dual Mode Gold Nanoparticles

PubMed Central

Spyratou, Ellas; Makropoulou, Mersini; Sihver, Lembit

2017-01-01

Many tumor-targeted strategies have been used worldwide to limit the side effects and improve the effectiveness of therapies, such as chemotherapy, radiotherapy (RT), etc. Biophotonic therapy modalities comprise very promising alternative techniques for cancer treatment with minimal invasiveness and side-effects. These modalities use light e.g., laser irradiation in an extracorporeal or intravenous mode to activate photosensitizer agents with selectivity in the target tissue. Photothermal therapy (PTT) is a minimally invasive technique for cancer treatment which uses laser-activated photoabsorbers to convert photon energy into heat sufficient to induce cells destruction via apoptosis, necroptosis and/or necrosis. During the last decade, PTT has attracted an increased interest since the therapy can be combined with customized functionalized nanoparticles (NPs). Recent advances in nanotechnology have given rise to generation of various types of NPs, like gold NPs (AuNPs), designed to act both as radiosensitizers and photothermal sensitizing agents due to their unique optical and electrical properties i.e., functioning in dual mode. Functionalized AuNPS can be employed in combination with non-ionizing and ionizing radiation to significantly improve the efficacy of cancer treatment while at the same time sparing normal tissues. Here, we first provide an overview of the use of NPs for cancer therapy. Then we review many recent advances on the use of gold NPs in PTT, RT and PTT/RT based on different types of AuNPs, irradiation conditions and protocols. We refer to the interaction mechanisms of AuNPs with cancer cells via the effects of non-ionizing and ionizing radiations and we provide recent existing experimental data as a baseline for the design of optimized protocols in PTT, RT and PTT/RT combined treatment. PMID:29257070

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Parathyroid hormone plus alendronate in osteoporosis: a meta-analysis of randomized controlled trials.

PubMed

Zhang, Qinggang; Qian, Jing; Zhu, Yuchang

2015-01-01

Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy of PTH with alendronate will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy of PTH with alendronate in the treatment of patients with osteoporosis. A comprehensive literature search of PubMed, Embase, and Web of Science was conducted to identify relative studies. Eligible studies were randomized controlled trials (RCT), which assessed the efficacy of combination therapy in patients with osteoporosis. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using of random-effects or fixed-effects model, depending on the heterogeneity between the included studies. Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy of PTH with alendronate resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95% CI: 1.58, 3.31; P = 0.000), but not in lumbar spine (WMD = -0.83, 95% CI: -3.48, 1.81; P = 0.538), femoral neck (WMD = -0.99, 95% CI: -2.04, 0.07; P = 0.068), and total hip (WMD = -0.06, 95% CI: -0.93, 0.81; P = 0.892). The subgroup analysis based on the dosage and schedule of PTH, study duration, gender of patients, and anabolic agents, were conducted. And results revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 μg (WMD = 2.33, 95% CI: 1.24, 3.43; P = 0.000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95% CI: 1.00, 3.47; P = 0.000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95% CI: 0.63, 2.53; P = 0.001). However, the combination of PTH of 40 μg with alendronate produced a decrease in the BMD at spine (WMD = -4.56, 95% CI: -7.56, -1.56; P = 0.003) and femoral neck (WMD = -5.82, 95% CI: -9.91, -1.72; P = 0.005). Our findings indicated that the addition of alendronate to PTH in the treatment of osteoporosis, reduced the ability of PTH therapy to increase the BMD at the lumbar spine, femoral neck, and total hip.

[Clinical observation of basic fibroblast growth factor combined with topical oxygen therapy in enhancing burn wound healing].

PubMed

Nie, Kaiyu; Li, Pengcheng; Zeng, Xueqin; Sun, Guangfeng; Jin, Wenhu; Wei, Zairong; Wang, Bo; Qi, Jianping; Wang, Yuming; Wang, Dali

2010-06-01

To investigate the efficacy of basic fibroblast growth factor (bFGF) combined with topical oxygen therapy for deep II degree burn wounds, by comparing the effects of bFGF combined with topical oxygen therapy and bFGF with routine therapy. From February 2004 to July 2009, 85 patients with deep II degree burn wounds (117 wounds) were enrolled and divided into 4 groups randomly according to different treatments. There was no significant difference in sex, age, disease course, wound size, and wound treatment size among 4 groups (P > 0.05). In group A, 18 patients (28 wounds) were treated routinely; in group B, 23 patients (30 wounds) were treated with routine methods and topical oxygen therapy; in group C, 19 patients (25 wounds) were treated with routine methods and bFGF therapy; and in group D, 25 patients (34 wounds) were treated with routine methods and bFGF/topical oxygen therapy. Topical oxygen therapy was administered to the wound for 90 minutes per day for 3 weeks. The bFGF therapy was applied everyday (150 U/cm2) for 3 weeks. All cases were followed up 6-12 months (9 months on average). The wound healing times in groups A, B, C, and D were (27.3 +/- 6.6), (24.2 +/- 5.8), (22.2 +/- 6.8), and (18.2 +/- 4.8) days, respectively; showing significant difference between group A and group D (P < 0.05). The wound healing rates in groups A, B, C, and D were 67.8% +/- 12.1%, 85.1% +/- 7.5%, 89.2% +/- 8.3%, and 96.1% +/- 5.6%, respectively; showing significant differences between group A and groups B, C, D (P < 0.05). The therapic effective rates in groups A, B, C, and D were 75%, 90%, 92%, and 100%, respectively; showing significant difference between group A and group D (P < 0.05). The Vancouver scar scale scoring of group D 6 months after treatment was better than that of group A (P < 0.05). The bFGF combined with topical oxygen therapy can enhance deep II degree burn wound healing. Furthermore, the therapy method is simple and convenient.

Effect of speech therapy as adjunct treatment to continuous positive airway pressure on the quality of life of patients with obstructive sleep apnea.

PubMed

Diaferia, Giovana; Badke, Luciana; Santos-Silva, Rogerio; Bommarito, Silvana; Tufik, Sergio; Bittencourt, Lia

2013-07-01

Patients with obstructive sleep apnea (OSA) exhibit reduced quality of life (QoL) due to their daytime symptoms that restricted their social activities. The available data for QoL after treatment with continuous positive airway pressure (CPAP) are inconclusive, and few studies have assessed QoL after treatment with speech therapy or other methods that increase the tonus of the upper airway muscles or with a combination of these therapies. The aim of our study was to assess the effect of speech therapy alone or combined with CPAP on QoL in patients with OSA using three different questionnaires. Men with OSA were randomly allocated to four treatment groups: placebo, 24 patients had sham speech therapy; speech therapy, 27 patients had speech therapy; CPAP, 27 patients had treatment with CPAP; and combination, 22 patients had treatment with CPAP and speech therapy. All patients were treated for 3 months. Participants were assessed before and after treatment and after 3 weeks of a washout period using QoL questionnaires (Functional Outcomes of Sleep Questionnaire [FOSQ], World Health Organization Quality of Life [WHOQoL-Bref], and Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]). Additional testing measures included an excessive sleepiness scale (Epworth sleepiness scale [ESS]), polysomnography (PSG), and speech therapy assessment. A total of 100 men aged 48.1±11.2 (mean±standard deviation) years had a body mass index (BMI) of 27.4±4.9 kg/m(2), an ESS score of 12.7±3.0, and apnea-hypopnea index (AHI) of 30.9±20.6. After treatment, speech therapy and combination groups showed improvement in the physical domain score of the WHOQoL-Bref and in the functional capacity domain score of the SF-36. Our results suggest that speech therapy alone as well as in association with CPAP might be an alternative treatment for the improvement of QoL in patients with OSA. Copyright © 2013 Elsevier B.V. All rights reserved.

Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1985,

DTIC Science & Technology

1985-10-01

Pavia AT, Lozner EC: Sex Hormones and Coronary Artery Disease in Men. Clin Res 33(2):246, 1985. Friedl KE, Plymate SR: Effect of Obesity on Reproduction...Department of Pediatrics (Cont) Moore DC: Combination Therapy in an Adolescent with Polycystic Ovaries, Hirsutism, Type-A Insulin Resistance , and Acanthosis...Suppression of Hirsutism with Combination Therapy in an Adoles- cent with Insulin Resistance and Acanthosis Nigricans. Submitted NEJM, Au, 1985

Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy.

