Safety of Tamsulosin: A Systematic Review of Randomized Trials with a Focus on Women and Children.

PubMed

Kaplan, Steven A; Chughtai, Bilal I

2018-05-08

Although tamsulosin is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), it has also been assessed in clinical studies for other conditions/symptoms and in other populations such as women and children. In this systematic review of randomized studies, the overall safety of tamsulosin was assessed, focusing on these understudied populations. Literature searches were conducted using Embase, Medline, and PubMed (inception-December 2015). A study was included if patients were randomized to receive treatment with any dose of tamsulosin capsules, tablets, or an oral controlled absorption system and numerical safety results were reported. Overall, 160 articles involving 46,072 participants met the inclusion criteria. Of these, four studies included women only and three included children. The mean [standard deviation (SD)] age ranged from 7.3 (4.2) to 76.8 (7.1) years. The studies (n; %) evaluated healthy subjects (18; 11%) or patients with lower urinary tract symptoms/BPH (90; 56%), ureteral stones/renal colic (42; 26%), prostatitis (4; 3%), or other conditions (6; 4%). Patients discontinued tamsulosin primarily because of adverse events (AEs) or insufficient response. AEs in women and children were abdominal pain, asthenia, constipation, dizziness, dry mouth, drowsiness, dyspepsia, headache, incontinence, nasal congestion, nausea, orthostatic hypotension, and somnolence. Due to heterogeneity across studies, statistical analysis could not be conducted. No unexpected AEs were observed in an all-comers population treated with tamsulosin for various conditions/symptoms. The overall safety profile in women and children seemed to be generally consistent with the profile in men, the indicated population.

Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard?

PubMed

Silva, João; Silva, Carlos Martins; Cruz, Francisco

2014-01-01

The pharmacological treatment of lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) is based on alpha-blockers and 5α-reductase inhibitors isolated or in combination. Silodosin, an alpha-1A specific alpha-blocker is the only innovation in these groups of agents. This classical paradigm is being challenged by antimuscarinics, 5-phosphodiesterase inhibitors (PDE5i) and β3-adrenoreceptor agonists. Silodosin is effective in reducing BPH/LUTS, including nocturia and shows little cardiovascular adverse events. Antimuscarinic drugs isolated or in combination with alpha-blockers improve storage symptoms without any harmful effect to the voiding function. PDE5i alone improve BPH/LUTS. Combination of PDE5i with alpha-blockers provides better symptomatic control than alpha-blockers alone. A recent head-to-head comparison of tadalafil 5 mg/day with tamsulosin 0.4 mg/day showed that these agents provided the same improvement in BPH/LUTS and, surprisingly, the same improvement in the urinary flow. In fact, previous studies with tadalafil had not shown any effect of tadalafil on flow. In addition, tadalafil but not tamsulosin improved sexual function. Mirabegron, the first β3-adrenoreceptor agonist, while improving BPH/LUTS in men with bladder outlet obstruction, do not decrease urinary flow or detrusor pressure. The standard medical treatment for BPH/LUTS is still based on alpha-blockers, 5ARIs or its combination. In the future, it is expected that BPH/LUTS treatment will become individualized, according to the type of symptoms, presence of sexual dysfunction and risk of BPH progression. This will challenge our concept of standard treatment for BPH/LUTS.

The effects of the combined use of a PDE5 inhibitor and medications for hypertension, lower urinary tract symptoms and dyslipidemia on corporal tissue tone.

PubMed

Lee, J H; Chae, M R; Park, J K; Jeon, J H; Lee, S W

2012-01-01

ED is closely associated with its comorbidities (hypertension, dyslipidemia and lower urinary tract symptoms (LUTS)). Therefore, several drugs have been prescribed simultaneously with PDE5 inhibitors. If a specific medication for ED comorbidities has enhancing effects on PDE5 inhibitors, it offers alternative combination therapy in nonresponders to monotherapy with PDE5 inhibitors and allows clinicians to treat ED and its comorbidities simultaneously. To establish theoretical basis of choosing an appropriate medication for ED and concomitant disease, we examined the effects combining a PDE5 inhibitor with representative drugs for hypertension, dyslipidemia and LUTS on relaxing the corpus cavernosum of rabbits using the organ-bath technique. The effect of mirodenafil on relaxing phenylephrine-induced cavernosal contractions was significantly enhanced by the presence of 10(-4) M losartan, 10(-6) M nifedipine, 10(-6) M amlodipine, 10(-7) M doxazosin and 10(-9) M tamsulosin (P<0.05). The maximum relaxation effects were 47.2±3.8%, 57.6±2.6%, 64.0±3.7%, 76.1±5.7% and 71.7±5.4%, respectively. Enalapril and simvastatin had no enhancing effects. The relaxation induced by sodium nitroprusside alone (39.0±4.0%) was significantly enhanced in the presence of the 10(-4) M losartan (66.0±6.0%, P<0.05). Tetraethylammonium (1 mM) significantly inhibited the enhancement effects of tamsulosin and doxazosin on mirodenafil-induced relaxation (doxazosin: 76.1±5.7% vs 45.3±2.3%; tamsulosin: 71.7±5.4% vs 48.1±3.5%). On the basis of these findings, losartan seemed to induce synergistic effects through an interaction with nitric oxide. In addition, K(+) channel activation could be one of the mechanisms for the synergistic effect of combining mirodenafil with doxazosin or tamsulosin. We believe that the combination of a PDE5 inhibitor with losartan, nifedipine, amlodipine, doxazosin or tamsulosin could be a pharmacologic strategy for simultaneously treating ED and its comorbidities and increasing response rates to PDE5 inhibitors.

[Intraoperative floppy iris syndrome].

PubMed

Mazal, Z

2007-04-01

In the year 2005, Chang and Cambell described unusual reaction of the iris during the cataract surgery in patients treated with tamsulosine. This was named as IFIS, an acronym for the Intraoperative Floppy Iris Syndrome. In its advanced stage, the syndrome is characterized by insufficient mydfiasis before the surgery, narrowing of the pupil during the surgery, its impossible dilatation during the surgery by means of stretching, unusual elasticity of the pupilar margin, surging and fluttering iris with tendency to prolapse. The same manifestations we observed in our patients and we confirm the direct connection with tamsulosine hydrochloride treatment. Tamsulosine is the antagonist of alpha 1A adrenergic receptors whose are present, except in the smooth musculature of the prostate gland and the urinary bladder, in the iris dilator as well. At the same time we observed this syndrome rarely in some patients not using tamsulosine. In most cases, these patients were treated with antipsychotic drugs.

Comparison of Prophylactic Naftopidil, Tamsulosin, and Silodosin for {sup 125}I Brachytherapy-Induced Lower Urinary Tract Symptoms in Patients With Prostate Cancer: Randomized Controlled Trial

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

Tsumura, Hideyasu, E-mail: sugan@pd5.so-net.ne.jp; Satoh, Takefumi; Ishiyama, Hiromichi

2011-11-15

Purpose: To compare the efficacy of three {alpha}{sub 1A}/{alpha}{sub 1D}-adrenoceptor (AR) antagonists-naftopidil, tamsulosin, and silodosin-that have differing affinities for the {alpha}{sub 1}-AR subtypes in treating urinary morbidities in Japanese men with {sup 125}I prostate implantation (PI) for prostate cancer. Methods and Materials: This single-institution prospective randomized controlled trial compared naftopidil, tamsulosin, and silodosin in patients undergoing PI. Patients were randomized and received either naftopidil, tamsulosin, or silodosin. Treatment began 1 day after PI and continued for 1 year. The primary efficacy variables were the changes in total International Prostate Symptom Score (IPSS) and postvoid residual urine (PVR). The secondary efficacymore » variables were changes in IPSS storage score and IPSS voiding score from baseline to set points during the study (1, 3, 6, and 12 months). Results: Two hundred twelve patients were evaluated in this study between June 2006 and February 2009: 71, 70, and 71 patients in the naftopidil, tamsulosin, and silodosin groups, respectively. With respect to the primary efficacy variables, the mean changes in the total IPSS at 1 month after PI in the naftopidil, tamsulosin, and silodosin groups were +10.3, +8.9, and +7.5, respectively. There were significantly greater decreases with silodosin than naftopidil at 1 month in the total IPSS. The mean changes in the PVR at 6 months were +14.6, +23.7, and +5.7 mL in the naftopidil, tamsulosin, and silodosin groups, respectively; silodosin showed a significant improvement in the PVR at 6 months vs. tamsulosin. With respect to the secondary efficacy variables, the mean changes in the IPSS voiding score at 1 month in the naftopidil, tamsulosin, and silodosin groups were +6.5, +5.6, and +4.5, respectively; silodosin showed a significant improvement in the IPSS voiding score at 1 month vs. naftopidil. Conclusions: Silodosin has a greater impact on improving PI-induced lower urinary tract symptoms than the other two agents.« less

Comparison of Murraya koenigii- and Tribulus terrestris-based oral formulation versus tamsulosin in the treatment of benign prostatic hyperplasia in men aged >50 years: a double-blind, double-dummy, randomized controlled trial.

PubMed

Sengupta, Gairik; Hazra, Avijit; Kundu, Anup; Ghosh, Anirban

2011-12-01

Drug treatment can defer surgical intervention in benign prostatic hyperplasia (BPH), a common disorder in elderly men, and is widely practiced. Various herbal formulations have been used for the treatment of BPH, but few have been compared with established modern medicines in head-to-head clinical trials. We compared the effectiveness and tolerability of an oral formulation, comprising standardized extracts of Murraya koenigii and Tribulus terrestris leaves being marketed in India under Ayurvedic license, versus tamsulosin in the treatment of symptomatic BPH. A double-blind, double-dummy, parallel-group, randomized controlled trial was conducted with treatment-naive ambulatory patients with BPH aged >50 years. Patients received either the plant drug in a dose of 2 capsules BID or tamsulosin 400 μg once daily for 12 weeks with 2 interim follow-up visits at the end of 4 and 8 weeks. The double-dummy technique was used to ensure double-blinding. The primary effectiveness measure was reduction in the International Prostate Symptom Score (IPSS). Proportion of patients becoming completely or relatively symptom free (IPSS <8), change in prostate volume (assessed by using ultrasonography conducted by a radiologist blinded to the nature or duration of treatment), and peak urinary flow rate (assessed by using uroflowmetry) were secondary measures. Treatment-emergent adverse events, changes in weight, vital signs, and routine laboratory safety parameters were recorded. Forty-six patients were randomized (23 per group); 19 completed all study visits in the plant drug group and 21 in the tamsulosin group. However, applying modified intention-to-treat criterion, 23 and 21 patients, respectively, were considered for effectiveness analysis. Mean (SD) age and baseline weight were 58.5 (14.0) years and 57.5 (10.5) kg in the plant drug arm, and 62.9 (6.3) years and 59.8 (9.9) kg in the tamsulosin arm, respectively. Median (interquartile range) symptom duration was 12.0 (12.0-24.0) months and 15.0 (12.0-24.0) months, respectively, in the 2 arms. These differences were not statistically significant. IPSS (median [interquartile range]) declined from 17.0 (12.0-19.0) to 9.0 (5.0-13.0) with the plant drug and from 14.0 (11.0-18.0) to 8.0 (6.0-13.0) with tamsulosin after 12 weeks of treatment. The decline was individually significant in both groups (both, P < 0.001), but intergroup values showed no statistically significant difference at any point of time. IPSS <8 at study end was achieved by 10 and 7 patients, respectively, in the 2 arms (P = 0.548). The plant drug reduced prostate volume from 33.5 (26.2-45.9) mL to 31.6 (26.1-37.5) mL (P = 0.040). The corresponding reduction with tamsulosin, from 41.3 (29.4-51.3) mL to 39.9 (32.6-52.3) mL, was not statistically significant. Peak urinary flow rate did not change appreciably. Mild joint pain was the most common adverse event in both arms. No serious events were encountered. Compliance was satisfactory. These findings suggest that the M koenigii- and T terrestris-based formulation significantly lowered IPSS scores in the initial treatment of symptomatic BPH. Further trials are needed to determine if the beneficial effect is sustained beyond the 12-week observation period of this trial. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

[Management of ureteric colic with ketorolac and nifedipin vs. ketorolac and tamsulosin in the emergency room].

PubMed

Montiel-Jarquín, Álvaro J; Rocha-Rocha, Valeria M; Solís-Mendoza, Hugo A; Romero-Figueroa, María S; Etchegaray-Morales, Ivet; Alvarado-Ortega, Ivan

2017-01-01

Ureteric colic is the most common symptom of lithiasis. It is caused by the presence of stones accumulated in the renal papillae. These stones often migrate down the ureter, causing a ureteric colic, characterized by a severe pain in the lumbar region. The aim of this study was to compare the use of ketorolac and nifedipine vs. ketorolac and tamsulosin for the medical treatment of pain caused by stones in the lower ureter. Longitudinal study of 150 patients of 21-years or older with stones in the lower third of the ureter. 50% received ketorolac and nifedipine and the other 50%, ketorolac and tamsulosin. The Numeric Pain Rating Scale (NPRS) was used for the assessment of pain at admission and 4 and 12 hours after the treatment was administered. We used descriptive and inferential statistics (Mann-Whitney-Wilcoxon, chi-squared and Poisson regression). Mean age was 38.17 years; 54.7% were male and 45.3% female. NPRS mean was 9.69 (initially), 7.42 (at 4 hours) and 2.05 (at 12 hours). There were no significant differences in the initial measurement of pain between groups (p < 0.005); four and 12 hours later the pain decreased more in patients managed with ketorolac and nifedipine, p = 0.0041. There were no complications nor side effects in both treatments. The use of ketorolac and nifedipine is more effective than the use of ketorolac and tamsulosin for the management of pain caused by lower ureteral colic during the first 12 hours of treatment.

Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

PubMed

Haddad, Lisette; Corriveau, Stéphanie; Rousseau, Eric; Blouin, Simon; Pasquier, Jean-Charles; Ponsot, Yves; Roy-Lacroix, Marie-Ève

2018-01-01

To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 μM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 μM for tamsulosin and 1 μM for nifedipine when calculated as the AUC as compared to DMSO controls. Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

Assessment of tamsulosin as a potential male contraceptive in healthy volunteers.

PubMed

Wang, Jin; Zhao, Yong; Jiang, Shao-bo; Xia, Qing-hua; Wei, Chun-xiao; Wang, Mu-wen; Sun, Peng; Jin, Xun-bo

2012-09-01

To investigate the efficacy and safety of tamsulosin, an α(1A)-adrenoceptor antagonist, as a potential male contraceptive. Forty healthy male volunteers were equally divided into 2 groups, each of which received placebo and tamsulosin sequentially in a crossover manner. Ejaculatory profile was examined 4 to 6 hours after administration and adverse effects were noted. Anejaculation occurred in all subjects after taking 0.8-mg of tamsulosin. Total functional sperm count was significantly reduced in subjects after taking 0.4-mg of tamsulosin. Six subjects receiving 0.8-mg of tamsulosin complained of tolerated discomfort, which disappeared 10 hours after administration. When administered at 0.8 mg, tamsulosin can cause anejaculation with some transient side effects. Our results imply that tamsulosin and related drugs might potentially be used as male contraceptive agents in the future, which needs more studies to verify. Copyright © 2012 Elsevier Inc. All rights reserved.

Tamsulosin hydrochloride vs placebo for management of distal ureteral stones: a multicentric, randomized, double-blind trial.

PubMed

Vincendeau, Sébastien; Bellissant, Eric; Houlgatte, Alain; Doré, Bertrand; Bruyère, Franck; Renault, Alain; Mouchel, Catherine; Bensalah, Karim; Guillé, François

2010-12-13

α-Blockers induce selective relaxation of ureteral smooth muscle with subsequent inhibition of ureteral spasms and dilatation of the ureteral lumen. The aim of the study was to evaluate the efficacy and safety of the α-blocker tamsulosin hydrochloride in patients with ureteral colic owing to a distal ureteral stone. This was a multicenter, placebo-controlled, randomized, double-blind study. Patients with emergency admission for ureteral colic with a 2- to 7-mm-diameter radio-opaque distal ureteral stone were included in the study. They received tamsulosin (0.4 mg/d) or matching placebo until stone expulsion or day 42, whichever came first. The main end point was time to stone expulsion between inclusion and day 42. Sequential statistical analysis was performed using the triangular test. A total of 129 patients with acute renal colic were recruited from emergency wards between February 1, 2002, and December 8, 2006, in 6 French hospitals. Of these 129 randomized patients (placebo, 63; tamsulosin, 66), 7 were excluded from analyses: 5 for major deviations from inclusion criteria, 1 for stone expulsion before the first treatment administration, and 1 for consent withdrawal. At inclusion, mean (SD) stone diameters were 3.2 (1.2) and 2.9 (1.0) mm in the placebo and tamsulosin groups, respectively (P = .23). Expulsion delay distributions during 42 days did not show any difference (P = .30). The numbers of patients who spontaneously expelled their stone within 42 days were 43 of 61 (70.5%) and 47 of 61 (77.0%) in the placebo and tamsulosin groups, respectively (P = .41). Corresponding delays were 10.1 (10.0) and 9.6 (9.8) days (P = .82). Other secondary end points and tolerance were not different between groups. Although well tolerated, a daily administration of 0.4 mg of tamsulosin did not accelerate the expulsion of distal ureteral stones in patients with ureteral colic. clinicaltrials.gov Identifier: NCT00151567.

Tamsulosin reduces nighttime urine production in benign prostatic hyperplasia patients with nocturnal polyuria: a prospective open-label long-term study using frequency-volume chart.

PubMed

Kojima, Yoshiyuki; Sasaki, Shoichi; Imura, Makoto; Kubota, Yasue; Hayashi, Yutaro; Kohri, Kenjiro

2012-01-01

The effects of tamsulosin treatment on changes in frequency-volume chart (FVC) data, especially nighttime urine production, over time were assessed, and the mechanisms underlying the improvement of nocturia in benign prostatic hyperplasia (BPH) patients with nocturnal polyuria (NP) are discussed. A total of 104 patients with lower urinary tract symptoms secondary to BPH were enrolled. After enrollment in the study, the patients were treated with tamsulosin (0.2 mg) once daily. Visits were scheduled every 4 weeks until week 12 (month 3) after study entry, and then every 12 weeks subsequently. All patients completed the International Prostate Symptom Score (IPSS), quality of life (QOL) index, and 3-day FVC, and underwent uroflowmetry at enrollment and on each visit. Eighty-two patients (mean age: 70.9 ± 7.1 years) were analyzed for 24 months after treatment. Patients were divided into two groups, NP and nonNP, based on FVC outcome. The IPSS, QOL index, and maximum flow rate improved during the 24-month period after treatment in both groups. Mean daytime urine volume significantly increased in the NP group, but no changes were detected in the nonNP group. Mean nighttime urine frequency significantly decreased in the NP group over a 24-month period, and was associated with a significant decrease in nighttime urine volume that was not found in the nonNP group. Maximum voided volume increased most months after treatment in both groups. The present long-term prospective study using FVC demonstrated that tamsulosin reduced nighttime urine production in BPH patients with NP. Copyright © 2011 Wiley Periodicals, Inc.