PubMed

Lecumberri, Elena; Dupertuis, Yves Marc; Miralbell, Raymond; Pichard, Claude

2013-12-01

Green tea catechins, especially epigallocatechin-3-gallate (EGCG), have been associated with cancer prevention and treatment. This has resulted in an increased number of studies evaluating the effects derived from the use of this compound in combination with chemo/radiotherapy. This review aims at compiling latest literature on this subject. Keywords including EGCG, cancer, chemotherapy, radiotherapy and side effects, were searched using PubMed and ScienceDirect databases to identify, analyze, and summarize the research literature on this topic. Most of the studies on this subject up to date are preclinical. Relevance of the findings, impact factor, and date of publication were critical parameters for the studies to be included in the review. Additive and synergistic effects of EGCG when combined with conventional cancer therapies have been proposed, and its anti-inflammatory and antioxidant activities have been related to amelioration of cancer therapy side effects. However, antagonistic interactions with certain anticancer drugs might limit its clinical use. The use of EGCG could enhance the effect of conventional cancer therapies through additive or synergistic effects as well as through amelioration of deleterious side effects. Further research, especially at the clinical level, is needed to ascertain the potential role of EGCG as adjuvant in cancer therapy. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Photodynamic Therapy with Hypericin Improved by Targeting HSP90 Associated Proteins

PubMed Central

Solár, Peter; Chytilová, Mária; Solárová, Zuzana; Mojžiš, Ján; Ferenc, Peter; Fedoročko, Peter

2011-01-01

In this study we have focused on the response of SKBR-3 cells to both single 17-DMAG treatment as well as its combination with photodynamic therapy with hypericin. Low concentrations of 17-DMAG without any effect on survival of SKBR-3 cells significantly reduced metabolic activity, viability and cell number when combined with photodynamic therapy with hypericin. Moreover, IC10 concentation of 17-DMAG resulted in significant increase of SKBR-3 cells in G1 phase of the cell cycle, followed by an increase of cells in G2 phase when combined with photodynamic therapy. Furthermore, 17-DMAG already decreased HER2, Akt, P-Erk1/2 and survivin protein levels in SKBR-3 cells a short time after its application. In this regard, 17-DMAG protected also SKBR-3 cells against both P-Erk1/2 as well as survivin upregulations induced by photodynamic therapy with hypericin. Interestingly, IC10 concentration of 17-DMAG led to total depletion of Akt, P-Erk1/2 proteins and to decrease of survivin level at 48 h. On the other hand, 17-DMAG did not change HER2 relative expression in SKBR-3 cells, but caused a significant decrease of HER2 mRNA in MCF-7 cells characterized by low HER2 expression. These results show that targeting HSP90 client proteins increases the efficiency of antineoplastic effect of photodynamic therapy in vitro. PMID:27721334

Metastatic Thymoma-Associated Myasthenia Gravis: Favorable Response to Steroid Pulse Therapy Plus Immunosuppressive Agent

PubMed Central

Qi, Guoyan; Liu, Peng; Dong, Huimin; Gu, Shanshan; Yang, Hongxia; Xue, Yinping

2017-01-01

Background Our study retrospectively reviewed the therapeutic effect of steroid pulse therapy in combination with an immunosuppressive agent in myasthenia gravis (MG) patients with metastatic thymoma. Material/Methods MG patients with metastatic thymoma that underwent methylprednisolone pulse therapy plus cyclophosphamide were retrospectively analyzed. Patients initially received methylprednisolone pulse therapy followed by oral methylprednisolone. Cyclophosphamide was prescribed simultaneously at the beginning of treatment. Clinical outcomes, including therapeutic efficacy and adverse effects of MG and thymoma, were assessed. Results Twelve patients were recruited. According to histological classification, 4 cases were type B2 thymoma, 3 were type B3, 2 were type B1, and 1 was type AB. After combined treatment for 15 days, both the thymoma and MG responded dramatically to high-dose methylprednisolone plus cyclophosphamide. The symptoms of MG were improved in all patients, with marked improvement in 6 patients and basic remission in 4. Interestingly, complete remission of thymoma was achieved in 5 patients and partial remission in 7 patients. Myasthenic crisis was observed in 1 patient and was relieved after intubation and ventilation. Adverse reactions were observed in 7 patients (58.3%), most commonly infections, and all were resolved without discontinuation of therapy. During the follow-up, all patients were stabilized except for 1 with pleural metastasis who received further treatment and another 1 who died from myasthenic crisis. Conclusions The present study in a series of MG patients with metastatic thymoma indicated that steroid pulse therapy in combination with immunosuppressive agents was an effective and well-tolerated for treatment of both metastatic thymoma and MG. Glucocorticoid pulse therapy plus immunosuppressive agents should therefore be considered in MG patients with metastatic thymoma. PMID:28278141

Efficacy and Tolerability of Nilvadipine in Combination with an Angiotensin II Receptor Antagonist in Patients with Essential Hypertension: A Multicenter, Open-Label, Uncontrolled Study

PubMed Central

Noda, Keita; Ideishi, Munehito; Tashiro, Eiichiro; Nakashima, Yoshiyuki; Imamura, Mitsuhide; Seki, Masahiko; Fujino, Masanori; Sou, Toshimitsu; Kohara, Masaki; Kanaya, Hisashi; Saku, Nishiki; Kamei, Ritsu; Yamasaki, Misao; Sakai, Hiroshi; Gondo, Naoki; Saku, Keijiro

2003-01-01

Background: Combination therapy with different classes of antihypertensive drugs often is needed to achieve controlled blood pressure (BP). The combination of an angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred option for reducing uncontrolled BP. Objective: The aim of this study was to assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine calcium antagonist, in combination with an AIIA. Methods: Patients with essential hypertension whose BP was not controlled by an AIIA alone were eligible for this multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This combination therapy was given for 8 weeks. BP and heart rate were measured between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination therapy. Adverse events were monitored at each visit. Results: Thirty-one patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years) were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP) and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0 mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ significantly between the 3 AIIAs tested. Pulse pressure also decreased significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the percentage of patients with DBP <90 mm Hg or a decrease in DBP ≥10 mm Hg) was 72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or severe flushing, mild headache, and mild palpitation. All of these symptoms resolved after nilvadipine treatment was discontinued. Conclusions: Nilvadipine in combination with an AIIA showed good antihypertensive efficacy and was well tolerated in the hypertensive patients in this study. This combination also significantly decreased pulse pressure, suggesting that this combination therapy also may have a beneficial effect in elderly patients with isolated systolic hypertension. PMID:25053855

Cost-effectiveness of adherence therapy versus health education for people with schizophrenia: randomised controlled trial in four European countries

PubMed Central

2013-01-01

Background Non-adherence to anti-psychotics is common, expensive and affects recovery. We therefore examine the cost-effectiveness of adherence therapy for people with schizophrenia by multi-centre randomised trial in Amsterdam, London, Leipzig and Verona. Methods Participants received 8 sessions of adherence therapy or health education. We measured lost productivity and use of health/social care, criminal justice system and informal care at baseline and one year to estimate and compare mean total costs from health/social care and societal perspectives. Outcomes were the Short Form 36 (SF-36) mental component score (MCS) and quality-adjusted life years (QALYs) gained (SF-36 and EuroQoL 5 dimension (EQ5D)). Cost-effectiveness was examined for all cost and outcome combinations using cost-effectiveness acceptability curves (CEACs). Results 409 participants were recruited. There were no cost or outcome differences between adherence therapy and health education. The probability of adherence therapy being cost-effective compared to health education was between 0.3 and 0.6 for the six cost-outcome combinations at the willingness to pay thresholds we examined. Conclusions Adherence therapy appears equivalent to health education. It is unclear whether it would have performed differently against a treatment as usual control, whether such an intervention can impact on quality of life in the short-term, or whether it is likely to be cost-effective in some sites but not others. Trial registration Trial registration: Current Controlled Trials ISRCTN01816159 PMID:23705862

Manual therapy, exercise therapy, or both, in addition to usual care, for osteoarthritis of the hip or knee. 2: economic evaluation alongside a randomized controlled trial.

PubMed

Pinto, D; Robertson, M C; Abbott, J H; Hansen, P; Campbell, A J

2013-10-01

To evaluate the cost effectiveness of manual physiotherapy, exercise physiotherapy, and a combination of these therapies for patients with osteoarthritis of the hip or knee. 206 Adults who met the American College of Rheumatology criteria for hip or knee osteoarthritis were included in an economic evaluation from the perspectives of the New Zealand health system and society alongside a randomized controlled trial. Resource use was collected using the Osteoarthritis Costs and Consequences Questionnaire. Quality-adjusted life years (QALYs) were calculated using the Short Form 6D. Willingness-to-pay threshold values were based on one to three times New Zealand's gross domestic product (GDP) per capita of NZ$ 29,149 (in 2009). All three treatment programmes resulted in incremental QALY gains relative to usual care. From the perspective of the New Zealand health system, exercise therapy was the only treatment to result in an incremental cost utility ratio under one time GDP per capita at NZ$ 26,400 (-$34,081 to $103,899). From the societal perspective manual therapy was cost saving relative to usual care for most scenarios studied. Exercise therapy resulted in incremental cost utility ratios regarded as cost effective but was not cost saving. For most scenarios combined therapy was not as cost effective as the two therapies alone. In this study, exercise therapy and manual therapy were more cost effective than usual care at policy relevant values of willingness-to-pay from both the perspective of the health system and society. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12608000130369. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Synergistic Effects of NDRG2 Overexpression and Radiotherapy on Cell Death of Human Prostate LNCaP Cells.

PubMed

Alizadeh Zarei, M; Takhshid, M A; Behzad Behbahani, A; Hosseini, S Y; Okhovat, M A; Rafiee Dehbidi, Gh R; Mosleh Shirazi, M A

2017-09-01

Radiation therapy is among the most conventional cancer therapeutic modalities with effective local tumor control. However, due to the development of radio-resistance, tumor recurrence and metastasis often occur following radiation therapy. In recent years, combination of radiotherapy and gene therapy has been suggested to overcome this problem. The aim of the current study was to explore the potential synergistic effects of N-Myc Downstream-Regulated Gene 2 (NDRG2) overexpression, a newly identified candidate tumor suppressor gene, with radiotherapy against proliferation of prostate LNCaP cell line. In this study, LNCaP cells were exposed to X-ray radiation in the presence or absence of NDRG2 overexpression using plasmid PSES- pAdenoVator-PSA-NDRG2-IRES-GFP. The effects of NDRG2 overexpression, X-ray radiation or combination of both on the cell proliferation and apoptosis of LNCaP cells were then analyzed using MTT assay and flow cytometery, respectively. Results of MTT assay showed that NDRG2 overexpression and X-ray radiation had a synergistic effect against proliferation of LNCaP cells. Moreover, NDRG2 overexpression increased apoptotic effect of X-ray radiation in LNCaP cells synergistically. Our findings suggested that NDRG2 overexpression in combination with radiotherapy may be an effective therapeutic option against prostate cancer.

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

PubMed Central

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-01-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

PubMed

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-05-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

Targeted cancer therapy--are the days of systemic chemotherapy numbered?

PubMed

Joo, Won Duk; Visintin, Irene; Mor, Gil

2013-12-01

Targeted therapy or molecular targeted therapy has been defined as a type of treatment that blocks the growth of cancer cells by interfering with specific cell molecules required for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells as with traditional chemotherapy. There is a growing number of FDA approved monoclonal antibodies and small molecules targeting specific types of cancer suggestive of the growing relevance of this therapeutic approach. Targeted cancer therapies, also referred to as "Personalized Medicine", are being studied for use alone, in combination with other targeted therapies, and in combination with chemotherapy. The objective of personalized medicine is the identification of patients that would benefit from a specific treatment based on the expression of molecular markers. Examples of this approach include bevacizumab and olaparib, which have been designated as promising targeted therapies for ovarian cancer. Combinations of trastuzumab with pertuzumab, or T-DM1 and mTOR inhibitors added to an aromatase inhibitor are new therapeutic strategies for breast cancer. Although this approach has been seen as a major step in the expansion of personalized medicine, it has substantial limitations including its high cost and the presence of serious adverse effects. The Cancer Genome Atlas is a useful resource to identify novel and more effective targets, which may help to overcome the present limitations. In this review we will discuss the clinical outcome of some of these new therapies with a focus on ovarian and breast cancer. We will also discuss novel concepts in targeted therapy, the target of cancer stem cells. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Clinical effect of triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori infection in children].

PubMed

Zhao, Hong-Mei; Ou-Yang, Hong-Juan; Duan, Bo-Ping; Xu, Bin; Chen, Zhi-Yong; Tang, Juan; You, Jie-Yu

2014-03-01

To evaluate the clinical effect of proton pump inhibitor-based triple therapy combined with Saccharomyces boulardii in the treatment of Helicobacter pylori (Hp) infection among children in terms of Hp eradication rate and incidence of adverse events. A prospective randomised controlled study was conducted on 240 children with a confirmed diagnosis of Hp infection. These patients were randomized into triple therapy (n=120) and probiotics groups (n=120). The triple therapy group received amoxicillin [40 mg/(kg·d), Tid], clarithromycin [15 mg/(kg·d), Bid] and omeprazole [0.7-0.8 mg/(kg·d), Qd], while the probiotics group received Saccharomyces boulardii (250 mg, Bid) in addition to triple therapy. The course of treatment was 14 days in both groups. The adverse events in subjects were recorded by their parents during treatment. Hp eradiation was evaluated by (13)C breath test at 4 weeks after treatment, and the eradication rate and incidence of adverse events were compared between the two groups. The Hp eradication rates were 75.8% (91/120) in the triple therapy group and 85% (102/120) in the probiotics group (P>0.05). Compared with the triple therapy group, the probiotics group had nonsignificantly lower incidence of nausea, vomiting, and abdominal pain (P>0.05) and significantly lower incidence of stomatitis, constipation and diarrhea (P<0.05). Triple therapy combined with Saccharomyces boulardii cannot significantly increase Hp eradication rate, but can significantly reduce the incidence of stomatitis, constipation, and diarrhea during treatment.

The Effect of Combination Antiviral Therapy in the Treatment of Hepatitis C on the Occurrence of Depressive Disorder in Patients Treated for Hepatitis C in the Republic of Srpska.

PubMed

Banjac, Visnja; Zivlak-Radulovic, Nera; Miskovic, Mirjana

2016-04-01

The current standard treatment of chronic hepatitis C in Bosnia and Herzegovina consists of pegylated interferon alpha in combination with ribavirin. Interferon therapy has many psychiatric side effects, with depressive symptomatology being most prominent. The aim of the study was to establish the frequency and severity of depression in patients with chronic hepatitis C during two months of the aforementioned therapy. The overall sample consisted of 46 subjects, divided into three subgroups, aged 18 to 65. The study population consisted of subjects treated for chronic hepatitis C (n = 15), subjects infected but not treated for chronic hepatitis C (n = 15), and healthy controls (n = 16). The assessment and level of depression were based on the Structural clinical interview (SCID), Montgomery-Asberg Depression Rating Scale and Zung Self-Rating Depression Scale. The assessments were conducted before interferon therapy (on the day 0), after 4 and 8 weeks of therapy. Regarding its frequency, MADRS scoring showed that the number of depressed subjects receiving therapy increased after 8 weeks (46.7%). There was statistical significance between the subgroups after 4 and 8 weeks. Likewise, the ZUNG scale showed that the number of depressed subjects receiving therapy increased after 8 weeks (73.3%). There was statistical significance between the subgroups on the day 0, after 4 and 8 weeks. Depression was significantly more frequent in chronic hepatitis C subjects treated with interferon alpha in combination with ribavirin than in subjects in the group without therapy. Mild depression was most prevalent.

Increased anti-tumor effects using IL2 with anti-TGFβ reveals competition between mouse NK and CD8 T cells

PubMed Central

Alvarez, Maite; Bouchlaka, Myriam N.; Sckisel, Gail D.; Sungur, Can M.; Chen, Mingyi; Murphy, William J.

2014-01-01

Due to increasing interest in the removal of immunosuppressive pathways in cancer, the combination of IL2 with antibodies to neutralize TGFβ, a potent immunosuppressive cytokine, was assessed. Combination immunotherapy resulted in significantly greater anti-tumor effects. These were correlated with significant increases in the numbers and functionality of NK cells, NK progenitors and activated CD8 T cells resulting in the observed anti-tumor effects. Combination immunotherapy was also accompanied with lesser toxicities than IL2 therapy alone. Additionally, we observed a dual competition between NK and activated CD8 T cells such that after immunotherapy, the depletion of either effector population resulted in the increased total expansion of the other population and compensatory anti-tumor effects. This study demonstrates the efficacy of this combination immunotherapeutic regimen as a promising cancer therapy and illustrates the existence of potent competitive regulatory pathways between NK and CD8 T cells in response to systemic activation. PMID:25000978

[Changes of twenty-four-hour profile blood pressure and its correction of patients with arterial hypertension on the background of combined antihypertensive therapy application].

PubMed

Solomennchuk, T M; Slaba, N A; Prots'ko, V V; Bedzaĭ, A O

2014-01-01

The aim of this research was the study of efficiency and endurance antihypertensive therapy on the basis of fixed combination of enalapril and hydrochlorothiazide (HCTZ) and enalapril and HCTZ in combination with amlodipine according to the twenty-four-hour (? day-and-night) monitoring of blood pressure (? 24H BPM) of patients with arterial hypertension (AH) 2-3 severity. The study included 33 patients with 2-3 grade of hypertension (average age--54,40 ± 3.45 years). All patients performed ? 24H BPM before treatment and after 12 weeks of therapy. The combination of enalapril and HCTZ allowed to achieve target levels of blood pressure in 79% of patients, amlodipine additional purpose--in 86% of patients. We found that this therapy has a corrective effect on daily blood pressure profile, significantly reducing the load pressure and blood pressure variability. During treatment with the combination of enalapril and HCTZ combination of enalapril, HCTZ with amlodipine optimal daily profile of blood pressure after 12 weeks of reaching respectively 63.1% and 71.4% of patients. The treatment with combination of enalapril and HCTZ and adding of amlodipine is characterized by good endurance and high adherence to treatment.

Cost-Effectiveness of Non-Invasive and Non-Pharmacological Interventions for Low Back Pain: a Systematic Literature Review.

PubMed

Andronis, Lazaros; Kinghorn, Philip; Qiao, Suyin; Whitehurst, David G T; Durrell, Susie; McLeod, Hugh

2017-04-01

Low back pain (LBP) is a major health problem, having a substantial effect on peoples' quality of life and placing a significant economic burden on healthcare systems and, more broadly, societies. Many interventions to alleviate LBP are available but their cost effectiveness is unclear. To identify, document and appraise studies reporting on the cost effectiveness of non-invasive and non-pharmacological treatment options for LBP. Relevant studies were identified through systematic searches in bibliographic databases (EMBASE, MEDLINE, PsycINFO, Cochrane Library, CINAHL and the National Health Service Economic Evaluation Database), 'similar article' searches and reference list scanning. Study selection was carried out by three assessors, independently. Study quality was assessed using the Consensus on Health Economic Criteria checklist. Data were extracted using customized extraction forms. Thirty-three studies were identified. Study interventions were categorised as: (1) combined physical exercise and psychological therapy, (2) physical exercise therapy only, (3) information and education, and (4) manual therapy. Interventions assessed within each category varied in terms of their components and delivery. In general, combined physical and psychological treatments, information and education interventions, and manual therapies appeared to be cost effective when compared with the study-specific comparators. There is inconsistent evidence around the cost effectiveness of physical exercise programmes as a whole, with yoga, but not group exercise, being cost effective. The identified evidence suggests that combined physical and psychological treatments, medical yoga, information and education programmes, spinal manipulation and acupuncture are likely to be cost-effective options for LBP.

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

PubMed

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

2018-01-01

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

Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

PubMed

Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

2017-05-01

Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Acupuncture and Traditional Herbal Medicine Therapy Prevent Deliriumin Patients with Cardiovascular Disease in Intensive Care Units.