Comparison and Efficacy of Low-Dose and Standard-Dose Tamsulosin and Alfuzosin in Medical Expulsive Therapy for Lower Ureteral Calculi: Prospective, Randomized, Comparative Study

PubMed Central

Cha, Woo Heon; Choi, Jae Duck; Seo, Young Jin; Lee, Kyungseop

2012-01-01

Purpose Typically in Korea, for a standard dose (0.4 mg) of tamsulosin, two low doses (0.2 mg) are administered. The aim of this study was to evaluate and compare the efficacy of tamsulosin (0.2 mg and 0.4 mg) and alfuzosin (10 mg) in the treatment of lower ureteral stones. Materials and Methods A total of 141 patients presenting with a single 4- to 10-mm sized lower ureteral stone were randomly assigned to 4 groups. Patients in group 1 (n=41) and group 2 (n=30) received an oral dose of 0.2 mg tamsulosin once and twice daily, respectively, and patients in group 3 (n=36) received a daily oral dose of 10 mg alfuzosin. Patients in group 4 (n=34) received trospium chloride only. The spontaneous passage of stones, the stone expulsion time, and adverse effects were evaluated. Results There were no significant differences in patient background, including age, sex, BMI, stone size, stone side, and symptom duration. The spontaneous stone passage rate through the ureter was higher and the stone expulsion time was faster in groups 1, 2, and 3 than in group 4. There were no statistically different changes in groups 1, 2, and 3. The adverse effects observed in all groups were comparable and were mild. Conclusions Tamsulosin at 0.2 mg and 0.4 mg and alfuzosin (10 mg) proved to be safe and effective. A first cycle of medical expulsive therapy with tamsulosin 0.2 mg could be considered as an option in the management of single lower ureteral stone. PMID:22670195

Efficacy and safety of tamsulosin as a medical expulsive therapy for stones in children.

PubMed

Aldaqadossi, Hussein A; Shaker, Hossam; Saifelnasr, Mohammed; Gaber, Mohammed

2015-06-01

To evaluate the efficacy of tamsulosin for promoting ureteric stone expulsion in children, based on the confirmed efficacy of tamsulosin as a medical expulsive therapy in adults. From February 2010 to July 2013, 67 children presenting with a distal ureteric stone of <1 cm as assessed on unenhanced computed tomography were included in the study. The patients were randomised into two groups, with group 1 (33 patients) receiving tamsulosin 0.4 mg and ibuprofen, and group 2 (34) receiving ibuprofen only. They were followed up for 4 weeks. Endoscopic intervention was indicated for patients with uncontrolled pain, recurrent urinary tract infection, hypersensitivity to tamsulosin and failure of stone passage after 4 weeks of conservative treatment. Sixty-three patients completed the study. There were no statistically significant differences between the groups in patient age, body weight and stone size, the mean (SD) of which was 6.52 (1.8) mm in group 1 vs. 6.47 (1.79) mm in group 2 (P = 0.9). The mean (SD) time to stone expulsion in group 1 was 7.7 (1.9) days, vs. 18 (1.73) days in group 2 (P < 0.001). The analgesic requirement (mean number of ketorolac injections) in group 1 was significantly less than in group 2, at 0.55 (0.8) vs. 1.8 (1.6) (P < 0.001). The stone-free rate was 87% in group 1 and 63% in group 2 (P = 0.025). Tamsulosin used as a medical expulsive therapy for children with ureteric stones is safe and effective, as it facilitates spontaneous expulsion of the stone.

Alpha 1-Adrenoceptor Blocker May Improve Not Only Voiding But Also Storage Lower Urinary Tract Symptoms Caused by 125I Brachytherapy for Prostate Cancer

PubMed Central

Aoki, Yoshitaka; Ito, Hideaki; Miwa, Yoshiji; Akino, Hironobu; Shioura, Hiroki; Kimura, Hirohiko; Yokoyama, Osamu

2014-01-01

Purpose. To assess changes in lower urinary tract symptoms (LUTS) within 1 year after brachytherapy in patients receiving alpha 1-adrenoceptor antagonists. Methods. We retrospectively evaluated 116 patients who underwent 125I prostate brachytherapy in our institute. Seventy-one patients were treated with a combination of external beam radiation therapy and brachytherapy. Alpha 1-adrenoceptor antagonists were prescribed to all patients after brachytherapy. International Prostate Symptom Score (IPSS) forms and postvoid residual urine volume were recorded at all follow-up visits. Results. Forty-nine patients were given tamsulosin hydrochloride, 32 were given silodosin hydrochloride, and 35 were given naftopidil for up to 6 months after seed implantation. Patients given tamsulosin or naftopidil tended to show a higher peak IPSS and slower recovery to baseline values than those given silodosin. The patients given naftopidil showed an insufficient recovery in storage symptoms in naftopidil group in comparison with tamsulosin group at 3 months and with silodosin group at 6 and 9 months. Conclusions. In the management of LUT after brachytherapy, silodosin may provide a more favorable improvement. Silodosin and tamsulosin may have an advantage in improving not only voiding but also storage lower urinary tract symptoms after brachytherapy. PMID:25006516

Ten years of intraoperative floppy iris syndrome in the era of α-blockers

PubMed Central

Mohamad Al-Ali, Badereddin; Radmayr, Christian; Weber, Maria; Horninger, Wolfgang; Findl, Oliver; Plas, Eugen

2017-01-01

Introduction The use of alpha-1 receptor antagonists in the treatment of benign prostatic hyperplasia (BPH) has created a problem in ophthalmic surgery, the so-called intraoperative floppy iris syndrome (IFIS). This consists of a billowing iris, insufficient pupillary dilation with progressive intraoperative miosis, and protrusion of iris tissue through the tunnel and side port incision that are made for access to the anterior chamber during surgery. IFIS presents particular difficulties in cataract surgery which is carried out through the pupil with manipulations in the immediate vicinity of the iris. The complications range from poor visibility of the operative field to iris damage with the surgical instruments and to rupture of the posterior capsule, with loss of lens material into the vitreous body. Material and methods A comprehensive literature review was performed using MEDLINE with MeSH terms and keywords ‘benign prostatic hyperplasia’, ‘intraoperative floppy iris syndrome’, ‘adrenergic alpha-antagonist’ and ‘cataract surgery’. In addition, reference lists from identified publications were reviewed to identify reports and studies of interest from 2001 to 2017. Results The A total of 95% of experienced ophthalmologic surgeons reported that systematic treatment with tamsulosin represents a challenging surgical condition increasing the risk of complications. Alpha-blockers are commonly prescribed, with 1,079,505 packages of tamsulosin prescribed each month in 2014 in Austria. Dose modification may be one way to reduce the risk of IFIS. A lower incidence of IFIS was reported in patients on tamsulosin in Japan, but the recommended dosage was lower than that used in Europe and the US (0.2 mg vs. 0.4 mg). Conclusions We showed that not all patients taking tamsulosin experience IFIS. Moreover, larger investigations with a prospective design are needed, including studies to monitor the pre- and post-therapeutic ophthalmologic changes under tamsulosin, as well as urodynamic improvements resulting from this therapy. PMID:29732214

Tamsulosin

MedlinePlus

... bladder emptying), painful urination, and urinary frequency and urgency. Tamsulosin is in a class of medications called ... that tamsulosin may cause dizziness, lightheadedness, a spinning sensation, and fainting, especially when you get up too ...

Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland.

PubMed

Chakrabarty, Basu; Dey, Anupa; Lam, Michelle; Ventura, Sabatino; Exintaris, Betty

2015-06-01

To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland. The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques. Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs. This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia. © 2014 Wiley Periodicals, Inc.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications. Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation. This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. Methods/design The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo. Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. Trial registration ISRCTN69423238; EudraCT number: 2010-019469-26 PMID:24947817

Use of drug therapy in the management of symptomatic ureteric stones in hospitalized adults (SUSPEND), a multicentre, placebo-controlled, randomized trial of a calcium-channel blocker (nifedipine) and an α-blocker (tamsulosin): study protocol for a randomized controlled trial.

PubMed

McClinton, Sam; Starr, Kathryn; Thomas, Ruth; McLennan, Graeme; McPherson, Gladys; McDonald, Alison; Lam, Thomas; N'Dow, James; Kilonzo, Mary; Pickard, Robert; Anson, Ken; Burr, Jennifer

2014-06-20

Urinary stone disease is common, with an estimated prevalence among the general population of 2% to 3%. Ureteric stones can cause severe pain and have a significant impact on quality of life, accounting for over 15,000 hospital admissions in England annually. Uncomplicated cases of smaller stones in the lower ureter are traditionally treated expectantly. Those who fail standard care or develop complications undergo active treatment, such as extracorporeal shock wave lithotripsy or ureteroscopy with stone retrieval. Such interventions are expensive, require urological expertise and carry a risk of complications.Growing understanding of ureteric function and pathophysiology has led to the hypothesis that drugs causing relaxation of ureteric smooth muscle, such as the selective α-blocker tamsulosin and the calcium-channel blocker nifedipine, can enhance the spontaneous passage of ureteric stones. The use of drugs in augmenting stone passage, reducing the morbidity and costs associated with ureteric stone disease, is promising. However, the majority of clinical trials conducted to date have been small, poor to moderate quality and lacking in comprehensive economic evaluation.This trial aims to determine the clinical and cost-effectiveness of tamsulosin and nifedipine in the management of symptomatic urinary stones. The SUSPEND (Spontaneous Urinary Stone Passage ENabled by Drugs) trial is a multicentre, double-blind, randomized controlled trial evaluating two medical expulsive therapy strategies (nifedipine or tamsulosin) versus placebo.Patients aged 18 to 65 with a ureteric stone confirmed by non-contrast computed tomography of the kidney, ureter and bladder will be randomized to receive nifedipine, tamsulosin or placebo (400 participants per arm) for a maximum of 28 days. The primary clinical outcome is spontaneous passage of ureteric stones at 4 weeks (defined as no further intervention required to facilitate stone passage). The primary economic outcome is a reduction in the incremental cost per quality-adjusted life years, determined at 12 weeks. The analysis will be based on all participants as randomized (intention to treat). The trial has 90% power with a type I error rate of 5% to detect a 10% increase in primary outcome between the tamsulosin and nifedipine treatment groups. ISRCTN69423238; EudraCT number: 2010-019469-26.

Medical impulsive therapy (MIT): the impact of 1 week of preoperative tamsulosin on deployment of 16-French ureteral access sheaths without preoperative ureteral stent placement.

PubMed

Kaler, Kamaljot S; Safiullah, Shoaib; Lama, Daniel J; Parkhomenko, Egor; Okhunov, Zhamshid; Ko, Young H; Huynh, Linda; Patel, Roshan M; Landman, Jaime; Clayman, Ralph V

2018-05-25

Medical expulsive therapy is based on pharmacologic ureteral relaxation. We hypothesized this concept may facilitate the deployment of the large 16 French (F) ureteral access sheath (UAS) when patients are intentionally pre-treated with oral tamsulosin, i.e., medical impulsive therapy. We retrospectively analyzed our experience with UAS deployment during endoscopic-guided percutaneous nephrolithotomy in prone position in patients pre-treated for 1 week with oral tamsulosin with a contemporary untreated cohort. Between January 2015 and September 2016, seventy-seven patients without a pre-existing ureteral stent met inclusion criteria. Demographic data, tamsulosin usage, UAS size, deployment failure, ureteral injuries, stone-free rates, and complications were recorded. Univariate and multivariate analysis was conducted to assess the impact of tamsulosin on deployment of the 16F UAS. There was no statistical difference between the tamsulosin (n = 40) group and non-tamsulosin (n = 37) group in regard to demographic data. The tamsulosin group had a significantly higher percentage of 16F UAS deployment, 87 vs. 43% (p < 0.001), and no significant difference in ureteral injuries (p = 0.228). Univariate and multivariate analysis revealed that tamsulosin significantly increased the odds ratio (9.3 and 19.4, respectively) for successful passage of a 16F UAS. Despite a larger stone volume, there was no significant difference in computed tomography scan complete stone-free rates (29 vs. 42%; p = 0.277) at median post-operative time of only 3 days. In this retrospective study, 1 week of preoperative tamsulosin was associated with an increase in the deployment of a 16F UAS in patients without preoperative ureteral stent placement.

Use of drug therapy in the management of symptomatic ureteric stones in hospitalised adults: a multicentre, placebo-controlled, randomised controlled trial and cost-effectiveness analysis of a calcium channel blocker (nifedipine) and an alpha-blocker (tamsulosin) (the SUSPEND trial).

PubMed

Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Kilonzo, Mary; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; Norrie, John; McPherson, Gladys; McDonald, Alison; Shearer, Kirsty; Gillies, Katie; Anson, Kenneth; Boachie, Charles; N'Dow, James; Burgess, Neil; Clark, Terry; Cameron, Sarah; McClinton, Samuel

2015-08-01

Ureteric colic, the term used to describe the pain felt when a stone passes down the ureter from the kidney to the bladder, is a frequent reason for people to seek emergency health care. Treatment with the muscle-relaxant drugs tamsulosin hydrochloride (Petyme, TEVA UK Ltd) and nifedipine (Coracten(®), UCB Pharma Ltd) as medical expulsive therapy (MET) is increasingly being used to improve the likelihood of spontaneous stone passage and lessen the need for interventional procedures. However, there remains considerable uncertainty around the effectiveness of these drugs for routine use. To determine whether or not treatment with either tamsulosin 400 µg or nifedipine 30 mg for up to 4 weeks increases the rate of spontaneous stone passage for people with ureteric colic compared with placebo, and whether or not it is cost-effective for the UK NHS. A pragmatic, randomised controlled trial comparing two active drugs, tamsulosin and nifedipine, against placebo. Participants, clinicians and trial staff were blinded to treatment allocation. A cost-utility analysis was performed using data gathered during trial participation. Urology departments in 24 UK NHS hospitals. Adults aged between 18 and 65 years admitted as an emergency with a single ureteric stone measuring ≤ 10 mm, localised by computerised tomography, who were able to take trial medications and complete trial procedures. Eligible participants were randomised 1 : 1 : 1 to take tamsulosin 400 µg, nifedipine 30 mg or placebo once daily for up to 4 weeks to make the following comparisons: tamsulosin or nifedipine (MET) versus placebo and tamsulosin versus nifedipine. The primary effectiveness outcome was the proportion of participants who spontaneously passed their stone. This was defined as the lack of need for active intervention for ureteric stones at up to 4 weeks after randomisation. This was determined from 4- and 12-week case-report forms completed by research staff, and from the 4-week participant self-reported questionnaire. The primary economic outcome was the incremental cost per quality-adjusted life-year (QALY) gained over 12 weeks. We estimated costs from NHS sources and calculated QALYs from participant completion of the European Quality of Life-5 Dimensions health status questionnaire 3-level response (EQ-5D-3L™) at baseline, 4 weeks and 12 weeks. Primary outcome analysis included 97% of the 1167 participants randomised (378/391 tamsulosin, 379/387 nifedipine and 379/399 placebo participants). The proportion of participants who spontaneously passed their stone did not differ between MET and placebo [odds ratio (OR) 1.04, 95% confidence interval (CI) 0.77 to 1.43; absolute difference 0.8%, 95% CI -4.1% to 5.7%] or between tamsulosin and nifedipine [OR 1.06, 95% CI 0.74 to 1.53; absolute difference 1%, 95% CI -4.6% to 6.6%]. There was no evidence of a difference in QALYs gained or in cost between the trial groups, which means that the use of MET would be very unlikely to be considered cost-effective. These findings were unchanged by extensive sensitivity analyses around predictors of stone passage, including sex, stone size and stone location. Tamsulosin and nifedipine did not increase the likelihood of stone passage over 4 weeks for people with ureteric colic, and use of these drugs is very unlikely to be cost-effective for the NHS. Further work is required to investigate the phenomenon of large, high-quality trials showing smaller effect size than meta-analysis of several small, lower-quality studies. Current Controlled Trials ISRCTN69423238. European Clinical Trials Database (EudraCT) number 2010-019469-26. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 63. See the NIHR Journals Library website for further project information.

The Role of the Tamsulosin in the Medical Expulsion Therapy for Distal Ureteral Stones

PubMed Central

Nuraj, Petrit; Hyseni, Nexhmi

2017-01-01

Background: This research aims to evaluate the role of tamsulosin in the medical expulsion therapy for distal ureteral stones, including her effects in stone expulsion time, expulsion rates, stone size, pain episodes and analgesic dosage usage. Material and methods: The 104 patients with distal ureteral calculi were examined, with the size of the stones 4-10 mm. They were randomly divided into two groups: study group (n=52), received tamsulosin 0.4 mg in morning, for 28 days, analgesic (diclofenac 75 mg), high fluid intake and Control group (n=52) received analgesic (diclofenac 75 mg), high fluid intake. Results: There is no significant difference between groups, based on sex (P=0.835) and age (P=0.987). Average size of the stones was 6.5 mm (SD ± 1.6 mm), with no significant difference (P=0.996). Stone expulsion rate is 90.4% in the study group and 71.2% from the control group, with statistical significance (P=0.023). The average time of the expulsion of stones in the study group was 9.6 days (SD ± 7.1 days), control group 13.7 days (SD ± 7.3 days), with statistical significance, (P=0.034). Average dose of analgesics in the study group was 63.7 mg (SD ± 45.2 mg), control group is 109.2 (SD ± 53.3), with statistical significance (P=0.019). Conclusion: Our study reveals that tamsulosin is efficient for the treatment of distal ureteral stones. Tamsulosin decrease the number of ureteral colic episodes, by acting as a spasmolytic, increase and hasten stone expulsion rates, reduce days of stone expulsion, decrease analgesic dose usage. PMID:28790547

The effect of competing direct-to-consumer advertising campaigns on the use of drugs for benign prostatic hyperplasia: time series analysis.