PubMed

Matsumoto-Miyazaki, Jun; Ushikoshi, Hiroaki; Miyata, Shusaku; Miyazaki, Nagisa; Nawa, Takahide; Okada, Hideshi; Ojio, Shinsuke; Ogura, Shinji; Minatoguchi, Shinya

2017-01-01

The aim of this study was to determine the effect of combination therapy consisting of acupuncture and traditional herbal medicine (Kampo medicine) for reducing the incidence rate of delirium in patients with cardiovascular (CV) disease in ICUs. Twenty-nine patients who had been urgently admitted to the ICU in the control period were treated with conventional intensive care. Thirty patients in the treatment period received conventional therapy plus a combination therapy consisting of acupuncture and herbal medicine. Acupuncture treatment was performed once a day, and the herbal formula was administered orally three times a day during the first week of the ICU stay. The standard acupuncture points were GV20, Ex-HN3, HT7, LI4, Liv3, and KI3, and the main herbal preparation was Kamikihito. The incident rates of delirium, assessed using the confusion assessment method for ICU, in the treatment and control period were compared. The incidence rate of delirium was significantly lower in the treatment group than in the control group (6.6% vs. 37.9%, [Formula: see text]). Moreover, sedative drugs and non-pharmacological approaches against aggressive behavior of patients who were delirious were used less in the treatment group than in the control group. No serious adverse events were observed in the treatment group. Combination therapy consisting of acupuncture and herbal medicine was found to be effective in lowering the incidence of delirium in patients with CV disease in ICUs. Further studies with a large sample size and parallel randomized controlled design would be required to establish the effects of this therapy.

The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

PubMed Central

2011-01-01

Background Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy. Trial registration Trial registration number NTR2774. PMID:21989041

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.

PubMed

Deiana, Serena; Harrington, Charles R; Wischik, Claude M; Riedel, Gernot

2009-01-01

The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.

Study design and rationale of "Synergistic Effect of Combination Therapy with Cilostazol and ProbUcol on Plaque Stabilization and Lesion REgression (SECURE)" study: a double-blind randomised controlled multicenter clinical trial

PubMed Central

2011-01-01

Background Probucol, a cholesterol-lowering agent that paradoxically also lowers high-density lipoprotein cholesterol has been shown to prevent progression of atherosclerosis. The antiplatelet agent cilostazol, which has diverse antiatherogenic properties, has also been shown to reduce restenosis in previous clinical trials. Recent experimental studies have suggested potential synergy between probucol and cilostazol in preventing atherosclerosis, possibly by suppressing inflammatory reactions and promoting cholesterol efflux. Methods/design The Synergistic Effect of combination therapy with Cilostazol and probUcol on plaque stabilization and lesion REgression (SECURE) study is designed as a double-blind, randomised, controlled, multicenter clinical trial to investigate the effect of cilostazol and probucol combination therapy on plaque volume and composition in comparison with cilostazol monotherapy using intravascular ultrasound and Virtual Histology. The primary end point is the change in the plaque volume of index intermediate lesions between baseline and 9-month follow-up. Secondary endpoints include change in plaque composition, neointimal growth after implantation of stents at percutaneous coronary intervention target lesions, and serum levels of lipid components and biomarkers related to atherosclerosis and inflammation. A total of 118 patients will be included in the study. Discussion The SECURE study will deliver important information on the effects of combination therapy on lipid composition and biomarkers related to atherosclerosis, thereby providing insight into the mechanisms underlying the prevention of atherosclerosis progression by cilostazol and probucol. Trial registration number ClinicalTrials (NCT): NCT01031667 PMID:21226953

Losartan/Hydrochlorothiazide: a review of its use in the treatment of hypertension and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy.

PubMed

Keating, Gillian M

2009-06-18

Losartan/hydrochlorothiazide (HCTZ) [Hyzaar(R)] is a fixed-dose combination of the angiotensin II receptor antagonist (angiotensin receptor blocker [ARB]) losartan and the thiazide diuretic HCTZ. It is indicated for the treatment of hypertension (including as initial therapy in severe hypertension) and for stroke risk reduction in patients with hypertension and left ventricular hypertrophy (LVH). Losartan/HCTZ is an effective combination therapy, lowering blood pressure (BP) to a greater extent than losartan or HCTZ alone in patients with hypertension. Other ARB/HCTZ fixed-dose combinations generally lowered BP to a greater extent than losartan/HCTZ in patients with hypertension, although whether this translates into improvements in cardiovascular outcomes is not known. In the LIFE study, losartan-based therapy was associated with a lower incidence of cardiovascular morbidity and mortality than atenolol-based therapy, mainly as a result of a reduced risk of stroke; the incidence of new-onset diabetes mellitus was also lower with losartan-based therapy. Losartan/HCTZ is a well tolerated combination therapy. Thus, losartan/HCTZ remains an important option in the treatment of hypertension, as well as being indicated to reduce stroke risk in patients with hypertension and LVH.

Interferon Alpha-2a Therapy in Patients with Refractory Behçet Uveitis.

PubMed

Hasanreisoglu, Murat; Cubuk, Mehmet Ozgur; Ozdek, Sengul; Gurelik, Gokhan; Aktas, Zeynep; Hasanreisoglu, Berati

2017-02-01

To report the results of IFNα2a therapy in patients with Behçet uveitis refractory to azathioprine-cyclosporine combination treatment. In a retrospective study, 39 patients treated with either azathioprine-cyclosporine combination treatment (group 1, n = 23) or IFNα2a (group 2, n = 16) with a diagnosis of ocular Behçet disease (BD), were included in the study. Group 2 consisted of patients who did not respond to conventional combination therapy, and were therefore treated with IFNα2a. Clinical response and relapse rates were recorded for each group. The mean number of uveitis attacks/year per patient was 0.8 ± 1.6 in Group 1. In Group 2, a significant decrease in the mean number of uveitis attacks/year per patient was observed after initiation of IFNα2a (2.4 ± 1.8 vs 1.3 ± 2.0) (p<0.05). When the two groups were compared after administration of IFNα2a therapy, no statistical difference was found in terms of uveitis attack/year and attack-free intervals, with a partial response to both treatments. IFNα2a therapy is an effective alternative for Behçet uveitis patients where conventional combination therapy fails.

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

PubMed

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

2016-12-01

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

Safety and tolerability of the switch from buprenorphine to buprenorphine/naloxone in an Italian addiction treatment centre.

PubMed

Stimolo, Clementina; Favero, Valentina Del; Zecchinato, Giancarlo; Buson, Roberto; Cusin, Davide; Pellachin, Patrizia; Simonetto, Pamela

2010-01-01

Abuse and misuse of pharmacological therapies represent major challenges in the healthcare system, particularly in patients receiving long-acting opioid drugs for the treatment of heroin or opioid addiction. The partial mu-opioid receptor agonist buprenorphine is used to treat opioid dependence, but diversion and misuse may occur. The sublingual combination formulation of buprenorphine and the opioid receptor antagonist naloxone (buprenorphine/naxolone) is associated with a reduced abuse potential, and has been shown to have promising efficacy for the treatment of opioid dependence. This observational study assessed the safety and efficacy of sublingual buprenorphine/naloxone combination therapy in patients with opioid dependence after therapeutic switch from buprenorphine monotherapy. A total of 94 patients being treated with buprenorphine monotherapy (average dose 8 mg/day; mean duration of therapy 840 days) were switched to buprenorphine/naloxone combination therapy. Patients were asked to rate their level of satisfaction with buprenorphine/naloxone combination treatment with respect to the management of withdrawal symptoms, and urinary toxicology tests were carried out before and 14 days after switching to combination therapy. Within 3 months, 75/94 patients (80%) previously treated with buprenorphine monotherapy had switched to sublingual buprenorphine/naloxone combination treatment (average dose buprenorphine 8 mg). Among patients receiving combination treatment for >3 months, 83% were receiving medication either weekly or fortnightly, based on the results of toxicological testing. A reduction in positive urinary toxicology tests was observed in patients within two weeks after being switched to combination treatment (before switch: 28, 9 and 2 positive tests for heroin, cocaine and heroin + cocaine, respectively vs 11, 3 and 1 after switch) and a total of 64 patients of the 75 who switched to combination therapy (85%) were satisfied with the management of withdrawal symptoms during buprenorphine/naloxone treatment. Few adverse events were reported and no patients dropped out of treatment. This study shows that switching from buprenorphine monotherapy to sublingual buprenorphine/naloxone combination therapy is effective and well tolerated, and associated with good control of withdrawal symptoms in the majority of patients. In addition, combination therapy reduced illicit drug use (based on negative urinary toxicology texts) and allowed the time between clinic visits to be increased.

Intravenous Milrinone in Treatment of Advanced Congestive Heart Failure

PubMed Central

Zewail, Aly M.; Nawar, Mohammad; Vrtovec, Bojan; Eastwood, Cathy; Kar, Biswajit; Delgado, Reynolds M.

2003-01-01

Phosphodiesterase inhibitors such as milrinone can relieve symptoms and improve hemodynamics in patients with advanced congestive heart failure. We retrospectively evaluated the hemodynamic and clinical outcomes of long-term combination therapy with intravenous milrinone and oral β-blockers in 65 patients with severe congestive heart failure (New York Heart Association class IV function and ejection fraction <25%) refractory to oral medical therapy. Fifty-one patients successfully began β-blocker therapy while on intravenous milrinone. Oral medical therapy was maximized when possible. The mean duration of milrinone treatment in this combination-treatment group was 269 days (range, 14–1,026 days). Functional class improved from IV to II–III with milrinone therapy. Twenty-four such patients tolerated β-blocker up-titration and were successfully weaned from milrinone. Sixteen patients (31%) died while receiving combination therapy; one died of sudden cardiac death (on treatment day 116); the other 15 died of progressive heart failure or other complications. Hospital admissions during the previous 6 months and admissions within 6 months after milrinone initiation stayed the same. Meanwhile, the total number of hospital days decreased from 450 to 380 (a 15.6% reduction), and the mean length of stay decreased by 1.4 days (a 14.7% reduction). We conclude that 1) milrinone plus β-blocker combination therapy is an effective treatment for heart failure even with β-blocker up-titration, 2) weaning from milrinone may be possible once medications are maximized, 3) patients' functional status improves on the combination regimen, and 4) treatment-related sudden death is relatively infrequent during the combination regimen. (Tex Heart Inst J 2003;30:109–13) PMID:12809251

Drug combination may be highly effective in recurrent ovarian cancer

Cancer.gov

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

Combination treatment of oral terbinafine with topical terbinafine and 10% urea ointment in hyperkeratotic type tinea pedis.

PubMed

Shi, Tian-Wei; Zhang, Jiang-An; Zhang, Xian-Wei; Yu, Hong-Xing; Tang, Yong-Bo; Yu, Jian-Bin

2014-09-01

Hyperkeratotic-type tinea pedis is chronic and recalcitrant to topical antifungal agents. Some topical antifungal agents are effective; however, long duration of therapy is required, which often reduce the treatment compliance of patients. To seek for short period therapy of hyperkeratotic type tinea pedis, in this study, we observed the efficacy and safety of treatment of topical terbinafine and 10% urea ointment combined oral terbinafine. Participants with hyperkeratotic type tinea pedis were randomly assigned to two groups. Patients in group I were treated with oral terbinafine for 2 weeks and topical terbinafine and 10% urea ointment for 4 weeks, whereas in group II, only the above topical agents were applied for 12 weeks. Clinical improvement rates and fungal eradication rates were compared between the two groups at 24 weeks after the initiation of treatment. The group I had stopped the topical therapy 8 weeks earlier than group II. There were no significant differences in mycological eradication rates and clinical improvement rates between the two groups, besides, no major side effects were noted in both groups. The short combination therapy with oral terbinafine was effective and safe; it should be a valuable option for patients with hyperkeratotic type tinea pedis. © 2014 Blackwell Verlag GmbH.

Effectiveness of postoperative physical therapy for upper-limb impairments after breast cancer treatment: a systematic review.

PubMed

De Groef, An; Van Kampen, Marijke; Dieltjens, Evi; Christiaens, Marie-Rose; Neven, Patrick; Geraerts, Inge; Devoogdt, Nele

2015-06-01

To systematically review the effectiveness of various postoperative physical therapy modalities and timing of physical therapy after treatment of breast cancer on pain and impaired range of motion (ROM) of the upper limb. We searched the following databases: PubMed/MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, Physiotherapy Evidence Database, and Cochrane. Articles published until October 2012 were included. Only (pseudo) randomized controlled trials and nonrandomized experimental trials investigating the effectiveness of passive mobilization, manual stretching, myofascial therapy, and/or exercise therapy and timing of physical therapy after treatment for breast cancer are reviewed. Primary outcomes are pain of the upper limb and/or ROM of the shoulder. Secondary outcomes are decreased shoulder strength, arm lymphedema, limitations in activities of daily living, decreased quality of life, and wound drainage volume. Physical therapy modalities had to be started in the first 6 weeks after surgery. Articles were selected by 2 independent researchers in 3 phases and compared for consensus. First the titles were analyzed, and then the selected abstracts and finally the full texts were reviewed. Eighteen randomized controlled trials were included in the review. Three studies investigated the effect of multifactorial therapy: 2 studies confirmed that the combination of general exercises and stretching is effective for the treatment of impaired ROM another study showed that passive mobilization combined with massage had no beneficial effects on pain and impaired ROM. Fifteen studies investigated the effectiveness of a single physical therapy modality. One study of poor quality found evidence supporting the beneficial effects of passive mobilization. The only study investigating the effect of stretching did not find any beneficial effects. No studies were found about the effectiveness of myofascial therapy in the postoperative phase. Five studies found that active exercises were more effective than no therapy or information on the treatment of impairments of the upper limb. Three studies supported the early start of exercises for recovery of shoulder ROM, whereas 4 studies supported the delay of exercises to avoid prolonged wound healing. Multifactorial physical therapy (ie, stretching, exercises) and active exercises were effective to treat postoperative pain and impaired ROM after treatment for breast cancer. High-quality studies are necessary to determine the effectiveness of passive mobilization, stretching, and myofascial therapy as part of the multifactorial treatment. In addition, the appropriate timing and content of the exercise programs need to be further investigated. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: significance of combination therapy.

PubMed

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

2014-11-12

Bromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored. The growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay. Bromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy. We report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from cell cycle arrest, apoptosis and autophagy. Towards the development of novel strategies for the enhancement of microscopic cytoreduction, our results lay the basis for further evaluation of this formulation in locoregional approaches to peritoneal surface malignancies and carcinomatosis.

Fixed-dose combination therapy for the prevention of cardiovascular disease

PubMed Central

de Cates, Angharad N; Farr, Matthew RB; Wright, Nicola; Jarvis, Morag C; Rees, Karen; Ebrahim, Shah; Huffman, Mark D

2014-01-01

Background Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, yet CVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure and cholesterol lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of CVD by up to 80% given its potential for better adherence and lower costs. Objectives To determine the effectiveness of fixed-dose combination therapy on reducing fatal and non-fatal CVD events and on improving blood pressure and lipid CVD risk factors for both primary and secondary prevention of CVD. We also aimed to determine discontinuation rates, adverse events, health-related quality of life, and costs of fixed-dose combination therapy. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library(2013, Issue 6), MEDLINE Ovid (1946 to week 2 July 2013), EMBASE Ovid (1980 to Week 28 2013), ISI Web of Science (1970 to 19 July 2013), and the Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment Database (HTA), and Health Economics Evaluations Database (HEED) (2011, Issue 4) in The Cochrane Library. We used no language restrictions. Selection criteria We included randomised controlled trials of a fixed-dose combination therapy including at least one blood pressure lowering and one lipid lowering component versus usual care, placebo, or a single drug active component for any treatment duration in adults ≥ 18 years old with no restrictions on presence or absence of pre-existing cardiovascular disease. Data collection and analysis Three review authors independently selected studies for inclusion and extracted the data. We evaluated risk of bias using the Cochrane risk of bias assessment tool. We sought to include outcome data on all-cause mortality, fatal and non-fatal CVD events, adverse events, changes in systolic and diastolic blood pressure, total and low density lipoprotein (LDL) cholesterol concentrations, discontinuation rates, quality of life, and costs. We calculated risk ratios (RR) for dichotomous data and weighted mean differences (MD) for continuous data with 95% confidence intervals (CI) using fixed-effect models when heterogeneity was low (I2 < 50%) and random-effects models when heterogeneity was high (I2 > 50%). Main results We found nine randomised controlled trials with a total of 7047 participants. Seven of the nine trials evaluated the effects of fixed-dose combination therapy on primary CVD prevention, and the trial length ranged from six weeks to 15 months. We found a moderate to high risk of bias in the domains of selection, performance, detection, attrition, and other types of bias in five of the nine trials. Compared with the comparator groups, the effects of the fixed-dose combination treatment on mortality (1.2% versus 1.0%, RR 1.26, 95% CI 0.67 to 2.38, N = 3465) and cardiovascular events (4.0% versus 2.9%, RR 1.38, 95% CI 0.91 to 2.10, N = 2479) were uncertain (low quality evidence). The low event rates for these outcomes, limited availability of data as only two out of nine trials reported on these outcomes, and a high risk of bias in at least one domain suggest that these results should not be viewed with confidence. Adverse events were common in both the intervention (30%) and comparator (24%) groups, with participants randomised to fixed-dose combination therapy being 20% (95% CI 9% to 30%) more likely to report an adverse event. Notably, no serious adverse events were reported. Compared with placebo, the rate of discontinuation among participants randomised to fixed-dose combination was higher (14% versus 11%, RR 1.26 95% CI 1.02 to 1.55). The weighted mean differences in systolic and diastolic blood pressure between the intervention and control arms were -7.05 mmHg (95% CI -10.18 to -3.87) and -3.65 mmHg (95% CI -5.44 to -1.85), respectively. The weighted mean differences (95% CI) in total and LDL cholesterol between the intervention and control arms were -0.75 mmol/L (95% CI -1.05 to -0.46) and -0.81 mmol/L (95% CI -1.09 to -0.53), respectively. There was a high degree of statistical heterogeneity in comparisons of blood pressure and lipids (I2 ≥ 70% for all) that could not be explained, so these results should be viewed with caution. Fixed-dose combination therapy improved adherence to a multi-drug strategy by 33% (26% to 41%) compared with usual care, but this comparison was reported in only one study. The effects of fixed-dose combination therapy on quality of life are uncertain, though these results were reported in only one trial. No trials reported costs. Authors' conclusions Compared with placebo, single drug active component, or usual care, the effects of fixed-dose combination therapy on all-cause mortality or CVD events are uncertain; only few trials report these outcomes and the included trials were primarily designed to observe changes in CVD risk factor levels rather than clinical events. Reductions in blood pressure and lipid parameters are generally lower than those previously projected, though substantial heterogeneity of results exists. Fixed-dose combination therapy is associated with modest increases in adverse events compared with placebo, single drug active component, or usual care but may be associated with improved adherence to a multidrug regimen. Ongoing trials of fixed-dose combination therapy will likely inform key outcomes. PMID:24737108

[Individual parameters of general low-frequency magnetic therapy as a possibility for improving the clinical efficacy of the combined treatment of patients with essential arterial hypertension].