PubMed

Skeldon, Sean C; Kozhimannil, Katy B; Majumdar, Sumit R; Law, Michael R

2015-04-01

Direct-to-consumer advertising (DTCA) remains a controversial issue, with concerns that it leads to unnecessary and inappropriate prescribing. Whether DTCA shifts prescribing from first-line (guideline-recommended) therapy to second-line drugs has not been studied. The purpose of this study was to determine the impact of sequential DTCA campaigns for two drugs used to treat benign prostatic hyperplasia (BPH): one newer agent, dutasteride (Avodart(®)), and one older first-line agent, tamsulosin (Flomax(®)). Interrupted time series analysis was used to assess the impact of each DTCA campaign using data on consumer "response" from Google Trends and dispensed prescriptions from IMS Health. We analyzed data for the United States from January 2003 to December 2007. DTCA for dutasteride and tamsulosin commenced on July, 2005 and April, 2006, respectively. Monthly Internet search volume (scaled from 0 to 100) for the advertised trade name of each drug and monthly U.S. prescription rates per 1,000 population were analyzed. The dutasteride campaign was associated with an increase in Internet searches for both "Avodart" (level change +31.3 %, 95 % CI: 27.2-35.4) and "Flomax" (level change +8.3 %, 95 % CI: 0.9-15.7), whereas the tamsulosin campaign was associated with increased "Flomax" searches (level change +25.3 %, 95 % CI: 18.7-31.8). The dutasteride campaign was associated with an increase in the prescription of dutasteride (trend = 0.45/month, 95 % CI: 0.33-0.56), but a larger impact was observed with tamsulosin prescriptions (trend = 0.76/month, 95 % CI: 0.02-1.50). Similarly, the tamsulosin campaign was associated with an immediate fourfold increase in the prescribing of tamsulosin (level change +5.76 units, 95 % CI: 1.79-9.72) compared to dutasteride (level change +1.47 units, 95 % CI: 0.79-2.14). DTCA was associated with the utilization of drugs to treat symptomatic BPH. However, both campaigns were associated with greater increases in the use of the guideline-recommended first-line agent. DTCA campaigns may increase the overall levels of guideline-recommended treatments to a greater extent than the specific advertised agents.

A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of rasagiline and tamsulosin.

PubMed

Brenna, Davide; Pirola, Margherita; Raimondi, Laura; Burke, Anthony J; Benaglia, Maurizio

2017-12-01

The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

α1-Blockers for the treatment of recurrent urinary tract infections in women with dysfunctional voiding: a prospective randomized study.

PubMed

Minardi, Daniele; Pellegrinelli, Francesco; Conti, Alessandro; Fontana, Donatella; Mattia, Michela; Milanese, Giulio; Muzzonigro, Giovanni

2015-01-01

To evaluate the therapeutic effects of tamsulosin on recurrent urinary tract infections in women with dysfunctional voiding. A total of 155 women with recurrent urinary tract infections and dysfunctional voiding were included and randomly assigned to the following groups: uroflowmetry biofeedback (group 1), α1-adrenoceptor antagonists (group 2), uroflowmetry biofeedback combined with α1-adrenoceptor antagonists (group 3) and no treatment (group 4). Patients were evaluated by the American Urological Association Symptom Index at 3, 6 and 12 months. Urodynamics was carried out in patients of groups 1, 2, and 3 at 3, 6 and 12 months, whereas urodynamics was only carried out at 12 months in group 4. All patients were followed up for 1 year with monthly urine cultures. The incidence of storage and emptying symptoms decreased significantly at 3, 6 and 12 months. Mean flow rate, flow time and voiding volume increased significantly (with a better outcome in patients of group 3), whereas post-void residual urine decreased. Mean opening detrusor pressure and detrusor pressure at maximum flow decreased significantly (with a better outcome in patients of group 3). Mean urethral closure pressure and maximum urethral closure pressure decreased significantly with a more significant decrease for patients in group 3. The prevalence of urinary tract infection decreased significantly in all groups after treatment, and this decrease remained stable during the follow up. In women with dysfunctional voiding and recurrent urinary tract infection, tamsulosin associated with uroflowmetry biofeedback might be an effective and safe treatment option for improving urinary symptoms and quality of life. © 2014 The Japanese Urological Association.

Naftopidil for the treatment of urinary symptoms in patients with benign prostatic hyperplasia

PubMed Central

Masumori, Naoya

2011-01-01

Naftopidil, approved only in Japan, is an α1-adrenergic receptor antagonist (α1-blocker) used to treat lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Different from tamsulosin hydrochloride and silodosin, in that it has higher and extremely higher affinity respectively, for the α1A-adrenergic receptor subtype than for the α1D type, naftopidil has distinct characteristics because it has a three times greater affinity for the α1D-adrenergic receptor subtype than for the α1A subtype. Although well-designed large-scale randomized controlled studies are lacking and the optimal dosage of naftopidil is not always completely determined, previous reports from Japan have shown that naftopidil has superior efficacy to a placebo and comparable efficacy to other α1-blockers such as tamsulosin. On the other hand, the incidences of ejaculatory disorders and intraoperative floppy iris syndrome induced by naftopidil may be lower than for tamsulosin and silodosin having high affinity for the α1A-adrenergic receptor subtype. However, it remains unknown if the efficacy and safety of naftopidil in Japanese is applicable to white, black and Hispanic men having LUTS/BPH in western countries. PMID:21753885

Silodosin is effective for treatment of LUTS in men with BPH: a systematic review

PubMed Central

Ding, Hui; Du, Wan; Hou, Zi-Zhen; Wang, Han-Zhang; Wang, Zhi-Ping

2013-01-01

The aim of this study was to systematically review the evidence on the efficacy and safety of silodosin treatments on lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH) from randomized controlled trials. We searched PubMed (1966–December 2011), Embase (1974–December 2011) and the Cochrane Library Database (2011, Issue 12). The assessed outcome measures were the change from baseline for the International Prostate Symptom Score (IPSS), quality of life (QoL) score, peak urine maximum flow rate (Qmax), QoL related to urinary symptoms and adverse effects. Two authors independently assessed the study quality and extracted data. All data were analysed using RevMan 5.1. The meta-analysis included four randomized controlled trials with a total of 2504 patients. The study durations were each 12 weeks. At the follow-up end points, the pooled results showed that the change from baseline for the silodosin group was significantly higher than the placebo group for the IPSS, QoL score and Qmax(mean difference (MD)=−2.78, P<0.00001; MD=−0.42, P=0.004; MD=1.17, P<0.00001,respectively) and patients felt more satisfied with QoL related to urinary symptoms in the silodosin group than the placebo group. Ejaculation disorder was the most commonly reported adverse effect. The pooled results also showed that the silodosin group was superior to the 0.2 mg tamsulosin group with respect to the IPSS and QoL score (IPSS: MD=−1.14, P=0.02; QoL score: MD=−0.26, P=0.02) and inferior to the 0.2 mg tamsulosin group with respect to Qmax (MD=−0.85, P=0.01). In contrast, there was no significant difference in the incidence of ejaculation disorder and dizziness between the silodosin and 0.2 mg tamsulosin groups. The current meta-analysis suggested that silodosin is an effective therapy for LUTS in men with BPH and is not inferior to 0.2 mg tamsulosin. PMID:23223034

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

PubMed

Pickard, Robert; Starr, Kathryn; MacLennan, Graeme; Lam, Thomas; Thomas, Ruth; Burr, Jennifer; McPherson, Gladys; McDonald, Alison; Anson, Kenneth; N'Dow, James; Burgess, Neil; Clark, Terry; Kilonzo, Mary; Gillies, Katie; Shearer, Kirsty; Boachie, Charles; Cameron, Sarah; Norrie, John; McClinton, Samuel

2015-07-25

Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 μg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). Tamsulosin 400 μg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. UK National Institute for Health Research Health Technology Assessment Programme. Copyright © 2015 Pickard et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

Tadalafil once daily improves ejaculatory function, erectile function, and sexual satisfaction in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia and erectile dysfunction: results from a randomized, placebo- and tamsulosin-controlled, 12-week double-blind study.

PubMed

Giuliano, François; Oelke, Matthias; Jungwirth, Andreas; Hatzimouratidis, Konstantinos; Watts, Steven; Cox, David; Viktrup, Lars

2013-03-01

Tadalafil, a long-acting phosphodiesterase type 5 inhibitor, is approved for treating signs and symptoms of benign prostatic hyperplasia (BPH) and erectile dysfunction (ED); tamsulosin, an alpha-blocker, is approved for treating signs and symptoms of BPH. To determine the effects of tadalafil or tamsulosin on sexual function, including ejaculation and orgasm, satisfaction, and erectile function, in sexually active men with ED and lower urinary tract symptoms suggestive of BPH (LUTS/BPH). A randomized, double-blind, placebo-controlled study of tadalafil 5 mg once daily for 12 weeks in men with LUTS/BPH; tamsulosin 0.4 mg once daily was an active control. The International Index of Erectile Function (IIEF) questionnaire was administered at baseline and 4, 8, and 12 weeks. Analysis of orgasm and ejaculation was post hoc based on the IIEF-Orgasmic Function (OF) domain (IIEF-Q9 [ejaculatory frequency] and Q10 [orgasmic frequency]). Other measures included IIEF-Intercourse Satisfaction (IS), Overall Satisfaction (OS), and Erectile Function (EF) domains. Changes from baseline to 12 weeks (or last observation) vs. placebo were analyzed using analysis of covariance. Higher IIEF scores indicate better functioning. Of 511 study participants, 310 (60.7%) had ED and were sexually active. The IIEF-OF increased significantly through 12 weeks with tadalafil vs. placebo (P = 0.048), as did IIEF-Q9 (P = 0.045) but not IIEF-Q10 (P = 0.100). Compared with placebo, IIEF-OF, Q9, and Q10 decreased significantly with tamsulosin (all P < 0.05). The IIEF-IS and OS increased significantly at end point with tadalafil (both P < 0.001); for tamsulosin, change was not significant for IS, while OS decreased significantly (P = 0.009). The IIEF-EF domain increased significantly vs. placebo with tadalafil (P < 0.001) but not tamsulosin (P = 0.699). Tadalafil 5 mg once daily significantly improved ejaculation and orgasm, intercourse and overall satisfaction, and erectile function. Men receiving tamsulosin 0.4 mg once daily experienced a decrease in both ejaculatory/orgasmic frequency and overall satisfaction vs. placebo, with no significant effect on erectile function. © 2013 International Society for Sexual Medicine.

Quantitation of tamsulosin in human plasma by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Din, Li; Li, Limin; Tao, Ping; Yang, Jin; Zhang, Zhengxing

2002-02-05

A highly sensitive method for quantitation of tamsulosin in human plasma using 1-(2,6-dimethyl-3-hydroxylphenoxy)-2-(3,4-methoxyphenylethylamino)-propane hydrochloride as the internal standard (I.S.) was established using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). After alkalization with saturated sodium bicarbonate, plasma were extracted by ethyl acetate and separated by HPLC on a C18 reversed-phase column using a mobile phase of methanol-water-acetic acid-triethylamine (620:380:1.5:1.5, v/v). Analytes were quantitated using positive electrospray ionization in a quadrupole spectrometer. LC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at m/z 228 for tamsulosin and m/z 222 for the I.S. Calibration curves, which were linear over the range 0.2-30 ng/ml, were analyzed contemporaneously with each batch of samples, along with low (0.5 ng/ml), medium (3 ng/ml) and high (30 ng/ml) quality control samples. The intra- and inter-assay variability ranged from 2.14 to 8.87% for the low, medium and high quality control samples. The extraction recovery of tamsulosin from plasma was in the range of 84.2-94.5%. The method has been used successfully to study tamsulosin pharmacokinetics in adult humans.

α1-Adrenergic receptor antagonists and gynecomastia. A case series from the Italian spontaneous reporting system and VigiBase(™).

PubMed

Viola, Ermelinda; Opri, Sibilla; Moretti, Ugo; Leone, Roberto; Casini, Maria Luisa; Ruggieri, Sara; Minore, Claudia; Conforti, Anita

2014-08-01

The aim of this study was to analyze the cases of gynecomastia associated with α1A-adrenergic receptor antagonists (α1-ARAs) in the Italian spontaneous reporting system database (Rete Nazionale di Farmacovigilanza or RNF) and in the World Health Organization ICSRs database (VigiBase(™)), focusing on tamsulosin use. We analyzed the spontaneous reports of gynecomastia related to the use of α1-ARAs and collected from the RNF and from VigiBase(™) up to December 2012. Cases of gynecomastia have been defined as reports associated with gynecomastia according with Medical Dictionary for Regulatory Activities (MedDRA). Reporting odds ratio (ROR) and Information Component (IC) were calculated as measures of disproportionality in RNF and VigiBase(™), respectively. Up to December 2012, about 186,000 reports were recorded in the RNF. Among these, 902 reports of adverse drug reaction (ADR) have been associated with the use of at least one α1-ARAs. Of these, in 15 cases, gynecomastia was a listed ADR: in 10, the suspected drug was tamsulosin (in eight, it was the sole suspect); in two, doxazosin and alfuzosin, respectively; and in one, terazosin. ROR for tamsulosin was 5.3 (95% CI 1.8, 15.7). In VigiBase(™), 84 reports of gynecomastia indicated tamsulosin as suspected drug. Tamsulosin-associated gynecomastia showed the highest IC value within this class of drugs (IC 95% 2.43). In this study, we highlight a possible association between gynecomastia and tamsulosin use. To our knowledge, this association has not been described before and could represent a potential signal.

Validated spectrofluorimetric method for the determination of tamsulosin in spiked human urine, pure and pharmaceutical preparations.

PubMed

Karasakal, A; Ulu, S T

2014-05-01

A novel, sensitive and selective spectrofluorimetric method was developed for the determination of tamsulosin in spiked human urine and pharmaceutical preparations. The proposed method is based on the reaction of tamsulosin with 1-dimethylaminonaphthalene-5-sulfonyl chloride in carbonate buffer pH 10.5 to yield a highly fluorescent derivative. The described method was validated and the analytical parameters of linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, recovery and robustness were evaluated. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over the range 1.22 × 10(-7) to 7.35 × 10(-6)  M. LOD and LOQ were calculated as 1.07 × 10(-7) and 3.23 × 10(-7)  M, respectively. The proposed method was successfully applied for the determination of tamsulosin in pharmaceutical preparations and the obtained results were in good agreement with those obtained using the reference method. Copyright © 2013 John Wiley & Sons, Ltd.

Comparing the efficacy of mydriatic cocktail-soaked sponge and conventional pupil dilation in patients using tamsulosin - a randomized controlled trial.

PubMed

Hargitai, János; Vezendi, László; Vigstrup, Jørgen; Eisgart, Finn; Lundbye-Christensen, Søren; Hargitai, Bálint; Vorum, Henrik

2013-12-20

A strong association exists between the use of tamsulosin and the occurance of intraoperative floppy iris syndrome. Several methods were advocated to overcome the progressive intraopertive miosis.Our purpose was to investigate the effect of a mydriatic-cocktail soaked cellulose sponge on perioperative pupil diameter in tamsulosin-treated patients undergoing elective cataract surgery. Patients using tamsulosin were dilated either with mydriatic-cocktail soaked sponge (group 1) or with conventional eyedrop regimen (group 2). Control patients not taking any α1 adrenergic receptor inhibtors were also dilated with mydriatic sponge (group 3).In all groups oxybuprocain 0.4%, cocain 4%, tropicamide 1%, phenylephrine 10%, diclophenac 0.1% along with chloramphenicol 0.5% were used preoperatively.Pupil diameter (mm) was measured preoperatively, after nucleus delivery, and before IOL implantation. Adverse effects associated with the use of sponge, minor and major intraoperative complications, the use of iris retractors and operation time were recorded.Differences in general between groups were analyzed with a one way analysis of variance (ANOVA); differences between groups in proportions were assessed by Fisher's exact test. Mean pupil diameter (mm) was preopertively: 7.52 ± 1.21, 7.30 ± 1.55 and 7.99 ± 0.96 (ANOVA: p = 0.079); after nucleus delivery: 6 ± 1.20, 6.29 ± 1.12 and 6.52 ± 0.81 (ANOVA: p = 0.123); before IOL implantation: 5.46 ± 1.06, 5.83 ± 1.09 and 6.17 ± 0.89 (ANOVA: p = 0.0291).No adverse effect related to sponge use was detected. Frequency of minor complications, and iris hook use was similar in the two tamsulosin treated group. Operation time did not differ significantly in the three groups. We have found that using a mydriatic cocktail-soaked wick - an alternative way to achieve intraoperative mydriasis for cataract surgery - was as effective and safe as the conventional repeated eyedrops regiment for tamsulosin treated patients. Current Controlled Trials ISRCTN37834752.

Measurement of tamsulosin in human serum by liquid chromatography-tandem mass spectrometry.

PubMed

Upreti, Rita; Homer, Natalie Z M; Naredo, Gregorio; Cobice, Diego F; Hughes, Katherine A; Stewart, Laurence H; Walker, Brian R; Andrew, Ruth

2013-07-01

A simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100μL) via liquid-liquid extraction with methyl tert-butyl ether (2mL) following dilution with 0.1M ammonium hydroxide (100μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis(®) Express C18 (100mm×3mm, 2.7μm) column using a gradient elution with mobile phases methanol and 2mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409→228 and d9-finasteride m/z 382→318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10ppm). The limit of quantitation was 0.2ng/mL, and the method was validated in the linear range 0.2-50ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

[Profile of silodosin].

PubMed

Montorsi, Francesco

2013-01-01

Silodosin is a highly selective alpha1A-adrenoceptor antagonist approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. Its clinical pharmacology profile offers a number of advantages, including uroselectivity, once-daily (QD) dosing, a standard dose of 8 mg QD that does not need to be adjusted according to age, and the feasibility of concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors and antihypertensive agents. Three phase 3 double-blind, randomised trials using the dosage regimen of 8 mg QD in > 800 patients have shown that silodosin is significantly more effective than placebo (p < 0.001) and at least as effective as tamsulosin (0.4 mg QD) in improving International Prostate Symptom Score (IPSS) total score, storage subscore, and voiding subscore. It is significantly more effective than tamsulosin in inducing simultaneous improvement of bothersome lower urinary tract symptoms such as incomplete emptying, frequency, and nocturia (p = 0.03). Safety data collected in 1581 patients exposed to chronic treatment with silodosin 8 mg QD have shown that the drug is safe and well tolerated. As was to be expected with a uroselective compound, cardiovascular effects have been minimal. The most common adverse reaction is "retrograde ejaculation" (anejaculation), which led to treatment discontinuation in only 3.9% of patients. The rare, drug class-related safety issue of intraocular floppy iris syndrome can be satisfactorily managed by warning patients simply to inform their ophthalmologist that they are or were on treatment with an alpha1-adrenoceptor blocker.

Comparing the efficacy of mydriatic cocktail-soaked sponge and conventional pupil dilation in patients using tamsulosin – a randomized controlled trial

PubMed Central

2013-01-01

Background A strong association exists between the use of tamsulosin and the occurance of intraoperative floppy iris syndrome. Several methods were advocated to overcome the progressive intraopertive miosis. Our purpose was to investigate the effect of a mydriatic-cocktail soaked cellulose sponge on perioperative pupil diameter in tamsulosin-treated patients undergoing elective cataract surgery. Methods Patients using tamsulosin were dilated either with mydriatic-cocktail soaked sponge (group 1) or with conventional eyedrop regimen (group 2). Control patients not taking any α1 adrenergic receptor inhibtors were also dilated with mydriatic sponge (group 3). In all groups oxybuprocain 0.4%, cocain 4%, tropicamide 1%, phenylephrine 10%, diclophenac 0.1% along with chloramphenicol 0.5% were used preoperatively. Pupil diameter (mm) was measured preoperatively, after nucleus delivery, and before IOL implantation. Adverse effects associated with the use of sponge, minor and major intraoperative complications, the use of iris retractors and operation time were recorded. Differences in general between groups were analyzed with a one way analysis of variance (ANOVA); differences between groups in proportions were assessed by Fisher’s exact test. Results Mean pupil diameter (mm) was preopertively: 7.52 ± 1.21, 7.30 ± 1.55 and 7.99 ± 0.96 (ANOVA: p = 0.079); after nucleus delivery: 6 ± 1.20, 6.29 ± 1.12 and 6.52 ± 0.81 (ANOVA: p = 0.123); before IOL implantation: 5.46 ± 1.06, 5.83 ± 1.09 and 6.17 ± 0.89 (ANOVA: p = 0.0291). No adverse effect related to sponge use was detected. Frequency of minor complications, and iris hook use was similar in the two tamsulosin treated group. Operation time did not differ significantly in the three groups. Conclusion We have found that using a mydriatic cocktail-soaked wick – an alternative way to achieve intraoperative mydriasis for cataract surgery – was as effective and safe as the conventional repeated eyedrops regiment for tamsulosin treated patients. Trial registration Current Controlled Trials ISRCTN37834752 PMID:24359572

Measurement of tamsulosin in human serum by liquid chromatography–tandem mass spectrometry☆

PubMed Central

Upreti, Rita; Homer, Natalie Z.M.; Naredo, Gregorio; Cobice, Diego F.; Hughes, Katherine A.; Stewart, Laurence H.; Walker, Brian R.; Andrew, Ruth

2013-01-01

A simple, sensitive and robust method to extract tamsulosin from human serum, and quantify by liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed and validated and is applicable as a measure of compliance in clinical research. Tamsulosin was extracted from human serum (100 μL) via liquid–liquid extraction with methyl tert-butyl ether (2 mL) following dilution with 0.1 M ammonium hydroxide (100 μL), achieving 99.9% analyte recovery. Internal standard, d9-finasteride, was synthesised in-house. Analyte and internal standard were separated on an Ascentis® Express C18 (100 mm × 3 mm, 2.7 μm) column using a gradient elution with mobile phases methanol and 2 mM aqueous ammonium acetate (5:95, v/v). Total run-time was 6 min. Tamsulosin was quantified using a triple quadrupole mass spectrometer operated in multi-reaction-monitoring (MRM) mode using positive electrospray ionisation. Mass transitions monitored for quantitation were: tamsulosin m/z 409 → 228 and d9-finasteride m/z 382 → 318, with the structural formulae of ions confirmed by Fourier transform ion cyclotron resonance mass spectrometry (within 10 ppm). The limit of quantitation was 0.2 ng/mL, and the method was validated in the linear range 0.2–50 ng/mL with acceptable inter- and intra-assay precision and accuracy and stability suitable for routine laboratory practice. The method was successfully applied to samples taken from research volunteers in a clinical study of benign prostatic hyperplasia. PMID:23743242

Silodosin: treatment of the signs and symptoms of benign prostatic hyperplasia.

PubMed

Curran, Monique P

2011-05-07

Silodosin is an α-adrenoceptor antagonist with high selectivity for α(1A)- relative to α(1B)- adrenoceptors. In men aged >50 years with benign prostatic hyperplasia (BPH), silodosin 8 mg once daily, compared with placebo, was associated with a significantly more rapid and effective improvement in the total International Prostate Symptom Score (IPSS) and the storage and voiding IPSS subscores in three 12-week, phase III trials conducted in Europe and the US. In the European trial, silodosin was at least as effective as tamsulosin 0.4 mg once daily in improving the total IPSS. Silodosin was significantly more effective than placebo (all three phase III trials) and tamsulosin (European phase III trial) in simultaneously improving nocturia, frequency and incomplete emptying, according to a post hoc analysis. Long-term, open-label extension trials demonstrated that silodosin provided sustained relief of the signs and symptoms of BPH for up to 1 year. Silodosin was generally well tolerated, and was associated with minimal cardiovascular adverse effects. Abnormal ejaculation, a class effect of α(1A)-adrenoceptor antagonists, was the most common silodosin-associated adverse reaction, but resulted in treatment withdrawal of only a limited number of patients. © 2011 Adis Data Information BV. All rights reserved.

Molecular cloning and functional expression of the guinea pig alpha(1a)-adrenoceptor.

PubMed

González-Espinosa, C; Romero-Avila, M T; Mora-Rodríguez, D M; González-Espinosa, D; García-Sáinz, J A

2001-08-31

In the present paper, the cloning and expression of the guinea pig alpha(1A)-adrenoceptor is presented. The nucleotide sequence had an open reading frame of 1401 bp that encoded a 466 amino-acid protein with an estimated molecular mass of approximately 51.5 kDa. When the clone was expressed in Cos-1 cells, specific high-affinity binding of [(3)H]prazosin and [(3)H]tamsulosin was observed. Chloroethylclonidine treatment of membranes slightly decreased the total binding with both radioligands. Binding competition experiments using [(3)H]tamsulosin showed the following potency order: (a) for agonists: oxymetazoline >epinephrine>norepinephrine>methoxamine, and (b) for antagonists: prazosin> or 5-methyl-urapidil=benoxathian>phentolamine>BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4,5]decane-7,9-dione). Photoaffinity labeling using [(125)I-aryl]azido-prazosin revealed a major broad band with a molecular mass between 70 and 80 kDa. The receptor was functional, as evidenced by an epinephrine-increased production of [(3)H]inositol phosphates that was blocked by prazosin.

The effects of tamsulosin and alfuzosin on iris morphology: an ultrasound biomicroscopic comparison.

PubMed

Aktas, Zeynep; Yuksel, Nilay; Ceylan, Gurhan; Polat, Fazli; Hasanreisoglu, Murat; Hasanreisoglu, Berati

2015-03-01

It is well known that Alpha-1 adrenergic receptor antagonists affect the receptors in the prostate and also iris dilator muscle, leading to loss of iris muscle tone. To compare morphological alterations of iris secondary to tamsulosin and alfuzosin use. Patients included in the study were grouped as follows: 16 patients treated with tamsulosin (Group 1), 14 patients treated with alfuzosin (Group 2) and 18 untreated controls (Group 3). All patients underwent ultrasound biomicroscopic and pupillometric examination. Iris thickness was measured at the dilator muscle region (DMR; measured at half of the distance between the scleral spur and the pupillary margin) and sphincter muscle region (SMR; Standardized at 0.75 mm from the pupillary margin). DMR/SMR was also calculated for each patient. Differences among groups were analysed. Main outcome measures were DMR, SMR, DMR/SMR and pupillary diameter. Mean duration of treatments were 2.4 ± 0.96 years (1-4) and 2.3 ± 1.01 years (1-4) in Groups 1 and 2. Pupillary diameters were reduced in Groups 1-2 compared to Group 3 (p < 0.001, p < 0.001). The SMR was similar in Groups 1 and 2 (p: 0.114). These values were not significantly different from that of Group 3 (p: 0.196, p: 0.209). However, thickness in the DMR in Groups 1-2 were significantly lower than that of controls (Group 3) whereas there was no significant difference between Groups 1 and 2 (p: 0.041, p: 0.039 and 0.986, respectively). Mean DMR/SMR ratios were significantly lower in Groups 1-2 than that of Group 3 (p: 0.040 and p: 0.040, respectively). In patients using these medications, the iris seems to be thinner at the dilator muscle region, but preserving the sphincter muscle region.

The efficacy of tamsulosin in lower ureteral calculi

PubMed Central

Griwan, M.S.; Singh, Santosh Kumar; Paul, Himanshu; Pawar, Devendra Singh; Verma, Manish

2010-01-01

Context: There has been a paradigm shift in the management of ureteral calculi in the last decade with the introduction of new less invasive methods, such as ureterorenoscopy and extracorporeal shock wave lithotripsy (ESWL). Aims: Recent studies have reported excellent results with medical expulsive therapy (MET) for distal ureteral calculi, both in terms of stone expulsion and control of ureteral colic pain. Settings and Design: We conducted a comparative study in between watchful waiting and MET with tamsulosin. Materials and Methods: We conducted a comparative study in between watchful waiting (Group I) and MET with tamsulosin (Group II) in 60 patients, with a follow up of 28 days. Statistical Analysis: Independent 't' test and chi-square test. Results: Group II showed a statistically significant advantage in terms of the stone expulsion rate. The mean number of episodes of pain, mean days to stone expulsion and mean amount of analgesic dosage used were statistically significantly lower in Group II (P value is 0.007, 0.01 and 0.007, respectively) as compared to Group I. Conclusions: It is concluded that MET should be considered for uncomplicated distal ureteral calculi before ureteroscopy or extracorporeal lithotripsy. Tamsulosin has been found to increase and hasten stone expulsion rates, decrease acute attacks by acting as a spasmolytic, reduces mean days to stone expulsion and decreases analgesic dose usage. PMID:20882156

Non-Adrenergic, Tamsulosin-Insensitive Smooth Muscle Contraction is Sufficient to Replace α1 -Adrenergic Tension in the Human Prostate.

PubMed

Hennenberg, Martin; Acevedo, Alice; Wiemer, Nicolas; Kan, Aysenur; Tamalunas, Alexander; Wang, Yiming; Yu, Qingfeng; Rutz, Beata; Ciotkowska, Anna; Herlemann, Annika; Strittmatter, Frank; Stief, Christian G; Gratzke, Christian

2017-05-01

Lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia may be caused by prostate smooth muscle contraction. Although α 1 -blockers may improve symptoms by prostate smooth muscle relaxation, their efficacy is limited. This may be explained by non-adrenergic mediators causing contraction in parallel to α 1 -adrenoceptors. However, little is known about the relevance and cooperative actions of non-adrenergic mediators in the prostate. Prostate tissues were obtained from radical prostatectomy (n = 127 patients). Contractile responses were studied in an organ bath. Endothelin-1 and noradrenaline induced contractions of similar magnitude (116 ± 23 and 117 ± 18% of KCl-induced contractions). Endothelin-2- and -3-induced maximum contractions of 63 ± 8.6 and 71 ± 19% of KCl, while contractions by the thromboxane analog U46619 amounted up to 63 ± 9.4%. Dopamine-induced contractions averaged to 22 ± 4.5% of KCl, while maximum contractions by serotonin, histamine, and carbachol stayed below 10% of KCl-induced. While noradrenaline-induced contractions were inhibited by tamsulosin (300 nM), endothelin-1-, -2-, or -3-induced contraction were not. No additive effects were observed if endothelins and noradrenaline were applied consecutively to the same samples. If endothelin-1 was applied after U46619, resulting tension (172 ± 43% of KCl) significantly exceeded noradrenaline-induced contraction. Tensions following combined application of endothelin-2 or -3 with U46619 stayed below noradrenaline-induced contractions. Tension following combined application of all three endothelins with U46619 resembled maximum noradrenaline-induced tone. Contractions following concomitant confrontation of human prostate tissue with noradrenaline and endothelin-1 are not additive. Endothelin-1 is sufficient to induce a smooth muscle tone resembling that of noradrenaline. This may replace lacking α 1 -adrenergic tone under therapy with α 1 -blockers, explaining the limited efficacy of α 1 -blockers in LUTS treatment. Contractions by thromboxane and endothelin-1 may be additive, and may exceed α 1 -adrenergic tone. Prostate 77:697-707, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Efficacy of phosphodiesterase type 5 inhibitors for the treatment of distal ureteral calculi: A systematic review and meta-analysis

PubMed Central

García-Perdomo, Herney Andrés

2017-01-01

Purpose To determine the efficacy of phosphodiesterase type 5 inhibitors (PDE5i) as medical expulsive therapy (MET) for the treatment of distal ureteral calculi. Materials and Methods A search strategy was conducted in the MEDLINE, CENTRAL, and Embase databases. Searches were also conducted in other databases and unpublished literature. Clinical trials were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. An analysis of random effects due to statistical heterogeneity was conducted. The primary outcome was the expulsion rate of the distal ureteral calculus in 28 days. The secondary outcomes were the time to expulsion, side effects of treatment, and amount (mg) of nonopioid analgesia. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were PDE5i vs. placebo, tadalafil vs. placebo, and tadalafil vs. tamsulosin. Results Four articles were included in the qualitative and quantitative analysis. Records of 580 patients were found among the four studies. A low risk of bias was shown for the majority of the study items. The calculi expulsion rate had an RD of 0.26 (95% CI, 0.15–0.37) and a less prolonged expulsion as a secondary outcome with a mean difference of -4.39 days (95% CI, -6.69 to -2.09) in favor of PDE5i compared with the placebo. No significant difference was found for these outcomes when comparing tadalafil with tamsulosin. Conclusions Compared with a placebo, PDE5i could be effective as MET for the treatment of distal ureter calculi. PMID:28261676

Polymorphism in R-tamsulosin (an alpha blocker): The unexpected manifestation of a sulfonamide⋯o-diethoxybenzene heterosynthon

NASA Astrophysics Data System (ADS)

Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, Krishnan

2014-12-01

A two point Nsbnd H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P21, C2, and P21 space groups respectively with two molecules in the asymmetric unit (Z‧ = 2), whereas, form III of freebase crystallize in the orthorhombic P212121 space group with Z‧ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯o-diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring sulfonamide homo and heterosynthons.

The influence of Surelease and sodium alginate on the in-vitro release of tamsulosin hydrochloride in pellet dosage form.

PubMed

Kim, Min-Soo; Jun, Seoung Wook; Lee, Sibeum; Lee, Tae Wan; Park, Jeong-Sook; Hwang, Sung-Joo

2005-06-01

The objective of this study was to prepare controlled-release pellets containing 0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers with Surelease and sodium alginate. The release of tamsulosin HCl from pellets coated with the commercial aqueous ethylcellulose dispersion (Surelease) was investigated at different coating loads. In addition, the effect of sodium alginate on drug release was investigated by varying the ratio of sodium alginate to microcrystalline cellulose (MCC). Dissolution studies were first performed in 500 mL simulated gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross sections were examined by scanning electron microscopy (SEM). Apparently, the spherical pellets were prepared using a pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from Surelease-coated pellets were significantly affected by changing the content of Surelease, the pH of the dissolution medium and the ratio of sodium alginate to MCC. The drug release rates not only decreased with increase in the coating load, but also increased when the pH of the dissolution medium was increased from 1.2 to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results suggest that Surelease and sodium alginate would be useful excipients in the preparation of controlled-release pellets with the desired release profiles.

Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH – a double-blind randomized trial

PubMed Central

Manohar, Chikka Moga Siddaiah; Nagabhushana, Mahadevappa; Sanjay, Ramachandra Pudakalkatti; Kamath, Ananth Janardhan; Keshavamurthy, Ramaiah

2017-01-01

Introduction Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Material and methods Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). Results IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p <0.001) and 12 (1.2 ±0.66, p <0.001) weeks in Group S. The mean Qmax improvement was the maximum (13.76 ±2.44, p = 0.028) in Group S at 1 week. Reduction in PVR was the maximum in Group S, but it was not statistically significant. Adverse drug events (ADE) were observed in 20.07% (54/269) patients and distribution was similar in the three groups with decreasing incidence with progression of time. Conclusions Silodosin is the most efficacious AB with rapid onset of action. Silodosin also improves the quality of life in patients with LUTS due to BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin. PMID:28721281

Safety and efficacy of tamsulosin, alfuzosin or silodosin as monotherapy for LUTS in BPH - a double-blind randomized trial.

PubMed

Manohar, Chikka Moga Siddaiah; Nagabhushana, Mahadevappa; Karthikeyan, Vilvapathy Senguttuvan; Sanjay, Ramachandra Pudakalkatti; Kamath, Ananth Janardhan; Keshavamurthy, Ramaiah

2017-06-30

Currently alpha1-adrenoceptor blockers (AB) are widely used as first-line therapy to improve lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). We compared the efficacy and safety profile of tamsulosin, alfuzosin and silodosin in LUTS due to BPH. Consecutive consenting male patients (N = 269) undergoing medical management of BPH with AB from February 2012 to October 2015 were enrolled. Patients were randomized to a 0.4 mg tamsulosin (group T), 10 mg alfuzosin (group A) or a 8 mg silodosin (group S) by double-blind randomization. All patients were assessed for improvements and post-void residual urine (PVR) and for adverse drug events (ADE). IPSS showed significant improvement in Group S at the first week (11.7 ±4.18, p = 0.027) and at 3 months (7.97 ±3.84, p = 0.020). QOL showed significant improvement at 1 (2.2 ±0.76, p = 0.020), 4 (1.47 ±0.63, p <0.001) and 12 (1.2 ±0.66, p <0.001) weeks in Group S. The mean Qmax improvement was the maximum (13.76 ±2.44, p = 0.028) in Group S at 1 week. Reduction in PVR was the maximum in Group S, but it was not statistically significant. Adverse drug events (ADE) were observed in 20.07% (54/269) patients and distribution was similar in the three groups with decreasing incidence with progression of time. Silodosin is the most efficacious AB with rapid onset of action. Silodosin also improves the quality of life in patients with LUTS due to BPH and objectively improves maximum flow rate. However, silodosin has more adverse events when compared to tamsulosin and alfuzosin.

Benign prostatic hyperplasia and lower urinary tract symptoms. A review of current evidence.

PubMed

Carrero-López, V M; Cózar-Olmo, J M; Miñana-López, B

2016-06-01

The treatment of benign prostatic hyperplasia (BPH) is changing due to a greater understanding of the disease and the development of the functional concept of lower urinary tract symptoms (LUTS). To describe the current state of BPH and the diagnosis and treatment of LUTS. We summarise the issues presented and debated by a group of expert urologists during the First UROVI Congress, sponsored by the Spanish Urological Association. LUTS encompasses filling, voiding and postvoiding symptoms that affect patients' quality of life. The aetiological diagnosis is an important element in starting the most ideal treatment. For this reason, new alternative therapies (both pharmacological and surgical) are needed to help individually address the symptoms in the various patient profiles. There is now a new combination of drugs (6mg of solifenacin and 0.4mg of the tamsulosin oral controlled absorption system) for treating moderate to severe filling symptoms and emptying symptoms associated with BPH in patients who do not respond to monotherapy. Furthermore, new surgical techniques that are increasingly less invasive help provide surgical options for older patients and those with high comorbidity. The availability of drugs that can act on the various LUTS helps integrate the pathophysiological paradigm into the functional one, providing more appropriate treatment for our patients. Copyright © 2016. Publicado por Elsevier España, S.L.U.