PubMed

Fedotov, V D; Maslov, A G; Lobkaeva, E P; Krylov, V N; Obukhova, E O

2012-01-01

A new approach is proposed for the choice of low-frequency magnetic therapy on an individual basis using the results of analysis of heart rhythm variability. The clinical efficiency of low-frequency magnetic therapy incorporated in the combined treatment of 65 patients aged between 25 and 45 years with essential arterial hypertension was estimated. The statistically significant positive effects of the treatment included normalization of blood pressure and characteristics of heart rhythm variability as well as resolution of clinical symptoms of vegetative dysregulation.

[New direct-acting antiviral agents for the treatment of chronic hepatitis C in 2014].

PubMed

Cornberg, M; Höner zu Siederdissen, C; Maasoumy, B; Manns, M P

2014-04-01

The development of direct-acting antiviral agents (DAA) against the hepatitis C virus (HCV) has seen enormous progress in recent years. In 2011, the first protease inhibitors boceprevir (BOC) and telaprevir (TLV) were approved, which still need to be combined with pegylated interferon α (PEG-IFN α) and ribavirin (RBV) and are used only in patients with genotype 1. With sofosbuvir (SOF) and simeprevir (SMV), two new DAA are available. More DAA are in clinical development. Which changes in the treatment of chronic hepatitis C infection can be expected with the approval of the new DAA in 2014? Relevant phase IIb and phase III studies for the approval in 2014 were considered for drugs approved by the FDA or EMA at the editorial deadline. For patients with genotype 1, the combination of SOF, SMV or faldaprevir with PEG-IFN α and RBV was successfully evaluated in phase III studies. In contrast to previous treatment with PEG-IFN α, RBV and telaprevir (TLV) or boceprevir (BOC), therapy can be shortened in most cases with a significantly improved side-effect profile. Cure rates above 80 % are possible. Data are also available for an interferon-free therapy with either SOF and RBV or SOF and SMV in GT-1 patients. SVR rates exceeding 60 % and up to 90 % are possible. However, treatment experience with these combinations is low and an unrestricted interferon-free therapy for genotype 1 should not be expected before 2015. For patients with genotypes 2 and 3, valid data for interferon-free therapies are available. The combination of SOF and RBV for 12 weeks in genotype 2 and 24 weeks for genotype 3 is effective and shows equal or superior cure rates with fewer side effects than the PEG-IFN α/RBV therapy. For patients with genotype 1, the duration of therapy can be further reduced with better side effect profile. In certain situations, therapy without PEG-IFN α is possible and should be considered. For patients with genotypes 2 and 3, an interferon-free therapy will be standard of care in 2014.

Efficacy of rasagiline for the treatment of Parkinson's disease: an updated meta-analysis.

PubMed

Chang, Ying; Wang, Li-Bo; Li, Dan; Lei, Ke; Liu, Song-Yan

2017-08-01

Rasagiline is a second-generation potent selective inhibitor of monoamine oxidase-B. The aim of the study was to analyze the effectiveness of rasagiline in treatment of Parkinson's disease (PD), both as monotherapy and combination therapy. Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 9 March 2016 using the keywords: Rasagiline, Azilect, Parkinson's disease. Randomized controlled trials of patients with PD who were randomized to treatment with rasagiline or placebo were included. Outcomes were unified Parkinson's disease rating scale (UPDRS) and the three subscales. Ten studies fulfilled the inclusion criteria and 2709 patients were evaluated. The overall analysis revealed a significant improvement in change of total UPDRS scores in 1 mg/day and 2 mg/day rasagiline groups compared to placebo. Significant improvement in Part I (Mentation) of UPDRS scores was observed in 1 mg/day, but not in 2 mg/day rasagiline treatment group. Part II (ADL) and Part III (Motor) subscales significantly improved with both doses of rasagiline. Both monotherapy and combination therapy significantly improved total UPDRS scores. Our results confirm the efficacy of rasagiline in PD. Further studies are required to establish the optimal dose of rasagiline, as well as to determine its effectiveness in different combination therapy protocols. KEY MESSAGES Rasagiline treatment was associated with significant improvement of UPDRS scores and the scores of the subscales. Both monotherapy and combination therapy significantly improved total UPDRS scores. Effect of rasagiline on total UPDRS scores was not dose-dependent.

Garlic induces a shift in cytokine pattern in Leishmania major-infected BALB/c mice.

PubMed

Ghazanfari, T; Hassan, Z M; Ebtekar, M; Ahmadiani, A; Naderi, G; Azar, A

2000-11-01

The regulation of T helper (Th)1- and Th2-type cytokine patterns is important in the final outcome of leishmaniasis in human and murine models. We examined the efficacy of garlic therapy or a combination of garlic and an antimonial drug (glucantime) in promoting healing and regulation of Th1/Th2 cytokine patterns in highly susceptible BALB/c mice infected with Leishmania major. Separate groups of infected mice received 20 mg/kg/day garlic, 60 mg/kg/day glucantime or a combination of the two, from day 30 after infection for 2 weeks. An enzyme-linked immunosorbant assay (ELISA) was performed on spleen cell culture supernatants for interferon(IFN)-gamma interleukin(IL)-2, IL-4 and IL-10. The results indicate that garlic therapy is more effective than the usual antileishmanial drug in curing the infection. Garlic-treated mice developed Th1-type cytokine responses. In contrast, glucantime therapy led to a Th2-type response in the control group with a lower level of IL-2. However, a combination of garlic and glucantime treatment was more effective than either treatment alone, and resulted in a Th1-type response similar to that which developed with garlic treatment. These results suggest that garlic extract in combination with an antimonial drug, may provide effective therapy against L. major. The immunomodulatory properties of garlic were elucidated in terms of shifting the cytokine response to a Th1-type pattern and therefore causing the protective response.

Combined Therapy of Iron Chelator and Antioxidant Completely Restores Brain Dysfunction Induced by Iron Toxicity

PubMed Central

Sripetchwandee, Jirapas; Pipatpiboon, Noppamas; Chattipakorn, Nipon; Chattipakorn, Siriporn

2014-01-01

Background Excessive iron accumulation leads to iron toxicity in the brain; however the underlying mechanism is unclear. We investigated the effects of iron overload induced by high iron-diet consumption on brain mitochondrial function, brain synaptic plasticity and learning and memory. Iron chelator (deferiprone) and antioxidant (n-acetyl cysteine) effects on iron-overload brains were also studied. Methodology Male Wistar rats were fed either normal diet or high iron-diet consumption for 12 weeks, after which rats in each diet group were treated with vehicle or deferiprone (50 mg/kg) or n-acetyl cysteine (100 mg/kg) or both for another 4 weeks. High iron-diet consumption caused brain iron accumulation, brain mitochondrial dysfunction, impaired brain synaptic plasticity and cognition, blood-brain-barrier breakdown, and brain apoptosis. Although both iron chelator and antioxidant attenuated these deleterious effects, combined therapy provided more robust results. Conclusion In conclusion, this is the first study demonstrating that combined iron chelator and anti-oxidant therapy completely restored brain function impaired by iron overload. PMID:24400127

Radiobiological Optimization of Combination Radiopharmaceutical Therapy Applied to Myeloablative Treatment of Non-Hodgkin’s Lymphoma

PubMed Central

Hobbs, Robert F; Wahl, Richard L; Frey, Eric C; Kasamon, Yvette; Song, Hong; Huang, Peng; Jones, Richard J; Sgouros, George

2014-01-01

Combination treatment is a hallmark of cancer therapy. Although the rationale for combination radiopharmaceutical therapy was described in the mid ‘90s, such treatment strategies have only been implemented clinically recently, and without a rigorous methodology for treatment optimization. Radiobiological and quantitative imaging-based dosimetry tools are now available that enable rational implementation of combined targeted radiopharmaceutical therapy. Optimal implementation should simultaneously account for radiobiological normal organ tolerance while optimizing the ratio of two different radiopharmaceuticals required to maximize tumor control. We have developed such a methodology and applied it to hypothetical myeloablative treatment of non-hodgkin’s lymphoma (NHL) patients using 131I-tositumomab and 90Y-ibritumomab tiuxetan. Methods The range of potential administered activities (AA) is limited by the normal organ maximum tolerated biologic effective doses (MTBEDs) arising from the combined radiopharmaceuticals. Dose limiting normal organs are expected to be the lungs for 131I-tositumomab and the liver for 90Y-ibritumomab tiuxetan in myeloablative NHL treatment regimens. By plotting the limiting normal organ constraints as a function of the AAs and calculating tumor biological effective dose (BED) along the normal organ MTBED limits, the optimal combination of activities is obtained. The model was tested using previously acquired patient normal organ and tumor kinetic data and MTBED values taken from the literature. Results The average AA values based solely on normal organ constraints was (19.0 ± 8.2) GBq with a range of 3.9 – 36.9 GBq for 131I-tositumomab, and (2.77 ± 1.64) GBq with a range of 0.42 – 7.54 GBq for 90Y-ibritumomab tiuxetan. Tumor BED optimization results were calculated and plotted as a function of AA for 5 different cases, established using patient normal organ kinetics for the two radiopharmaceuticals. Results included AA ranges which would deliver 95 % of the maximum tumor BED, which allows for informed inclusion of clinical considerations, such as a maximum allowable 131I administration. Conclusions A rational approach for combination radiopharmaceutical treatment has been developed within the framework of a proven 3-dimensional personalized dosimetry software, 3D-RD, and applied to the myeloablative treatment of NHL. We anticipate combined radioisotope therapy will ultimately supplant single radioisotope therapy, much as combination chemotherapy has substantially replaced single agent chemotherapy. PMID:23918734

Successful Treatment of Fluconazole-Resistant Oropharyngeal Candidiasis by a Combination of Fluconazole and Terbinafine

PubMed Central

Ghannoum, Mahmoud A.; Elewski, Boni

1999-01-01

Increasing incidence of resistance to conventional antifungal therapy has demanded that novel therapies be introduced. Recent in vitro studies have shown that combinations involving azoles and allylamines may be effective in inhibiting fluconazole-resistant fungi. In this report, we describe the case of a 39-year-old woman who presented with white patches on her buccal mucosa, tongue, and palate with a bright erythematous erosive base. A fungal culture revealed Candida albicans. The patient failed to respond to the initially prescribed fluconazole therapy. Failure of therapy can be attributed to a developed resistance to fluconazole from the patient’s intermittent use of this antifungal agent at varying dosages for the preceding 2 years due to a diagnosis of onychomycosis. In vitro testing of the culture from the patient showed elevated MICs of fluconazole, itraconzole, and terbinafine (MICs were 32, 0.5, and 64 μg/ml, respectively). Our goal was to combine therapies of fluconazole and terbinafine in an attempt to clear the fungal infection. Impressively, this combination resulted in the clearing of the clinical symptoms and the patient has successfully been asymptomatic for more than 12 months posttreatment. PMID:10548586

Acupuncture and related therapies used as add-on or alternative to prokinetics for functional dyspepsia: overview of systematic reviews and network meta-analysis.