Sexual function in hypertensive patients receiving treatment.

PubMed

Reffelmann, Thorsten; Kloner, Robert A

2006-01-01

In many forms of erectile dysfunction (ED), cardiovascular risk factors, in particular arterial hypertension, seem to be extremely common. While causes for ED are related to a broad spectrum of diseases, a generalized vascular process seems to be the underlying mechanism in many patients, which in a large portion of clinical cases involves endothelial dysfunction, ie, inadequate vasodilation in response to endothelium-dependent stimuli, both in the systemic vasculature and the penile arteries. Due to this close association of cardiovascular disease and ED, patients with ED should be evaluated as to whether they may suffer from cardiovascular risk factors including hypertension, cardiovascular disease or silent myocardial ischemia. On the other hand, cardiovascular patients, seeking treatment of ED, must be evaluated in order to decide whether treatment of ED or sexual activity can be recommended without significantly increased cardiac risk. The guideline from the first and second Princeton Consensus Conference may be applied in this context. While consequent treatment of cardiovascular risk factors should be accomplished in these patients, many antihypertensive drugs may worsen sexual function as a drug specific side-effect. Importantly, effective treatment for arterial hypertension should not be discontinued as hypertension itself may contribute to altered sexual functioning; to the contrary, alternative antihypertensive regimes should be administered with individually tailored drug regimes with minimal side-effects on sexual function. When phosphodiesterase-5 inhibitors, such as sildenafil, tadalafil and vardenafil, are prescribed to hypertensive patients on antihypertensive drugs, these combinations of antihypertensive drugs and phosphodiesterase 5 are usually well tolerated, provided there is a baseline blood pressure of at least 90/60 mmHg. However, there are two exceptions: nitric oxide donors and alpha-adrenoceptor blockers. Any drug serving as a nitric oxide donor (nitrates) is absolutely contraindicated in combination with phosphodiesterase 5 inhibitors, due to significant, potentially life threatening hypotension. Also, a-adrenoceptor blockers, such as doxazosin, terazosin and tamsulosin, should only be combined with phosphodiesterase 5 inhibitors with special caution and close monitoring of blood pressure.

Open-label, 9-month extension study investigating the uro-selective alpha-blocker silodosin in men with LUTS associated with BPH.

PubMed

Osman, Nadir I; Chapple, Christopher R; Tammela, Teuvo L; Eisenhardt, Andreas; Oelke, Matthias

2015-05-01

To evaluate the long-term safety (primary objective) and efficacy/impact on quality of life (QoL, secondary objectives) of silodosin 8 mg once daily in men with LUTS/BPH. Men who completed the 12-week double-blind study with silodosin 8 mg, tamsulosin 0.4 mg, or placebo were offered to continue with the 9-month open-label study during which all patients received silodosin 8 mg once daily. Safety was assessed by analysing vital signs, electrocardiograms, laboratory tests, and adverse events. Efficacy was evaluated with the International Prostate Symptom Score (IPSS), IPSS voiding and storage sub-scores, IPSS-QoL, and maximum urinary flow rate (Q max). A total of 500 patients (mean age 66 years) entered the 9-month open-label study. Treatment-emergent adverse events (TEAE) were experienced by 33.4% patients. Ejaculation dysfunction was the most common TEAE (9.0%) but led to study discontinuations in only 1.6% of patients. Dizziness without orthostatic hypotension occurred in 0.8%. A marked reduction in total IPSS (-2.7 ± 3.8) was documented at the first visit of this extension phase in patients having de novo silodosin compared with lesser improvement in patients previously treated with silodosin (-0.82 ± 4.2) or tamsulosin (-0.83 ± 3.8). Improvements were maintained throughout the open-label phase. QoL also improved, with the greatest improvement in de novo silodosin patients. No relevant changes in Q max occurred. Long-term treatment with silodosin was safe and efficacious. Abnormal ejaculation was the most common TEAE, but led to treatment discontinuation in only 1.6% of patients. Orthostatic hypotension was not seen, and only a few patients experienced dizziness.

[Ejaculatory disorders except premature ejaculation, orgasmic disorders].

PubMed

Rigot, J-M; Marcelli, F; Giuliano, F

2013-07-01

Disorders of ejaculation and orgasm apart from premature ejaculation are pretty uncommon. Medical literature was reviewed and combined with expert opinion of the authors. The semiology of these disorders is essential: aspermia, hypospermia, retrograde ejaculation, delayed or absent ejaculation with or without orgasm. Whether this is a lifelong or acquired condition, it is essential to assess the side-effects of medications i.e. psychotropic drugs, including antidepressant, neuroleptics, tramadol, alphablockers: tamsulosin and silodosin must always be surveyed. The management is often difficult, especially with a parenthood perspective. The management of lifelong disorders must rely on psychosexual therapies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

[Intraoperative floppy iris syndrome after treatment with duloxetine: coincidence, association, or causality?].

PubMed

González-Martín-Moro, J; González-López, J J; Zarallo-Gallardo, J; Fernández-Miguel, Y

2015-02-01

The case is presented of a severe Intraoperative Floppy Iris Syndrome (IFIS) in a patient that had been treated with duloxetine. Tamsulosin is the main etiological agent involved in IFIS. However several cases of IFIS, supposedly secondary to drugs of different groups have recently been reported in the literature. The authors use this case report as a means to discuss why most of these cases should be considered anecdotal evidence. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Multichannel impedance monitoring for evaluation of alpha-adrenoblocker effect on the ureteral function in patients with stone disease

NASA Astrophysics Data System (ADS)

Apolikhin, O. I.; Khodyreva, L. A.; Mudraya, I. S.; Kirpatovsky, V. I.; Serdyuk, A. A.

2010-04-01

The study of distal ureter function was carried out on patients with stones in the upper urinary tract, who underwent ureteroscopy and lithotripsy procedures. The parameters of ureteral peristalsis such as peristalsis amplitude, peristalsis rate, ureteral wall tone, contractile wave duration, and its direction obtained by multichannel impedance ureterography were assessed and compared from two groups of patients. The group I patients received tamsulosin in addition to standard regimen, while the group II patients matched according to the stone size and location were managed without tamsulosin medical therapy. In comparison with group II, the group I patients demonstrated smaller average peristalsis amplitude (0.60±0.08 vs 0.81±0.06 Ohm), shorter contractions (7.1±0.3 vs 7.7±0.3 s), greater peristalsis rate (3.3±0.3 vs 2.8±0.2 per minute), and diminished ureteral tone (4.0±0.5 vs 4.7±0.2 Ohm-1). Incidence of the retrograde contractile waves was two-fold greater in the group II, while normal antegrade regular contractions were 30% more frequent in the group I. In addition, our results showed that the effect of tamsulosin on ureteral function was manifested in the patients with different stone size and location in the upper urinary tract, and it depended pronouncedly on individual ureteral tone and contractility parameters.

Efficacy of α-Adrenergic Receptor Blockers in the Treatment of Male Lower Urinary Tract Symptoms

PubMed Central

Roehrborn, Claus G

2009-01-01

Male lower urinary tract symptoms (LUTS) are one of the most common causes for a consultation with a health care provider, and one of the most common causes of male LUTS is benign prostatic hyperplasia (BPH). In recent decades, medical therapy has established itself as viable and cost effective for the majority of men. For the treatment of male LUTS in the United States, the 5 currently available α-adrenergic receptor blockers are alfuzosin, doxazosin, silodosin, terazosin, and tamsulosin. α-Blockers remain one of the mainstays in the treatment of male LUTS and clinical BPH. They exhibit an early onset of efficacy (within less than 1 week) with regard to both symptoms and flow rate improvement, maintain such improvements in open-label and controlled trials for up to 5 years, and have been shown to prevent symptomatic progression. PMID:20126606

Prostate cell membrane chromatography-liquid chromatography-mass spectrometry for screening of active constituents from Uncaria rhynchophylla.

PubMed

He, Jianyu; Han, Shengli; Yang, Fangfang; Zhou, Nan; Wang, Sicen

2013-01-01

Uncaria rhynchophylla is a traditional Chinese medicinal herb used to treat hypertension and convulsive disorders such as epilepsy. Rat prostate cell membrane chromatography combined with liquid chromatography-mass spectrometry (LC-MS) was used to identify active constituents from U. rhynchophylla extracts. Four compounds (corynoxeine, isorhynchophylline, isocorynoxeine and rhynchophylline) were discovered. Competitive binding assay results indicated that the four compounds were in direct competition at a single common binding site and interacted with α1A adrenergic receptors (α1A-AR) in a manner similar to tamsulosin. Affinity constant values of the four compounds binding with α1A-AR were also measured using rat prostate cell membrane chromatography (CMC). Finally, their pharmacodynamic effects were tested on rat caudal arteries. This CMC combined LC-MS system offers a means of drug discovery by screening natural medicinal herbs for new pharmacologically active molecules targeting specific receptors.

Effects of specific alpha-1A/1D blocker on lower urinary tract symptoms due to double-J stent: a prospectively randomized study.

PubMed

Wang, Chung-Jing; Huang, Shi-Wei; Chang, Chien-Hsing

2009-06-01

The aim of our study was to evaluate the effect of tamsulosin in improving symptoms in patients with indwelling double-J ureteral stents. This prospective study lasted from April 2006 to March 2008. All the patients with symptomatic lower ureteral stones with <15 mm diameter were enrolled, and were prospectively randomized (random numbers table) into two groups. A total of 154 patients, with insertion of a double-J ureteral stent after ureteroscopic stone removal. In group 1, 75 patients were enrolled and received placebo for 2 weeks. Group 2 included 79 patients who received 0.4 mg of tamsulosin, once daily for 2 weeks. All patients completed the validated ureteral stent symptom questionnaire (USSQ) and quality of life of international prostate symptom scale (IPSS) for evaluating the symptoms of double-J stents and quality of life after double-J stent insertion and removal, respectively. The analysis of the questionnaire at W1 revealed a significant difference in the main score index of urinary symptoms, body pain and general health between groups 1 and 2. When comparing W1 evaluation with that of W4 after double-J removal, both groups showed significant worsening of urinary symptoms, body pain, general health and work performance, except sexual performance. The mean score of quality of life in IPSS was 4.21 in group 1 and 1.6 in group 2. Tamsulosin can improve a subset of stent-related urinary symptoms and quality of life effectively and may be applied in routine clinical practice.

Analgesic and anti-inflammatory effects of honey: the involvement of autonomic receptors.

PubMed

Owoyele, Bamidele Victor; Oladejo, Rasheed Olajiire; Ajomale, Kayode; Ahmed, Rasheedat Omotayo; Mustapha, Abdulrasheed

2014-03-01

The use of honey for therapeutic purposes is on the increase and many studies have shown that honey has the ability to influence biological systems including pain transmission. Therefore, this study was designed to investigate the analgesic and anti-inflammatory effects of honey and the effects of concurrent administration of autonomic nervous system blocking drugs. Studies on analgesic activities was carried out using hotplate and formalin-induced paw licking models while the anti-inflammatory activity was by the carrageenan paw oedema method. Animals were distributed into six groups consisting of five animals each. They were administered saline, honey (600 mg/kg), indomethacin (5 mg/kg), autonomic blockers (3 μg/kg of tamsulosin, 20 mg/kg (intraperitoneally) of propranolol, 2 ml/kg of atropine or 10 mg/kg (intra muscularly) of hexamethonium) or honey (200 and 600 mg/kg) with one of the blockers. The results showed that honey reduced pain perception especially inflammatory pain and the administration of tamsulosin and propranolol spared the effect of honey. Hexamethonium also spared the effects of honey at the early and late phases of the test while atropine only inhibited the early phase of the test. However, atropine and hexamethonium spared the anti-inflammatory effects of honey but tamsulosin abolished the effects while propranolol only abolished the anti-inflammatory effects at the peak of the inflammation. The results suggest the involvement of autonomic receptors in the anti-nociceptive and anti-inflammatory effects of honey although the level of involvement depends on the different types of the receptors.

Effect of alpha(1)-acid glycoprotein on the pharmacokinetics of tamsulosin in rats treated with turpentine oil.

PubMed

Matsushima, H; Watanabe, T; Higuchi, S

2000-04-01

The pharmacokinetics of tamsulosin (TAM) was investigated using male Sprague-Dawley rats in which plasma alpha(1)-acid glycoprotein (alpha(1)-AGP) levels were elevated by the subcutaneous injection of 0.2 mL/kg of turpentine oil. alpha(1)-AGP levels increased about eight times after turpentine oil treatment, causing a threefold decrease in plasma unbound fraction (f(u)) of TAM. When 0.3 mg/kg of TAM was dosed intravenously, total and nonrenal clearances (CL(tot) and CL(nr)) in turpentine-treated rats were 47% and 44% lower than those in nontreated controls, respectively. The area under the concentration-time curve of plasma unbound TAM (AUC(inf,u)) was lower than that in the control. When 1 mg/kg of TAM was dosed orally, oral clearance (CL(oral)) in alpha1-AGP-induced rats was 65% lower than in the control. The AUC(inf,u) and unbound oral clearance (CL(oral,u)) were nearly equal in both groups. Moreover, a positive correlation was observed between fu and CL(oral) of TAM (r(2) = 0.603, P < 0.01), whereas no correlation was observed between f(u) and CL(oral,u). The absolute bioavailability (BA) increased from 19.2% to 46.9% by induction of alpha(1)-AGP. These results suggest that decreased f(u) caused by the elevation of plasma alpha(1)-AGP level affects the pharmacokinetics of TAM, but does not affect the CL(oral,u,) which represents the hepatic metabolism of TAM. Copyright 2000 Wiley-Liss, Inc.

Discovery of ONO-7300243 from a Novel Class of Lysophosphatidic Acid Receptor 1 Antagonists: From Hit to Lead

PubMed Central

2016-01-01

Lysophosphatidic acid (LPA) evokes various physiological responses through a series of G protein-coupled receptors known as LPA1–6. A high throughput screen against LPA1 gave compound 7a as a hit. The subsequent optimization of 7a led to ONO-7300243 (17a) as a novel, potent LPA1 antagonist, which showed good efficacy in vivo. The oral dosing of 17a at 30 mg/kg led to reduced intraurethral pressure in rats. Notably, this compound was equal in potency to the α1 adrenoceptor antagonist tamsulosin, which is used in clinical practice to treat dysuria with benign prostatic hyperplasia (BPH). In contrast to tamsulosin, compound 17a had no impact on the mean blood pressure at this dose. These results suggest that LPA1 antagonists could be used to treat BPH without affecting the blood pressure. Herein, we report the hit-to-lead optimization of a unique series of LPA1 antagonists and their in vivo efficacy. PMID:27774128

Medication Effects on Periurethral Sensation and Urethral Sphincter Activity

PubMed Central

Greer, W. Jerod; Gleason, Jonathan L.; Kenton, Kimberly; Szychowski, Jeff M.; Goode, Patricia S; Richter, Holly E

2014-01-01

Aim To characterize urethral neuromuscular function before and 2 weeks after medication therapy. Methods Premenopausal women without lower urinary tract symptoms were randomly allocated to one of six medications for 2 weeks (pseudoephedrine ER 120mg, imipramine 25mg, cyclobenzaprine 10mg, tamsulosin 0.4mg, solifenacin 5mg or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle EMG (CNE) of the urethral sphincter using automated Multi-Motor Unit Action Potential (MUP) software; current perception threshold (CPT) testing to measure periurethral sensation; and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. Results 56 women had baseline testing; 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean 34.3 ± 10.1), BMI (mean 31.8 ± 7.5), parity (median 1, range 0–7), or race (14% Caucasian, 80% African American). PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5 Hz stimulation level, was observed following treatment with pseudoephedrine (0.15 to 0.09 mA at 5Hz; P=0.03). Conclusion In women without LUTS, pseudoephedrine improved urethral sensation, but not urethral neuromuscular function on CNE or pressure flow studies. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function. PMID:25185603

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia.

PubMed

Kawahara, Takashi; Morita, Satoshi; Ito, Hiroki; Terao, Hideyuki; Sakata, Ryoko; Ishiguro, Hitoshi; Tanaka, Katsuyuki; Miyamoto, Hiroshi; Matsuzaki, Junichi; Kubota, Yoshinobu; Uemura, Hiroji

2013-06-12

Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH.

Minimal Rectal Toxicity in the Setting of Comorbid Crohn's Disease Following Prostate Cancer Radiotherapy with a Hydrogel Rectal Spacer.

PubMed

Singh, Raj; Jackson, Philip S; Blake, Mollie; Cutlip, James; Sharma, Sanjeev

2017-08-01

We present one of the first cases of a prostate cancer (PCa) patient with inflammatory bowel disease (IBD) treated with intensity-modulated radiotherapy (IMRT) and a hydrogel rectal spacer. A 73-year-old male with a past medical history significant for Crohn's disease (CD) and the recent diagnosis of T1cN0M0 high-risk PCa was referred for definitive radiotherapy. Given the patient's history of CD and the possible increased risk of gastrointestinal (GI) toxicity and disease exacerbation, prior to IMRT, a hydrogel spacer was placed between the prostate and the anterior rectal wall to further minimize irradiation to the rectum. The patient then received IMRT (78 Gy/2 Gy fractions at a 100 percent isodose line). Over the course of treatment, Radiation Therapy Oncology Group (RTOG) Grade 1 GI toxicities of mild diarrhea were noted during the fifth and sixth weeks of treatment as well as an RTOG Grade 1 genitourinary (GU) toxicity of a decrease in the urinary stream that resolved with tamsulosin. At the 3, 6, 9, and 12-month follow-ups, bowel movements and urinary stream were reported to be at baseline with prostate-specific antigen (PSA) levels of 0.18 ng/mL and 0.03 ng/mL at the three and nine-month follow-ups, respectively. As such, this case report suggests that IBD patients with localized PCa may be viable candidates for radiotherapy given the promising results of hydrogel spacers in combination with IMRT in limiting rectal toxicity.

Silodosin in the management of lower urinary tract symptoms as a result of benign prostatic hyperplasia: who are the best candidates.