PubMed

Ho, Robin S T; Chung, Vincent C H; Wong, Charlene H L; Wu, Justin C Y; Wong, Samuel Y S; Wu, Irene X Y

2017-09-04

Prokinetics for functional dyspepsia (FD) have relatively higher number needed to treat values. Acupuncture and related therapies could be used as add-on or alternative. An overview of systematic reviews (SRs) and network meta-analyses (NMA) were performed to evaluate the comparative effectiveness of different acupuncture and related therapies. We conducted a comprehensive literature search for SRs of randomized controlled trials (RCTs) in eight international and Chinese databases. Data from eligible RCTs were extracted for random effect pairwise meta-analyses. NMA was used to explore the most effective treatment among acupuncture and related therapies used alone or as add-on to prokinetics, compared to prokinetics alone. From five SRs, 22 RCTs assessing various acupuncture and related therapies were included. No serious adverse events were reported. Two pairwise meta-analyses showed manual acupuncture has marginally stronger effect in alleviating global FD symptoms, compared to domperidone or itopride. Results from NMA showed combination of manual acupuncture and clebopride has the highest probability in alleviating patient reported global FD symptom. Combination of manual acupuncture and clebopride has the highest probability of being the most effective treatment for FD symptoms. Patients who are contraindicated for prokinetics may use manual acupuncture or moxibustion as alternative. Future confirmatory comparative effectiveness trials should compare clebopride add-on manual acupuncture with domperidone add-on manual acupuncture and moxibustion.

[Effects of combined natural hirudin and hyperbaric oxygen therapy on survival of transplanted random-pattern skin flap in rats].

PubMed

Cai, Jieyun; Lin, Bojie; Pan, Xinyuan; Cui, Jia; Pradhan, Rohan; Yin, Guoqian

2018-04-01

To investigate the effect of natural hirudin combined with hyperbaric oxygen therapy on the survival of transplanted random-pattern skin flap in rats. A random-pattern skin flap in size of 10.0 cm×2.5 cm was elevated on the dorsum of 72 Sprague Dawley rats. Then the 72 rats were randomly divided into 4 groups ( n =18) according to the therapy method. At immediate and within 4 days after operation, the rats were treated with normal saline injection in control group, normal saline injection combined with hyperbaric oxygen treatment in hyperbaric oxygen group, the natural hirudin injection in natural hirudin group, and the natural hirudin injection combined with hyperbaric oxygen treatment in combined group. The flap survival was observed after operation, and survival rate was evaluated at 6 days after operation. The skin samples were collected for histological analysis, microvessel density (MVD) measurement, and evaluation of tumor necrosis factor α (TNF-α) expression level by the immunohistochemical staining at 2 and 4 days after operation. Partial necrosis occurred in each group after operation, and the flap in combined group had the best survival. The survival rate of flap was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, and in combined group than in hyperbaric oxygen group and natural hirudin group ( P <0.05). There was no significant difference between hyperbaric oxygen group and natural hirudin group ( P >0.05). At 2 days, more microvascular structure was observed in hyperbaric oxygen group, natural hirudin group, and combined group in comparison with control group; while plenty of inflammatory cells infiltration in all groups. At 4 days, the hyperbaric oxygen group, natural hirudin group, and the combined group still showed more angiogenesis. Meanwhile, there was still infiltration of inflammatory cells in control group, inflammatory cells in the other groups were significantly reduced when compared with at 2 days. At 2 days, the MVD was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group ( P <0.05); the expression of TNF-α was significantly lower in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group ( P <0.05). There was no significant difference in above indexes between hyperbaric oxygen group, natural hirudin group, and combined group ( P >0.05). At 4 days, the MVD was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, in natural hirudin group and combined group than in hyperbaric oxygen group ( P <0.05). The expression of TNF-α was significantly lower in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, in combined group than in natural hirudin group and hyperbaric oxygen group ( P <0.05). Hyperbaric oxygen and natural hirudin therapy after random-pattern skin flap transplantation can improve the survival of flaps. Moreover, combined therapy is seen to exhibit significant synergistic effect. This effect maybe related to promotion of angiogenesis and the reduction of inflammation response.

Combination of magnetic resonance imaging and diffuse optical spectroscopy to predict radiation response in the breast: an exploratory pilot study

NASA Astrophysics Data System (ADS)

Klifa, C.; Hattangadi, J.; Watkins, M.; Li, A.; Sakata, T.; Tromberg, B.; Hylton, N.; Park, C.

2007-02-01

Radiation therapy (RT) is a standard treatment after lumpectomy for breast cancer, involving a typical course of approximately 6-7 weeks of daily treatment. Many women find this cumbersome and costly, and therefore many are left with the option of mastectomy. Many groups are now investigating novel ways to deliver RT, by using different techniques and shortening the course of treatment. However, the efficacy and side effects of these strategies are not known. In this project, we wish to develop noninvasive imaging tools that would allow us to measure radiation dose effects in women with breast cancer. We hope this will lead to new ways to identify individuals who may not need radiation therapy, who may safely be treated with new accelerated techniques, or who should be treated with the standard radiation therapy approach. We propose to study the effect of radiation therapy using a combination of two imaging modalities: 1) magnetic resonance imaging (MRI) which will provide detailed information on breast structures and blood vessels and 2) near infra-red diffuse optical spectroscopy (DOS), which measures local biologic properties of breast tissue. Our hypothesis is that by using a combination of modalities we will be able to better characterize radiation effects in breast tissue, by measuring differences between the radiated and non-irradiated breast. The development of novel non-invasive tools providing information about how individuals respond to radiation therapy can lead to important improvement of radiation treatment, and ultimately help guide individualized treatment programs in the future.

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

PubMed

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

2017-03-01

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

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

PubMed Central

Moeinian, Mahsa; Ghasemi-Niri, Seyedeh Farnaz; Mozaffari, Shilan; Abdolghaffari, Amir Hossein; Baeeri, Maryam; Navaea-Nigjeh, Mona; Abdollahi, Mohammad

2014-01-01

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model. METHODS: Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon. RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO. CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting. PMID:25152589

Combination therapy with andrographolide and D-penicillamine enhanced therapeutic advantage over monotherapy with D-penicillamine in attenuating fibrogenic response and cell death in the periportal zone of liver in rats during copper toxicosis

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

Roy, Dijendra Nath; Sen, Gargi; Chowdhury, Kaustav Dutta

2011-01-01

Long treatment regime with D-penicillamine is needed before it can exert clinically meaningful benefits in the treatment of copper toxicosis. The consequence of long-term D-penicillamine treatment is associated with numerous side effects. The limitations of D-penicillamine monotherapy prompted us to search for more effective treatment strategies that could decrease the duration of D-penicillamine therapy. The present study was designed to evaluate the therapeutic potential of D-penicillamine in combination with another hepatoprotective drug, andrographolide in treatment of copper toxicosis in rats. D-penicillamine treatment led to the excretion of copper through urine. Addition of andrographolide to D-penicillamine regime appeared to increase protectionmore » of liver by increasing the biliary excretion of copper and reduction in cholestatic injury. The early removal of the causative agent copper during combination treatment was the most effective therapeutic intervention that contributed to the early rectification of fibrosis in liver. Combination treatment reduced Kupffer cells accumulation and TNF{alpha} production in liver of copper exposed rats. In particular, andrographolide mediated the anti-inflammatory effect by inhibiting the cytokine production. However, another possible mechanism of cytoprotection of andrographolide was decreasing mitochondrial production of superoxide anions that resulted in better restoration of mitochondrial dysfunction during combination therapy than monotherapy. Furthermore, ROS inhibition by combination regimen resulted in significant decline in activation of caspase cascade. Inhibition of caspases attenuated apoptosis of hepatocytes, induced by chronic copper exposure. In summary, this study suggested that added benefit of combination treatment over use of either agent alone in alleviating the hepatotoxicity and fibrosis associated with copper toxicosis.« less

Validity, Significance, Strengths, Limitations, and Evidentiary Value of Real-World Clinical Data for Combination Therapy in Alzheimer's Disease: Comparison of Efficacy and Effectiveness Studies

PubMed Central

Atri, Alireza; Rountree, Susan D.; Lopez, Oscar L.; Doody, Rachelle S.