PubMed

Capitanio, U; Salonia, A; Briganti, A; Montorsi, F

2013-06-01

As the clinical effects of the available α1-adrenoceptors (ARs) blockers are usually considered comparable for treatment in patients suffering from lower urinary tract symptoms (LUTS) secondary to prostatic enlargement, officially recognised guidelines do not make specific recommendations regarding the choice of which agent should be considered according to the patient's characteristics. To analyse data supporting the use of silodosin, a highly selective once-daily dosing α1-ARs blocker, in different daily clinical practice scenarios. A structured literature review was performed using data retrieved from articles assessing the role of silodosin in the management of LUTS secondary to benign prostatic hyperplasia (BPH). A literature search of English language publications was performed using MEDLINE(®) and Web of Science from 2000 to 2012 using the terms LUTS; BPH; silodosin; α1-ARs blockers. The papers with the highest level of evidence were identified and represent the basis of the present review. Available data coming from basic research analyses, randomised trials and prospective studies showed that silodosin is efficacious for the initial management of patients with LUTS. Clinical developmental safety data from patients receiving silodosin with concomitant antihypertensive therapy do not indicate an increase in risk of orthostatic hypotension. In this context, a recent study demonstrated that silodosin can be safely administered to patients who are consensually assuming phosphodiesterase type 5 inhibitors. A recent randomised crossover study comparing the efficacy of silodosin and tamsulosin in patients with LUTS showed that further significant improvement was observed after switching to silodosin treatment, while worsening or little improvement was observed after switching to tamsulosin treatment. Preliminary results seem to demonstrate a potential role of silodosin in the treatment of chronic prostatitis/chronic pelvic pain syndrome and to facilitate ureteral stone passage, as well. When considering the above cited pharmacological and clinical characteristics of the drug, silodosin can be considered in the following clinical scenario: patients suffering from moderate-severe nocturia, patients with low normal blood pressure levels and patients concomitantly treated with antihypertensive medications, patients concomitantly treated with phosphodiesterase type 5 inhibitors, patients not satisfied (for efficacy or tolerability) with previous treatment with other α1-ARs blockers. Silodosin is efficacious for the initial management of patients with LUTS. Silodosin has a good cardiovascular safety profile and can be considered an option in patients with cardiovascular co-morbidities. It seems to be especially beneficial in patients with nocturia alone or presenting with the symptomatic trial nocturia-frequency-incomplete emptying. Patients on phosphodiesterase type 5 inhibitors treatment can be safely managed with silodosin. © 2013 John Wiley & Sons Ltd.

Ramelteon combined with an α1-blocker decreases nocturia in men with benign prostatic hyperplasia

PubMed Central

2013-01-01

Background Nocturia is defined as waking one or more times during the night due to the urge to void. Recently, the effectiveness of several sedatives and analgesics for nocturia has been reported. We herein investigated the effects of ramelteon, an antioxidant and sleep inducer, on nocturia unresponsive to α1-blocker monotherapy in males with lower urinary tract symptoms (LUTS) as a pilot study. Methods Subjects were 19 patients who had LUTS suggestive of benign prostate hyperplasia, received α1-blockers (tamsulosin, silodosin, or naftopidil), and continued to have two or more episodes of nocturia per night before starting ramelteon. Ramelteon at 8 mg once daily for one month was added to the α1-blocker. A self-administered questionnaire including the International Prostate Symptom Score (IPSS), quality of life (QoL) index, Overactive Bladder Symptom Score (OABSS), and Nocturia Quality-of-Life Questionnaire (N-QOL) were assessed before and one month after starting ramelteon. Results The mean score on IPSS question 7 (nocturia) decreased significantly from 2.88 before starting ramelteon to 2.41 one month after starting the medication (P = 0.03). The mean total OABSS decreased significantly from 6.31 to 5.38 (P = 0.03), and the mean for OABSS question 2 (nighttime frequency of nocturia) also significantly decreased from 2.63 to 2.13 (P = 0.01). The mean total N-QOL score did not change significantly. Two patients had dizziness; the remaining patients had no adverse drug-related events. Conclusions Ramelteon in combination with an α1-blocker could be a treatment option for reducing nocturia in men with BPH. PMID:23758651

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon® ) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): Systematic review and meta-analysis of randomized controlled trials and observational studies.

PubMed

Vela-Navarrete, Remigio; Alcaraz, Antonio; Rodríguez-Antolín, Alfredo; Miñana López, Bernardino; Fernández-Gómez, Jesús M; Angulo, Javier C; Castro Díaz, David; Romero-Otero, Javier; Brenes, Francisco J; Carballido, Joaquín; Molero García, José M; Fernández-Pro Ledesma, Antonio; Cózar Olmos, José Manuel; Manasanch Dalmau, José; Subirana Cachinero, Isaac; Herdman, Michael; Ficarra, Vincenzo

2018-04-25

To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon), at a dose of 320 mg daily, as monotherapy for the treatment of LUTS/BPH. Systematic review and meta-analysis of randomized and observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge [ISI], Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data was collected on IPSS score, peak urinary flow (Qmax), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADR). Data obtained from randomized controlled trials (RCT) and observational studies (OS) were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies which included patients on longer-term treatment (≥one year). Data from 27 studies (15 RCTs and 12 OS) were included for meta-analysis (total N=5,800). Compared with placebo, the HESr was associated with 0.64 (95% CI -0.98 to -0.31) fewer voids per night (p=0.0001) and an additional mean increase in Qmax of 2.75 mL/s (95% CI 0.57 to 4.93; p=0.01). When compared with alpha-blockers, the HESr showed similar improvements on IPSS (WMD 0.57; 95%CI, -0.27 to 1.42; p=0.18) and a comparable increase in Qmax to tamsulosin (WMD -0.02; 95%CI, -0.71 to 0.66; p=0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5ARIs. Analysis of all available published data for the HESr showed a mean improvement in IPSS score from baseline of -5.73 points (95% CI -6.91 to -4.54; p<0.0001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on PSA. Prostate volume decreased slightly. Similar efficacy results were observed in patients treated for ≥1 year (n=447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). The present meta-analysis, which includes all available RCTs and OS, shows that the HESr (Permixon) reduced nocturia and improved Qmax compared with placebo and had a similar efficacy to tamsulosin and short-term 5-ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the long-term medical treatment of LUTS/BPH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Systematic Review of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome

PubMed Central

Qin, Zongshi; Wu, Jiani; Zhou, Jing; Liu, Zhishun

2016-01-01

Abstract Acupuncture is a promising therapy for relieving symptoms in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), which affects >15% of adult men worldwide. The aim of the study was to assess the effects and safety of the use of acupuncture for CP/CPPS. MEDLINE, EMBASE, CENTRAL, Web of Science, CBM, CNKI, Wang-Fang Database, JCRM, and CiNii were searched from their inception through 30 November 2015. Grey literature databases and websites were also searched. No language limits were applied. Only randomized controlled trials (RCTs) with CP/CPPS treated by acupuncture were included. Two reviewers extracted data and assessed the risk of bias of RCTs using the Cochrane Risk of Bias Tools, respectively. Seven trials were included, involving 471 participants. The result of meta-analysis indicated that compared with sham acupuncture (MD: −6.09 [95%CI: −8.12 to −5.68]) and medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) (MD: −4.57 [95%CI: −7.58 to −1.56]), acupuncture was more effective at decreasing the total NIH-CPSI score. Real acupuncture was superior to sham acupuncture in improving symptoms (pain, voiding) and quality of life (Qof) domain subscores. Compared to sham acupuncture and medicine, acupuncture appears to be more effective at improving the global assessment. Two trials found that there is no significant difference between acupuncture and sham acupuncture in decreasing the IPSS score. Acupuncture failed to show more favorable effects in improving both symptoms and the Qof domain compared with medicine. Overall, current evidence supports acupuncture as an effective treatment for CP/CPPS-induced symptoms, particularly in relieving pain. Based on the meta-analysis, acupuncture is superior to sham acupuncture in improving symptoms and Qof. Acupuncture might be similar to medicine (Levofloxacinand, Ibuprofen, and Tamsulosin) in its long-term effects, but evidence was limited due to high ROB among included trials as well as potential heterogeneity. Acupuncture is associated with rare and slightly adverse events. Protocol registration PROSPERO CRD42015027522. PMID:26986148

77 FR 7167 - National Institute of Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... Diabetes and Digestive and Kidney Diseases; Notice of Closed Meetings Pursuant to section 10(d) of the... Diabetes and Digestive and Kidney Diseases Special Emphasis Panel Multi-Center Study of Tamsulosin for Ureteral Stones in the Emergency Department. Date: March 26, 2012. Time: 11 a.m. to 12 p.m. Agenda: To...

Saw palmetto and benign prostatic hyperplasia.

PubMed

Gong, Edward M; Gerber, Glenn S

2004-01-01

Benign prostatic hyperplasia (BPH) is a common health issue that affects 8% of all men at the age of 40, 60% of men in their 70s, and 90% of those greater than 80 years of age. One-fourth of these men will develop moderate to severe lower urinary tract symptoms that greatly affect their quality of life. Recent evidence suggests that the use of saw palmetto leads to improvements in urinary function for those suffering from BPH. The favorable comparison of saw palmetto with tamsulosin, a well-known first line agent in the treatment of urinary tract symptoms, demonstrates promise towards a beneficial effect of this herbal agent, with very few, if any, adverse effects. However, what degree of this beneficial activity is due to placebo effects is yet to be determined. In addition, the precise mechanism of action of saw palmetto in men with BPH remains unclear.

Benign Prostatic Hyperplasia: from Bench to Clinic

PubMed Central

Cho, Hee Ju

2012-01-01

Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study.

PubMed

Welk, Blayne; McArthur, Eric; Fraser, Lisa-Ann; Hayward, Jade; Dixon, Stephanie; Hwang, Y Joseph; Ordon, Michael

2015-10-26

Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147,084 men aged ≥ 66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥ 66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs. Prostate-specific α antagonists are associated with a small but significant increased risk of fall, fracture, and head trauma, probably as a result of induced hypotension. This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site through the Kidney, Dialysis, and Transplantation (KDT) research program. BW has received a research grant from Astellas, and L-AF does consultancy for Amgen. © Welk et al 2015.

Plant extracts: sense or nonsense?

PubMed

Madersbacher, Stephan; Berger, Ingrid; Ponholzer, Anton; Marszalek, Martin

2008-01-01

To assess the current role of plant extracts in the medical management of lower urinary tract symptoms due to benign prostatic enlargement/benign prostatic obstruction. In 2006, two clinical trials meeting the WHO benign prostatic hyperplasia consensus conference criteria (randomized against placebo/standard therapy, study duration 12 months) were published. One trial compared a saw palmetto extract with placebo. This industry-independent trial published in the New England Journal of Medicine was negative, that is, this saw palmetto extract had no effect on symptoms, Qmax and postvoid residual volume. In another trial, a saw palmetto/urtica combination was compared with tamsulosin. After 12 months, the improvement of symptoms was identical in both study arms. No detailed data were presented, however, on Qmax, postvoid residual or prostate volume. The biological mechanisms of plant extracts in vivo are still unknown and the numerous metaanalyses cannot supplement high-quality prospective trials. Further prospective studies according to WHO benign prostatic hyperplasia standards are required to reliably determine the role of plant extracts in contemporary lower urinary tract symptoms management and to be able to answer the question in the title: 'plant extracts: sense or nonsense?' Plant extracts are currently not recommended by the American and European Association of Urology benign prostatic hyperplasia guidelines.

Efficacy and safety of PDE5-Is and α-1 blockers for treating lower ureteric stones or LUTS: a meta-analysis of RCTs.

PubMed

Sun, Xifeng; Guan, Wei; Liu, Haoran; Tang, Kun; Yan, Libin; Zhang, Yangjun; Zeng, Jin; Chen, Zhiqiang; Xu, Hua; Ye, Zhangqun

2018-05-03

Lower ureteric stones and lower urinary tract symptoms are common in urology.Drug treatment is one of standard therapy,but the efficacy was controversial.Thus we aimed to investigate the efficacy and safety of monotherapy or combination therapy of adrenoceptor1 blockers and phosphodiesterase5 inhibitors for treatment. Randomized controlled trials up to November 2016 were retrieved from PubMed, the Cochrane Library, Web of Science and Embase. A total of 17 studies were included. We analyzed data through random or fixed effect models. The heterogeneity between studies was assessed by the I 2 test statistic. As for lower ureter stones, our analysis demonstrated tadalafil had a significantly lower incidence of abnormal ejaculation than adrenoceptor1 blockers (2.31 95%CI 0.22to0.84, P = 0.01),while combination therapy had a higher expulsion rate (2.49 95%CI 1.44to4.29, P = 0.001) and shorter expulsion time (- 1.98 95%CI -3.08to0.88, P = 0.0004) than tamsulosin. As for lower urinary tract symptoms, our analysis indicated adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on decreasing International Prostate Symptom Score (1.96 95%CI 0.03to3.89, P = 0.05) and Post-Void Residual (9.41 95%CI 1.40to14.41, P = 0.02) and phosphodiesterase5 inhibitors showed a greater effect than adrenoceptor1 blockers on improving Erectile Dysfunction (2.23 95%CI 1.24to3.22, P<0.0001).Combination therapy had a significantly better effect on International Prostate Symptom Score (1.47 95%CI 1.25to1.69, P<0.0001), Maximum flow rate (0.87 95%CI 0.71to1.04, P<0.0001), Post-Void Residual (10.74 95%CI 3.53to17.96,P = 0.004) and Quality of life (0.59 95%CI 0.22to0.97, P = 0.002) but was associated with higher incidences of adverse events (3.40 95%CI 1.82to6.36, P = 0.0001) than adrenoceptor1 blockers. Combination therapy had a significantly better effect on International Prostate Symptom Score (4.19 95%CI 3.34to5.04, P<0.0001), Maximum flow rate (1.86 95%CI 1.32to2.39, P<0.0001), Post-Void Residual (22.58 95%CI 9.13to36.04, P = 0.001) and Quality of life (0.68 95%CI 0.37to1.00, P<0.0001) without higher incidences of adverse events than PDE5-Is. In conclusion, this meta-analysis suggested combination therapy had a best efficacy of therapy for lower ureteric stones or lower urinary tract symptoms correlated with benign prostatic hyperplasia than monotherapy. Adrenoceptor1 blockers was more effective than phosphodiesterase5 inhibitors on International Prostate Symptom Score and Post-Void Residual. Both monotherapy and combination therapy were safe.

A pharmacoepidemiological approach to investigating inappropriate physician prescribing in a managed care setting in Israel.

PubMed

Kahan, Natan R; Blackman, Shimon; Kutz, Chaim; Waitman, Dan-Andrei

2005-02-01

To identify cases of inappropriate physician prescribing in a managed care setting in Israel that may have resulted from misuse of magnetic-stripe membership cards. Retrospective drug utilization analysis of electronic patient prescription data. In a managed care setting involving approximately 1000 physicians who issue approximately 1.4 million prescriptions annually, the rate of prescription of sex-specific drugs to patients of the opposite sex for which the drugs are indicated was evaluated for 2003. The categories of drugs included in the analysis were drugs for the treatment of benign prostatic hyperplasia or erectile dysfunction that were prescribed to women, as well as oral contraceptives, vaginal pessaries, hormone therapy, or raloxifene hydrochloride prescribed to men. Throughout the study year, 193 different physicians wrote 341 prescriptions that matched the drug inclusion criteria for 210 different patients. The most frequently observed scenario involved the prescription for women of selective alpha-blockers, including alfuzosin hydrochloride, tamsulosin hydrochloride, and terazosin hydrochloride, that are indicated exclusively for the treatment of benign prostatic hyperplasia. The electronic patient record system used in the health maintenance organization studied was programmed to block the prescription of sex-specific drugs for patients of the opposite sex for which they are intended unless proper authorization has been obtained. Furthermore, periodic investigation into prescription impropriety may be easily accomplished through the implementation of pharmacoepidemiological methods commonly used in drug utilization studies.

Histopathological classification criteria of rat model of chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Wang, Xianjin; Zhong, Shan; Xu, Tianyuan; Xia, Leilei; Zhang, Xiaohua; Zhu, Zhaowei; Zhang, Minguang; Shen, Zhoujun

2015-02-01

A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.

Superparamagnetic graphene oxide-based dispersive-solid phase extraction for preconcentration and determination of tamsulosin hydrochloride in human plasma by high performance liquid chromatography-ultraviolet detection.

PubMed

Pashaei, Yaser; Ghorbani-Bidkorbeh, Fatemeh; Shekarchi, Maryam

2017-05-26

In the present study, superparamagnetic graphene oxide-Fe 3 O 4 nanocomposites were successfully prepared by a modified impregnation method (MGO mi ) and their application as a sorbent in the magnetic-dispersive solid phase extraction (M-dSPE) mode to the preconcentration and determination of tamsulosin hydrochloride (TMS) in human plasma was investigated by coupling with high performance liquid chromatography-ultraviolet detection (HPLC-UV). The structure, morphology and magnetic properties of the prepared nanocomposites were characterized using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and vibrating sample magnetometry (VSM). Some factors affecting the extraction efficiency, including the pH value, amount of sorbent, extraction time, elution solvent and its volume, and desorption time were studied and optimized. Magnetic nanocomposites plasma extraction of TMS following HPLC analyses showed a linear calibration curve in the range of 0.5-50.0ngmL -1 with an acceptable correlation coefficient (R 2 =0.9988). The method was sensitive, with a low limit of detection (0.17ngmL -1 ) and quantification (0.48ngmL -1 ). Inter- and intra-day precision expressed as relative standard deviation (n=3) and the preconcentration factor, were found to be 5.6-7.2%, 2.9-4.2% and 10, respectively. Good recoveries (98.1-101.4%) with low relative standard deviations (4.2-5.0%) indicated that the matrices under consideration do not significantly affect the extraction process. Due to its high precision and accuracy, the developed method may be a HPLC-UV alternative with M-dSPE for bioequivalence analysis of TMS in human plasma. Copyright © 2017 Elsevier B.V. All rights reserved.