2012-01-01

Background Randomized controlled efficacy trials (RCTs), the scientific gold standard, are required for regulatory approval of Alzheimer's disease (AD) interventions, yet provide limited information regarding real-world therapeutic effectiveness. Objective: To compare the nature of evidence regarding the combination of approved AD treatments from RCTs versus long-term observational controlled studies (LTOCs). Methods Comparisons of strengths, limitations, and evidence level for monotherapy [cholinesterase inhibitor (ChEI) or memantine] and combination therapy (ChEI + memantine) in RCTs versus LTOCs. Results RCTs examined highly selected populations over months. LTOCs collected data across multiple AD stages in large populations over many years. RCTs and LTOCs show similar patterns favoring combination over monotherapy over placebo/no treatment. Long-term combination therapy compared to monotherapy reduced cognitive and functional decline and delayed time to nursing home admission. Persistent treatment was associated with slower decline. While LTOCs used control groups, adjusted for multiple covariates, had higher external validity, and favorable ethical, practical and cost considerations, their limitations included potential selection bias due to lack of placebo comparisons and randomization. Conclusions Naturalistic LTOCs provide complementary long-term level II evidence to complement level I evidence from short-term RCTs regarding therapeutic effectiveness in AD that may otherwise be unobtainable. A coordinated strategy/consortium to pool LTOC data from multiple centers to estimate long-term comparative effectiveness, risks/benefits, and costs of AD treatments is needed. PMID:22327239

Augmentation of the Differentiation Response to Antitumor Antimalarials

DTIC Science & Technology

2005-07-01

An impeding challenge to breast cancer drug therapies is the availability of more effective and less toxic chemotherapeutic agents that do not relay...enhanced antiproliferative, differentiation, and histone acetylation responses are achieved during combination therapy with ATRA rather than the...agents for cancer differentiation therapy . We showed that five antiproliferative quinolime compounds in the National Cancer Institute database

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

PubMed

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

2018-05-01

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

Maintenance of remission with combination etanercept-DMARD therapy versus DMARDs alone in active rheumatoid arthritis: results of an international treat-to-target study conducted in regions with limited biologic access.

PubMed

Pavelka, Karel; Akkoç, Nurullah; Al-Maini, Mustafa; Zerbini, Cristiano A F; Karateev, Dmitry E; Nasonov, Evgeny L; Rahman, Mahboob U; Pedersen, Ronald; Dinh, Andrew; Shen, Qi; Vasilescu, Radu; Kotak, Sameer; Mahgoub, Ehab; Vlahos, Bonnie

2017-09-01

In this transglobal, randomized, double-blind, placebo-controlled, treat-to-target study, the maintenance of efficacy was compared between biologic-and biologic-free-disease-modifying antirheumatic drug (DMARD) combination regimens after low disease activity (LDA) was achieved with biologic DMARD induction therapy. Patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy received open-label etanercept 50 mg subcutaneously once weekly plus methotrexate with or without other conventional synthetic (cs) DMARDs for 24 weeks. Patients achieving LDA [disease activity score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) <3.2] at week 24 were randomized to receive etanercept-methotrexate combination therapy or placebo-methotrexate combination therapy, with or without other csDMARDs, for 28 weeks. In the open-label period, 72% of patients achieved DAS28-ESR LDA at week 24. Patients enrolled in the double-blind period had long-standing rheumatoid arthritis and high disease activity at baseline (mean duration, 8.1 years; DAS28-ESR, 6.4). In the etanercept and placebo combination groups, 44% versus 17% achieved DAS28-ESR LDA and 34 versus 13% achieved DAS28-ESR remission at week 52 (p < 0.001). Adverse events were reported in 37 and 43%, serious adverse events in 0 and 4%, and serious infections in 0 and 2% in these groups, respectively, in the double-blind period. After induction of response with etanercept combination therapy following a treat-to-target approach in patients with long-standing rheumatoid arthritis and high disease activity at baseline, the etanercept combination regimen was significantly more effective in maintaining LDA and remission than a biologic-free regimen. ClinicalTrials.gov identifier. NCT01578850.

The effect of direct renin inhibition alone and in combination with ACE inhibition on endothelial function, arterial stiffness, and renal function in type 1 diabetes.

PubMed

Cherney, David Z I; Scholey, James W; Jiang, Shan; Har, Ronnie; Lai, Vesta; Sochett, Etienne B; Reich, Heather N

2012-11-01

Diabetes is associated with renin-angiotensin system (RAS) activation, leading to renal and systemic vascular dysfunction that contribute to end-organ injury and significant morbidity. RAS blockade with ACE inhibitors reduces, but does not abolish, RAS effects. Accordingly, our aim was to determine if direct renin inhibition alone, and in combination with an ACE inhibitor, corrects early hemodynamic abnormalities associated with type 1 diabetes. Arterial stiffness (augmentation index), flow-mediated vasodilatation (FMD), and renal hemodynamic function (inulin and paraaminohippurate clearance) were measured at baseline under clamped euglycemic and hyperglycemic conditions (n = 21). Measures were repeated after 4 weeks of aliskiren therapy and again after aliskiren plus ramipril. Blood pressure-lowering effects of aliskiren were similar during clamped euglycemia and hyperglycemia. Combination therapy augmented this effect under both glycemic conditions (P = 0.0005). Aliskiren reduced arterial stiffness under clamped euglycemic and hyperglycemic conditions, and the effects were augmented by dual RAS blockade (-3.4 ± 11.2 to -8.0 ± 11.5 to -14.3 ± 8.4%, respectively, during euglycemia, P = 0.0001). During clamped euglycemia, aliskiren increased FMD; dual therapy exaggerated this effect (5.1 ± 3.3 to 7.5 ± 3.0 to 10.8 ± 3.5%, repeated-measures ANOVA, P = 0.0001). Aliskiren monotherapy caused renal vasodilatation during clamped hyperglycemia only. In contrast, dual therapy augmented renal vasodilatory effects during clamped euglycemia and hyperglycemia. In patients with uncomplicated type 1 diabetes, aliskiren-based dual RAS blockade is associated with greater arterial compliance, FMD, and renal vasodilatation.

Manual Therapy With Cryotherapy Versus Manual Therapy With Kinesio Taping for Males With Lumbar Discopathy: A Pilot Randomized Trial.

PubMed

Lizis, Pawel; Kobza, Wojciech

2017-06-23

Context • Numerous modalities of therapeutic interventions exist for lumbar discopathy. Manual therapy is one option, although its effectiveness remains controversial. The addition of cryotherapy to manual therapy may enhance the health benefits in patients with lumbar discopathy.  Objective • The study intended to evaluate the efficacy of manual therapy combined with cryotherapy vs manual therapy combined with Kinesio taping for males with lumbar discopathy. Design • The research team designed a pilot randomized trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Setting • The study occurred in the Physiotherapy Outpatient Department of the Regional Hospital (Zywiec, Poland). Participants • The participants were 40 males with lumbar discopathy, aged 30-75 y, who were patients in the department at the hospital. Intervention • The participants were randomly assigned to an intervention group that received Kaltenborn-Evjenth orthopedic manual therapy (KEOMT) combined with cryotherapy, the KEOMT-C group (n = 20), or to a control group that received KEOMT combined with Kinesio taping, the KEOMT-K group (n = 20). The participants in both groups received 10 treatments, 2 per wk for 5 wk. Outcome Measures • The primary outcome was measured using a visual analog scale and the Laitinen scale pain ratings. The secondary outcome measured the quality of life using the short form-36 questionnaire. The participants completed the tests at baseline and postintervention. Results • After the treatments, the intervention group had significantly lower scores than the control group for pain as well as significantly higher scores for quality of life. Conclusions • Patients achieved better health benefits from manual therapy when it was combined with cryotherapy.

Efficacy and safety of fosfomycin plus imipenem as rescue therapy for complicated bacteremia and endocarditis due to methicillin-resistant Staphylococcus aureus: a multicenter clinical trial.

PubMed

del Río, Ana; Gasch, Oriol; Moreno, Asunción; Peña, Carmen; Cuquet, Jordi; Soy, Dolors; Mestres, Carlos A; Suárez, Cristina; Pare, Juan C; Tubau, Fe; Garcia de la Mària, Cristina; Marco, Francesc; Carratalà, Jordi; Gatell, José M; Gudiol, Francisco; Miró, José M

2014-10-15

There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia. The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy). The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse. Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Macrophage-directed immunotherapy as adjuvant to photodynamic therapy of cancer.

PubMed

Korbelik, M; Naraparaju, V R; Yamamoto, N

1997-01-01

The effect of Photofrin-based photodynamic therapy (PDT) and adjuvant treatment with serum vitamin D3-binding protein-derived macrophage-activating factor (DBPMAF) was examined using a mouse SCCVII tumour model (squamous cell carcinoma). The results show that DBPMAF can markedly enhance the curative effect of PDT. The most effective DBPMAF therapy consisted of a combination of intraperitoneal and peritumoral injections (50 and 0.5 ng kg-1 respectively) administered on days 0, 4, 8 and 12 after PDT. Used with a PDT treatment curative to 25% of the treated tumours, this DBPMAF regimen boosted the cures to 100%. The DBPMAF therapy alone showed no notable effect on the growth of SCCVII tumour. The PDT-induced immunosuppression, assessed by the evaluation of delayed-type contact hypersensitivity response in treated mice, was greatly reduced with the combined DBPMAF treatment. These observations suggest that the activation of macrophages in PDT-treated mice by adjuvant immunotherapy has a synergistic effect on tumour cures. As PDT not only reduces tumour burden but also induces inflammation, it is proposed that recruitment of the activated macrophages to the inflamed tumour lesions is the major factor for the complete eradication of tumours.