The risk of fall and fracture with the initiation of a prostate-selective α antagonist: a population based cohort study

PubMed Central

McArthur, Eric; Fraser, Lisa-Ann; Hayward, Jade; Dixon, Stephanie; Hwang, Y Joseph; Ordon, Michael

2015-01-01

Study question Do men starting treatment with prostate-specific α antagonists have increased risk of fall and fracture? Methods Administrative datasets from the province of Ontario, Canada, that contain patient level data were used to generate a cohort of 147 084 men aged ≥66 years who filled their first outpatient prescription for prostate-specific α antagonists tamsulosin, alfuzosin, or silodosin between June 2003 and December 2013 (exposed men) plus an equal sized cohort matched 1:1 (using a propensity score model) who did not initiate α antagonist therapy. The primary outcome was a hospital emergency room visit or inpatient admission for a fall or fracture in the 90 days after exposure. Study answer and limitations The men exposed to prostate-specific α antagonist had significantly increased risks of falling (odds ratio 1.14 (95% CI 1.07 to 1.21), absolute risk increase 0.17% (0.08 to 0.25%)) and of sustaining a fracture (odds ratio 1.16 (1.04 to 1.29), absolute risk increase 0.06% (0.02 to 0.11%)) compared with the unexposed cohort. This increased risk was not observed in the period before α antagonist use. Secondary outcomes of hypotension and head trauma were also significantly increased in the exposed cohort (odds ratios 1.80 (1.59 to 2.03) and 1.15 (1.04 to 1.27) respectively). The two cohorts were similar across 98 different covariates including demographics, comorbid conditions, medication use, healthcare use, and prior medical investigation. Potential unmeasured confounders, such as physical deconditioning, mobility impairment, and situational risk factors, may exist. The data used to identify the primary outcomes had limited sensitivity, so the absolute risks of the outcomes are probably underestimates. The study only included men ≥66 years old, and 84% of exposed men were prescribed tamsulosin, so results may not be generalizable to younger men, and there may not be statistical power to show small differences in outcomes between the drugs. What this study adds Prostate-specific α antagonists are associated with a small but significant increased risk of fall, fracture, and head trauma, probably as a result of induced hypotension. Funding, competing interests, data sharing This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site through the Kidney, Dialysis, and Transplantation (KDT) research program. BW has received a research grant from Astellas, and L-AF does consultancy for Amgen. PMID:26502947

Appropriateness of oral drugs for long-term treatment of lower urinary tract symptoms in older persons: results of a systematic literature review and international consensus validation process (LUTS-FORTA 2014).

PubMed

Oelke, Matthias; Becher, Klaus; Castro-Diaz, David; Chartier-Kastler, Emmanuel; Kirby, Mike; Wagg, Adrian; Wehling, Martin

2015-09-01

we aimed to systematically review drugs to treat lower urinary tract symptoms (LUTS) regularly used in older persons to classify appropriate and inappropriate drugs based on efficacy, safety and tolerability by using the Fit fOR The Aged (FORTA) classification. to evaluate the efficacy, safety and tolerability of drugs used for treatment of LUTS in older persons, a systematic review was performed. Papers on clinical trials and summaries of individual product characteristics were analysed regarding efficacy and safety in older persons (≥65 years). The most frequently used drugs were selected based on current prescription data. An interdisciplinary international expert panel assessed the drugs in a Delphi process. for the 16 drugs included here, a total of 896 citations were identified; of those, only 25 reported clinical trials with explicit data on, or solely performed in older people, underlining the lack of evidence in older people for drug treatment of LUTS. No drug was rated at the FORTA-A-level (indispensable). Only three were assigned to FORTA B (beneficial): dutasteride, fesoterodine and finasteride. The majority was rated FORTA C (questionable): darifenacin, mirabegron, extended release oxybutynin, silodosin, solifenacin, tadalafil, tamsulosin, tolterodine and trospium. FORTA D (avoid) was assigned to alfuzosin, doxazosin, immediate release oxybutynin, propiverine and terazosin. dutasteride, fesoterodine and finasteride were classified as beneficial in older persons or frail elderly people (FORTA B). For most drugs, in particular those from the group of α-blockers and antimuscarinics, use in this group seems questionable (FORTA C) or should be avoided (FORTA D). © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 4: Alpha blockers v calcium blockers to increase spontaneous passage of renal calculi.

PubMed

Stewart, Alexander; Ferguson, Craig

2013-02-01

A short cut review was carried out to establish the administration of an alpha-1 receptor antagonist or a calcium channel blocker would facilitate the most rapid and successful expulsion of a stone from a patient with uncomplicated renal colic. 597 articles were found using the reported search, of which five trials were selected as providing the best evidence to answer this question. The authors, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that in a patient with an uncomplicated ureteric calculus tamsulosin is more effective than nifedipine in promoting speedy and successful expulsion of the stone.

Intraoperative floppy iris syndrome and its association with various concurrent medications, bulbus length, patient age and gender.

PubMed

Wahl, Michael; Tipotsch-Maca, Saskia M; Vecsei-Marlovits, Pia V

2017-01-01

To evaluate the association between intraoperative floppy iris syndrome (IFIS) and concurrent medications containing selective alpha1A receptor antagonists as well as nonselective alpha1-adrenergic receptor antagonists, bulbus length, patient age and gender. We performed a prospective data acquisition of IFIS occurrence and grading, and retrospective evaluation of concurrent medications, bulbus length, patient age and gender of all patients undergoing cataract surgery over a 6-month period. IFIS was observed in 119 of 947 cases (12.6 %). 31 of those 119 patients (26.1 %) had a concurrent medication with a drug that is associated with a higher risk of causing IFIS. Tamsulosin was the drug most commonly associated with IFIS (n = 11), followed by a combination of drugs (n = 7), doxazosin (n = 4), quetiapine (n = 4), finasterid (n = 2), prothipendyl (n = 2), and mianserin (n = 1). Bulbus length and age did not show any significant association with occurrence or grade of IFIS. Gender distribution among IFIS cases was 57.1 % males (n = 68) and 42.9 % (n = 51) females. The occurrence of IFIS has to be expected with a variety of concurrent medications. The number of IFIS cases and the percentage of females in this series are higher compared to previous reports. The observations might be due to a rising awareness of surgeons or to an increasing number of causative medications on the market.

Saw palmetto extracts potently and noncompetitively inhibit human alpha1-adrenoceptors in vitro.

PubMed

Goepel, M; Hecker, U; Krege, S; Rübben, H; Michel, M C

1999-02-15

We wanted to test whether phytotherapeutic agents used in the treatment of lower urinary tract symptoms have alpha1-adrenoceptor antagonistic properties in vitro. Preparations of beta-sitosterol and extracts of stinging nettle, medicinal pumpkin, and saw palmetto were obtained from several pharmaceutical companies. They were tested for their ability to inhibit [3H]tamsulosin binding to human prostatic alpha1-adrenoceptors and [3H]prazosin binding to cloned human alpha1A- and alpha1B-adrenoceptors. Inhibition of phenylephrine-stimulated [3H]inositol phosphate formation by cloned receptors was also investigated. Up to the highest concentration which could be tested, preparations of beta-sitosterol, stinging nettle, and medicinal pumpkin were without consistent inhibitory effect in all assays. In contrast, all tested saw palmetto extracts inhibited radioligand binding to human alpha1-adrenoceptors and agonist-induced [3H]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active concentrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha1-adrenoceptor antagonists. Saw palmetto extracts have alpha1-adrenoceptor-inhibitory properties. If bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha1-adrenoceptor antagonists, alpha1-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction.

Benign prostatic hyperplasia (BPH) management in the primary care setting.

PubMed

Kapoor, Anil

2012-10-01

Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH.

The effect of sodium alginate on physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer.

PubMed

Kim, Min-Soo; Kim, Jeong-Soo; Hwang, Sung-Joo

2007-11-01

The aim of this study was to investigate the effect of sodium alginate on the physical and dissolution properties of Surelease-matrix pellets prepared by a novel pelletizer-equipped piston extruder and double-arm counter-rotating rollers. The mean values of the shape factor (e(R)) and the aspect ratio of Surelease-matrix pellets were 0.615-0.625 and 1.06-1.070, respectively, indicating good sphericity of the pellets. The drug release rate increased as the amount of sodium alginate increased due to hydration, swelling, and erosion within the Surelease-matrix pellets. In addition, the porosity of pellets also increased with increasing sodium alginate content. The results of this study show that sodium alginate has a greater effect on the drug release rate than the drug release mechanism within the Surelease-matrix for sparingly water-soluble drug, such as tamsulosin hydrochloride.

Evolving Guidance on Ureteric Calculi Management in the Acute Setting.

PubMed

Makanjuola, Jonathan K; Rintoul-Hoad, Sophie; Bultitude, Matthew

2016-03-01

Ureteric colic is a common presentation to acute emergency services. The gold standard test for the diagnosis of acute ureteric colic is a non-contrast computer tomography of the kidneys ureters and bladder (CT KUB). Non-steroidal anti-inflammatory drugs (NSAIDs) should be used as first-line analgesia, with studies showing that there is no role for steroid or phosphodiesterase-5 inhibitors. There is emerging evidence that a high body mass index (BMI) is a risk factor. The drugs used to facilitate stone passage are known as medical expulsive therapy (MET). The most evaluated being alpha-blockers. The Spontaneous Urinary Stone Passage Enabled by Drugs (SUSPEND) trial was designed to evaluate the use of MET (tamsulosin and nifedipine). This trial showed that there was no difference with MET and placebo for the spontaneous passage of ureteric stones. There is an emerging role for the use of primary ureteroscopy in the management of non-infective ureteric stones.

Gateways to clinical trials.

PubMed

Tomillero, A; Moral, M A

2009-06-01

(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Adrenoceptor function and expression in bladder urothelium and lamina propria.

PubMed

Moro, Christian; Tajouri, Lotti; Chess-Williams, Russ

2013-01-01

To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria). The responses of isolated strips of porcine urothelium/lamina propria to noradrenaline, phenylephrine, and isoprenaline were obtained in the absence and presence of receptor subtype-selective antagonists. Quantitative reverse-transcriptase polymerase chain reaction was undertaken to assess the expression of adrenoceptor genes. The tissues expressed all α1- and β-adrenoceptor subtypes, with the α1A-, α1B-, and β2-adrenoceptors the predominant receptors at the messenger RNA level. In the functional experiments, the rate of phasic contractions and the basal tension were increased by the α1-adrenoceptor agonists phenylephrine (100 μM) and A61603 (10 μM). The rate and tension responses to phenylephrine were reduced by low concentrations of tamsulosin (3 nM) and RS100329 (10 nM) but were unaffected by BMY7378 (100 nM), prazosin (10 nM), and RS17053 (1 μM). In contrast, isoprenaline and salbutamol (both 1 μM) induced a relaxation of tissues and slowing of phasic contractions. The rate and tension responses to isoprenaline were inhibited by propranolol (100 nM) or a combination of CGP20712A (30 nM) and ICI118551 (70 nM). The rate responses were also significantly inhibited by ICI118551 alone (70 nM). Although all α1- and β-adrenoceptor subtypes were expressed in the pig urothelium/lamina propria, the α1A/L-adrenoceptor appeared to mediate increases in the contractile rate and tension. The β-adrenoceptor induced inhibition of spontaneous contractile activity appears to be predominately mediated by β2-adrenoceptors, with β1- and β2-adrenoceptors possibly involved in the tension responses. Copyright © 2013 Elsevier Inc. All rights reserved.

7 CFR 305.10 - Treatment schedules for combination treatments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Treatment schedules for combination treatments. 305.10... HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE PHYTOSANITARY TREATMENTS Chemical Treatments § 305.10 Treatment schedules for combination treatments. (a) Fumigation followed by cold treatment. (1...

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

PubMed

Masoudzadeh, A; Khalilian, A R

2007-12-01

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

The combined use of virtual reality exposure in the treatment of agoraphobia.

PubMed

Pitti, Carmen T; Peñate, Wenceslao; de la Fuente, Juan; Bethencourt, Juan M; Roca-Sánchez, María J; Acosta, Leopoldo; Villaverde, María L; Gracia, Ramón

2015-01-01

This study compares the differential efficacy of three groups of treatments for agoraphobia: paroxetine combined with cognitive-behavioral therapy, paroxetine combined with cognitive-behavioral therapy and virtual reality exposure, and a group with only paroxetine. 99 patients with agoraphobia were finally selected. Both combined treatment groups received 11 sessions of cognitive-behavioral therapy, and one of the groups was also exposed to 4 sessions of virtual reality treatment. Treatments were applied in individual sessions once a week for 3 months. The three treatment groups showed statistically significant improvements. In some measures, combined treatment groups showed greater improvements. The virtual reality exposure group showed greater improvement confronting phobic stimuli. Treatments combining psychopharmacological and psychological therapy showed greater efficacy. Although the use of new technologies led to greater improvement, treatment adherence problems still remain.

Acquired resistance to combination treatment through loss of synergy with MEK and PI3K inhibitors in colorectal cancer

PubMed Central

Bhattacharya, Bhaskar; Low, Sarah Hong Hui; Chong, Mei Ling; Chia, Dilys; Koh, King Xin; Sapari, Nur Sabrina; Kaye, Stanley; Hung, Huynh; Benoukraf, Touati; Soong, Richie

2016-01-01

Historically, understanding of acquired resistance (AQR) to combination treatment has been based on knowledge of resistance to its component agents. To test whether an altered drug interaction could be an additional factor in AQR to combination treatment, models of AQR to combination and single agent MEK and PI3K inhibitor treatment were generated. Combination indices indicated combination treatment of PI3K and MEK inhibitors remained synergistic in cells with AQR to single agent but not combination AQR cells. Differences were also observed between the models in cellular phenotypes, pathway signaling and drug cross-resistance. Genomics implicated TGFB2-EDN1 overexpression as candidate determinants in models of AQR to combination treatment. Supplementation of endothelin in parental cells converted synergism to antagonism. Silencing of TGFB2 or EDN1 in cells with AQR conferred synergy between PI3K and MEK inhibitor. These results highlight that AQR to combination treatment may develop through alternative mechanisms to those of single agent treatment, including a change in drug interaction. PMID:27081080

Efficacy of an alpha1 blocker in expulsive therapy of lower ureteral stones.

PubMed

Wang, Chung-Jing; Huang, Shi-Wei; Chang, Chien-Hsing

2008-01-01

To evaluate the clinical role of an alpha(1a-1d)-specific blocker in the medical expulsive therapy of symptomatic lower ureteral stones. This prospective study was carried out from May 2005 to December 2006 and involved 95 patients. All patients, who had symptomatic lower ureteral stones <10 mm diameter, were enrolled in this prospective study, and were randomly divided into three groups using the statistical software programs Plus 1.0 and Plus 2.10. Group 1 (32 patients) received tamsulosin (0.4 mg daily), group 2 (32 patients) received terazosin (2 mg daily), group 3 (31 patients) acted as controls. All patients were diagnosed with x-rays of the kidneys, ureters, and bladder, urinary ultrasonography, and intravenous urography. All patients received the same analgesic regimen and sublingual buprenorphine on demand. The number of colic episodes, lower urinary tract symptoms, analgesic dosages, and the number of days required for spontaneous passage of the stones were all recorded in a diary. Expulsion was observed in 26 of 32 patients in group 1 (81%), 25 of 32 in group 2 (78%), and 17 of 31 in group 3 (55%). The average expulsion time for groups 1, 2, and 3 were 6.3, 6.3, and 10.1 days, respectively. Mean analgesic dosage per patient in groups 1, 2, and 3 were 231, 256, and 347 mg, respectively. A statistically significant difference was observed between groups 1 and 2 with respect to group 3 for all three of these parameters. Adverse effects were also seen in 5 of 32 patients in group 2 (16%), a statistically significant difference with regard to groups 1 and 3. Medical treatment with alpha(1a-1d)-blocker proved to be safe and effective as demonstrated by the increased stone expulsion rate and reduced expulsion time, as well as the need for analgesics.

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia

PubMed Central

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B.; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-01-01

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis. PMID:27529214

Apoptotic Pathways Linked to Endocrine System as Potential Therapeutic Targets for Benign Prostatic Hyperplasia.

PubMed

Minutoli, Letteria; Rinaldi, Mariagrazia; Marini, Herbert; Irrera, Natasha; Crea, Giovanni; Lorenzini, Cesare; Puzzolo, Domenico; Valenti, Andrea; Pisani, Antonina; Adamo, Elena B; Altavilla, Domenica; Squadrito, Francesco; Micali, Antonio

2016-08-11

Benign prostatic hyperplasia (BPH) is a chronic condition common in older men that can result in bothersome lower urinary tract symptoms. The molecular mechanisms and networks underlying the development and the progression of the disease are still far from being fully understood. BPH results from smooth muscle cell and epithelial cell proliferation, primarily within the transition zone of the prostate. Apoptosis and inflammation play important roles in the control of cell growth and in the maintenance of tissue homeostasis. Disturbances in molecular mechanisms of apoptosis machinery have been linked to BPH. Increased levels of the glycoprotein Dickkopf-related protein 3 in BPH cause an inhibition of the apoptosis machinery through a reduction in B cell lymphoma (Bcl)-2 associated X protein (Bax) expression. Inhibitors of apoptosis proteins influence cell death by direct inhibition of caspases and modulation of the transcription factor nuclear factor-κB. Current pharmacotherapy targets either the static component of BPH, including finasteride and dutasteride, or the dynamic component of BPH, including α-adrenoceptor antagonists such as tamsulosin and alfuzosin. Both these classes of drugs significantly interfere with the apoptosis machinery. Furthermore, phytotherapic supplements and new drugs may also modulate several molecular steps of apoptosis.

Cost-effectiveness and cost-utility of combination therapy in early rheumatoid arthritis: randomized comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone. COBRA Trial Group. Combinatietherapie Bij Reumatoïde Artritis.

PubMed

Verhoeven, A C; Bibo, J C; Boers, M; Engel, G L; van der Linden, S

1998-10-01

Assessment of the cost-effectiveness and cost-utility of early intervention in rheumatoid arthritis (RA) patients, with combined step-down prednisolone, methotrexate and sulphasalazine, compared to sulphasalazine alone. Multicentre 56 week randomized double-blind trial with full economic analysis of direct costs and utility analysis with rating scale and standard gamble measurement techniques. The combined-treatment group included 76 patients and the sulphasalazine group 78 patients. The mean total costs per patient in the first 56 weeks of follow-up were $5519 for combined treatment and $6511 for treatment with sulphasalazine alone (P = 0.37). Out-patient care, in-patient care and non-health care each contributed about one-third to the total costs. The combined-treatment group appeared to generate savings in the length of hospital stay for RA, non-protocol drugs and costs of home help, but comparisons were not statistically significant. Protocol drugs and monitoring were slightly more expensive in the combined-treatment group. Clinical, radiographic and functional outcomes significantly favoured combined treatment at week 28 (radiography also at week 56). Utility scores also favoured combined treatment. Combined treatment is cost-effective due to enhanced efficacy at lower or equal direct costs.

Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model

PubMed Central

Specht, Sabine; Arriens, Sandra; Hübner, Marc P.; Klarmann-Schulz, Ute; Koschel, Marianne; Sternberg, Sonja; Martin, Coralie; Taylor, Mark J.; Hoerauf, Achim

2018-01-01

Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4–6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7–10 days of treatment. PMID:29300732

Combinations of registered drugs reduce treatment times required to deplete Wolbachia in the Litomosoides sigmodontis mouse model.

PubMed

Specht, Sabine; Pfarr, Kenneth M; Arriens, Sandra; Hübner, Marc P; Klarmann-Schulz, Ute; Koschel, Marianne; Sternberg, Sonja; Martin, Coralie; Ford, Louise; Taylor, Mark J; Hoerauf, Achim

2018-01-01

Filarial parasites can be targeted by antibiotic treatment due to their unique endosymbiotic relationship with Wolbachia bacteria. This finding has led to successful treatment strategies in both, human onchocerciasis and lymphatic filariasis. A 4-6 week treatment course using doxycycline results in long-term sterility and safe macrofilaricidal activity in humans. However, current treatment times and doxycycline contraindications in children and pregnant women preclude widespread administration of doxycycline in public health control programs; therefore, the search for shorter anti-wolbachial regimens is a focus of ongoing research. We have established an in vivo model for compound screening, using mice infected with Litomosoides sigmodontis. We could show that gold standard doxycycline treatment did not only deplete Wolbachia, it also resulted in a larval arrest. In this model, combinations of registered antibiotics were tested for their anti-wolbachial activity. Administration of rifamycins in combination with doxycycline for 7 days successfully depleted Wolbachia by > 2 log (>99% reduction) and thus resulted in a significant reduction of the treatment duration. Using a triple combination of a tetracycline (doxycycline or minocycline), a rifamycin and a fluoroquinolone (moxifloxacin) led to an even greater shortening of the treatment time. Testing all double combinations that could be derived from the triple combinations revealed that the combination of rifapentine (15mg/kg) and moxifloxacin (2 x 200mg/kg) showed the strongest reduction of treatment time in intraperitoneal and also oral administration routes. The rifapentine plus moxifloxacin combination was equivalent to the triple combination with additional doxycycline (>99% Wolbachia reduction). These investigations suggest that it is possible to shorten anti-wolbachial treatment times with combination treatments in order to achieve the target product profile (TPP) requirements for macrofilaricidal drugs of no more than 7-10 days of treatment.

Additive naftopidil treatment synergizes docetaxel-induced apoptosis in human prostate cancer cells.

PubMed

Ishii, Kenichiro; Matsuoka, Izumi; Kajiwara, Shinya; Sasaki, Takeshi; Miki, Manabu; Kato, Manabu; Kanda, Hideki; Arima, Kiminobu; Shiraishi, Taizo; Sugimura, Yoshiki

2018-01-01

Docetaxel (DTX) is a standard chemotherapeutic drug for castration-resistant prostate cancer (CRPC), although adverse events are common. To overcome this problem, researchers have evaluated the efficacy of DTX treatment in combination with other drugs. Naftopidil is a tubulin-binding drug with fewer adverse events, implying the usefulness of this drug in clinical applications when combined with DTX. Here, we investigated the efficacy of additive naftopidil treatment in combination with DTX on prostate cancer (PCa) cells. The effects of combination treatment with DTX plus naftopidil were analyzed using two animal models of LNCaP cells plus PrSC xenografts (sub-renal capsule grafting) and PC-3 xenografts (intratibial injection). Combination treatment with DTX plus naftopidil significantly inhibited cell growth in LNCaP cells compared with DTX alone. Analysis of the cooperativity index (CI) showed that combination treatment exhibited additive effects on DTX-induced growth inhibition in LNCaP cells. In contrast, combination treatment showed more than an additive (synergistic) effect on DTX-induced apoptosis in LNCaP and PC-3 cells. In LNCaP cells plus PrSC xenografts, combination treatment showed synergistic effects on DTX-induced apoptosis. The synergistic effects of naftopidil on DTX-induced apoptosis were also observed in PC-3 xenografts. Our results demonstrated that additive naftopidil treatment in combination with DTX increased the efficacy of DTX for the treatment of LNCaP and PC-3 tumors in vivo. Thus, additive naftopidil treatment showed a synergistic effect on DTX-induced apoptosis in PCa cells in vitro and in vivo, suggesting that this treatment approach may yield improved clinical benefits compared with DTX alone.

Comparison of single and combination treatments of Phytoseiulus persimilis, Neoseiulus californicus, and Acramite (bifenazate) for control of twospotted spider mites in strawberries.

PubMed

Rhodes, Elena M; Liburd, Oscar E; Kelts, Crystal; Rondon, Silvia I; Francis, Roger R

2006-01-01

Greenhouse and field experiments were conducted from 2003 to 2005 to determine the effectiveness of combining releases of two predatory mite species, Phytoseiulus persimilis Athias-Henriot and Neoseiulus californicus (McGregor), and a reduced-risk miticide, Acramite (bifenazate), for control of twospotted spider mite (TSSM) (Tetranychus urticae Koch) in strawberries. In the greenhouse experiment, a combination treatment of P. persimilis and N. californicus was compared with single treatments of each species, Acramite application, and untreated control. All treatments significantly reduced TSSM numbers compared with the control. Field studies employed two approaches: one investigating the same five treatments as the greenhouse experiment and a second, comparing combination treatments of P. persimilis/N. californicus, Acramite/N. californicus, and Acramite/P. persimilis to single treatments of each and to control plots. Among the combination treatments, the P. persimilis/N. californicus treatment significantly reduced TSSM numbers compared with the control, but was not as effective as N. californicus alone during the 2003-2004 field season. Also, combination treatments of Acramite/N. californicus, and Acramite/P. persimilis significantly reduced TSSM populations compared with the control. These findings indicate that all three combination treatments are promising options for TSSM control in strawberries for growers in northern Florida and other strawberry producing areas of the world.

Bayesian adaptive phase II screening design for combination trials.

PubMed

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial.

[Combined treatment supported by piracetam and/or acyclovir in idiopathic sudden sensorineural hearing loss: experience with 81 cases].

PubMed

Karakurt, Süleyman Emre; Ozkul, Mehmet Doğan; Cukurova, Ibrahim; Demirhan, Erhan; Yiğitbaşi, Orhan Gazi

2009-01-01

To investigate the efficiency of piracetam and acyclovir in treating sudden hearing loss. Eightyone patients (44 males, 37 females; mean age 40.4 year; range 18 to 72 years) who had treatment between January 2002 and December 2006 with diagnosis of idiopathic sudden hearing loss were evaluated retrospectively. These patients were divided into four groups according to the treatment they received. The patients who had combined treatment constituted the first group; those who had combined treatment and piracetam the second; those who had combined treatment and acyclovir the third; those who had combined treatment, acyclovir, and piracetam the fourth group. For the four treatment groups, in the pre-and post-treatment (10th day) evaluation of the treatment efficiency made by calculation of the hearing thresholds in 250-8000 Hz frequencies, no significant difference between the groups was determined (p>0.05). No additional benefit was obtained with acyclovir and piracetam in treatment.

A Pilot Study on the Combination of Applied Behavior Analysis and Bumetanide Treatment for Children with Autism.

PubMed

Du, Lin; Shan, Ling; Wang, Bing; Li, Honghua; Xu, Zhida; Staal, Wouter G; Jia, Feiyong

2015-09-01

The purpose of this study was to investigate the therapeutic effects of combined bumetanide and applied behavior analysis (ABA) treatment in children with autism. Sixty children diagnosed with autism according to the International Classification of Diseases, Tenth Revision (ICD-10) criteria (mean age of 4.5 years) were randomly divided into two groups: A single treatment group (n=28) and a combined treatment group (n=32). The combined treatment group received ABA training combined with oral bumetanide (0.5 mg twice a day). The single treatment group received ABA training only. Autism symptoms were evaluated with the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS), whereas severity of disease (SI) and global improvement (GI) were measured with the Clinical Global Impressions (CGI). Assessment of ABC, CARS, and CGI was performed immediately before and 3 months after initiation of the treatment(s). Prior to intervention(s) no statistically significant differences in scores on the ABC, CARS, SI, or GI were found between the two groups. Total scores of the ABC, CARS, and SI were decreased in both groups after 3 months (p<0.05) compared with the scores prior to treatment. The total scores of the ABC and the CGI were significantly (p<0.05) lower in the combined treatment group than in the single treatment group. Although the total and item scores of the CARS in the combined treatment group were lower than in the single treatment group after a 3 month intervention, they did not reach statistical significance. No adverse effects of bumetanide were observed. Treatment with bumetanide combined with ABA training may result in a better outcome in children with autism than ABA training alone.

Comparing Treatments for Children with ADHD and Word Reading Difficulties: A Randomized Clinical Trial

PubMed Central

Tamm, Leanne; Denton, Carolyn A.; Epstein, Jeffery N.; Schatschneider, Christopher; Taylor, Heather; Arnold, L. Eugene; Bukstein, Oscar; Anixt, Julia; Koshy, Anson; Newman, Nicholas C.; Maltinsky, Jan; Brinson, Patricia; Loren, Richard; Prasad, Mary R.; Ewing-Cobbs, Linda; Vaughn, Aaron

2017-01-01

Objective This randomized clinical trial compared Attention-Deficit/Hyperactivity Disorder (ADHD) treatment alone, intensive reading intervention alone, and their combination for children with ADHD and word reading difficulties and disabilities (RD). Method Children (n=216; predominantly African American males) in grades 2–5 with ADHD and word reading/decoding deficits were randomized to ADHD treatment (carefully-managed medication+parent training), reading treatment (intensive reading instruction), or combined ADHD+reading treatment. Outcomes were parent and teacher ADHD ratings and measures of word reading/decoding. Analyses utilized a mixed models covariate-adjusted gain score approach with post-test regressed onto pretest and other predictors. Results Inattention and hyperactivity/impulsivity outcomes were significantly better in the ADHD (parent Hedges g=.87/.75; teacher g=.67/.50) and combined (parent g=1.06/.95; teacher g=.36/41) treatment groups than reading treatment alone; the ADHD and Combined groups did not differ significantly (parent g=.19/.20; teacher g=.31/.09). Word reading and decoding outcomes were significantly better in the reading (word reading g=.23; decoding g=.39) and combined (word reading g=.32; decoding g=.39) treatment groups than ADHD treatment alone; reading and combined groups did not differ (word reading g=.09; decoding g=.00). Significant group differences were maintained at the three- to five-month follow-up on all outcomes except word reading. Conclusions Children with ADHD and RD benefit from specific treatment of each disorder. ADHD treatment is associated with more improvement in ADHD symptoms than RD treatment, and reading instruction is associated with better word reading and decoding outcomes than ADHD treatment. The additive value of combining treatments was not significant within disorder, but the combination allows treating both disorders simultaneously. PMID:28333510

Comparing treatments for children with ADHD and word reading difficulties: A randomized clinical trial.

PubMed

Tamm, Leanne; Denton, Carolyn A; Epstein, Jeffery N; Schatschneider, Christopher; Taylor, Heather; Arnold, L Eugene; Bukstein, Oscar; Anixt, Julia; Koshy, Anson; Newman, Nicholas C; Maltinsky, Jan; Brinson, Patricia; Loren, Richard E A; Prasad, Mary R; Ewing-Cobbs, Linda; Vaughn, Aaron

2017-05-01

This trial compared attention-deficit/hyperactivity disorder (ADHD) treatment alone, intensive reading intervention alone, and their combination for children with ADHD and word reading difficulties and disabilities (RD). Children (n = 216; predominantly African American males) in Grades 2-5 with ADHD and word reading/decoding deficits were randomized to ADHD treatment (medication + parent training), reading treatment (reading instruction), or combined ADHD + reading treatment. Outcomes were parent and teacher ADHD ratings and measures of word reading/decoding. Analyses utilized a mixed models covariate-adjusted gain score approach with posttest regressed onto pretest. Inattention and hyperactivity/impulsivity outcomes were significantly better in the ADHD (parent Hedges's g = .87/.75; teacher g = .67/.50) and combined (parent g = 1.06/.95; teacher g = .36/41) treatment groups than reading treatment alone; the ADHD and Combined groups did not differ significantly (parent g = .19/.20; teacher g = .31/.09). Word reading and decoding outcomes were significantly better in the reading (word reading g = .23; decoding g = .39) and combined (word reading g = .32; decoding g = .39) treatment groups than ADHD treatment alone; reading and combined groups did not differ (word reading g = .09; decoding g = .00). Significant group differences were maintained at the 3- to 5-month follow-up on all outcomes except word reading. Children with ADHD and RD benefit from specific treatment of each disorder. ADHD treatment is associated with more improvement in ADHD symptoms than RD treatment, and reading instruction is associated with better word reading and decoding outcomes than ADHD treatment. The additive value of combining treatments was not significant within disorder, but the combination allows treating both disorders simultaneously. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Enhanced bactericidal effect of enterocin AS-48 in combination with high-intensity pulsed-electric field treatment against Salmonella enterica in apple juice.

PubMed

Martínez Viedma, Pilar; Sobrino López, Angel; Ben Omar, Nabil; Abriouel, Hikmate; Lucas López, Rosario; Valdivia, Eva; Martín Belloso, Olga; Gálvez, Antonio

2008-12-10

The effect of the broad spectrum cyclic antimicrobial peptide enterocin AS-48 combination with high-intensity pulsed-electric field (HIPEF) treatment (35 kV/cm, 150 Hz, 4 micros and bipolar mode) was tested on Salmonella enterica CECT 915 in apple juice. A response surface methodology was applied to study the bactericidal effects of the combined treatment. The process variables were AS-48 concentration, temperature, and HIPEF treatment time. While treatment with enterocin AS-48 alone up to 60 microg/ml had no effect on the viability of S. enterica in apple juice, an increased bactericidal activity was observed in combination with HIPEF treatments. Survival fraction was affected by treatment time, enterocin AS48 concentration and treatment temperature. The combination of 100 micros of HIPEF treatment, 30 microg/ml of AS-48, and temperature of 20 degrees C resulted in the lowest inactivation, with only a 1.2-log reduction. The maximum inactivation of 4.5-log cycles was achieved with HIPEF treatment for 1000 micros in combination with 60 microg/ml of AS-48 and a treatment temperature of 40 degrees C. Synergism between enterocin AS-48 and HIPEF treatment depended on the sequence order application, since it was observed only when HIPEF was applied in the presence of previously-added bacteriocin. The combined treatment could improve the safety of freshly-made apple juice against S. enterica transmission.

Treatment of selective mutism based on cognitive behavioural therapy, psychopharmacology and combination therapy - a systematic review.

PubMed

Østergaard, Kasper Rud

2018-05-01

Selective mutism (SM) is a debilitating childhood anxiety disorder characterized by a persistent lack of speech in certain social settings and is considered hard to treat. Cognitive behavioral therapy (CBT) and pharmacological treatments are the best described treatments in the literature. To test whether there is evidence on treatment based on CBT, medication or a combination of these. Systematic and critical review of the literature on CBT and/or pharmacological treatments of SM. Literature was sought on PubMed, Embase and Psycinfo in March 2017. Of the included studies, six examined CBT, seven pharmacologic treatment and two a combination of these. Using CBT 53/60 children improved symptomatically whilst respectively 55/67 and 6/7 improved using pharmacologic- and combination-treatment. Pharmacologic treatment and especially CBT showed promising results supported by some degree of evidence, which combination treatment lacks. Yet small numbers, few RCTs, heterogeneous study designs, lack of consistent measures, short treatment and follow-up periods, generally limits the evidence. This needs focus in future research.

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models

PubMed Central

Luo, Yong; Azad, Abul Kalam; Karanika, Styliani; Basourakos, Spyridon P.; Zuo, Xuemei; Wang, Jianxiang; Yang, Luan; Yang, Guang; Korentzelos, Dimitrios; Yin, Jianhua; Park, Sanghee; Zhang, Penglie; Campbell, James J.; Schall, Thomas J.; Cao, Guangwen; Li, Likun

2018-01-01

Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4‐2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub‐G1) in VCaP and C4‐2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p‐EGFR (Y1068), p‐AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133‐4 patient‐derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 μm2) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control‐treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors. PMID:29277895

Bayesian adaptive phase II screening design for combination trials

PubMed Central

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Background Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Methods Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Results Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. Limitations The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. Conclusions The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial. PMID:23359875

Sewage sludge disintegration by combined treatment of alkaline+high pressure homogenization.

PubMed

Zhang, Yuxuan; Zhang, Panyue; Zhang, Guangming; Ma, Weifang; Wu, Hao; Ma, Boqiang

2012-11-01

Alkaline pretreatment combined with high pressure homogenization (HPH) was applied to promote sewage sludge disintegration. For sewage sludge with a total solid content of 1.82%, sludge disintegration degree (DD(COD)) with combined treatment was higher than the sum of DD(COD) with single alkaline and single HPH treatment. NaOH dosage ⩽0.04mol/L, homogenization pressure ⩽60MPa and a single homogenization cycle were the suitable conditions for combined sludge treatment. The combined sludge treatment showed a maximum DD(COD) of 59.26%. By regression analysis, the combined sludge disintegration model was established as 11-DD(COD)=0.713C(0.334)P(0.234)N(0.119), showing that the effect of operating parameters on sludge disintegration followed the order: NaOH dosage>homogenization pressure>number of homogenization cycle. The energy efficiency with combined sludge treatment significantly increased compared with that with single HPH treatment, and the high energy efficiency was achieved at low homogenization pressure with a single homogenization cycle. Copyright © 2012 Elsevier Ltd. All rights reserved.

Application of combined treatment for control of Botrytis cinerea in phytosanitary irradiation processing

NASA Astrophysics Data System (ADS)

Jung, Koo; Yoon, Minchul; Park, Hae-Jun; Youll Lee, Kwang; Jeong, Rae-Dong; Song, Beom-Seok; Lee, Ju-Woon

2014-06-01

Phytosanitary treatments are required to disinfest quarantine pests and pathogens in agricultural commodities. Gray mold in fruit is caused by Botrytis cinerea, which is one of the major postharvest pathogen of apple and pear. Irradiation treatment is a viable alternative for phytosanitary purposes and a useful nonchemical method for controlling pests and postharvest pathogens. An irradiation dose of over 0.4 kGy is used for the control of insects and fungal disease in fresh fruit, but a loss of firmness occurs. Combined treatments are needed to reduce the irradiation dose in phytosanitary irradiation processing. This study focuses on the application of combined treatments to reduce the loss of fruit quality when fresh fruit is irradiated for phytosanitary purposes. Comparing the antifungal activity against B. cinerea, while gamma irradiation showed no antifungal activity at a dose of 1.0 kGy, combined treatments (nano Ag particle, nano-sized silica silver) at a dose of 1.0 kGy showed the strongest antifungal activity. This study demonstrates the synergistic impacts of combined treatments in phytosanitary irradiation processing. Taken together, the combined treatments may affect reduction of fruit injury that occurred with irradiation only, meaning that the use of combined treatments with gamma irradiation is significantly effective for the preservation of fruit quality.

Atorvastatin calcium in combination with methylprednisolone for the treatment of multiple sclerosis relapse.

PubMed

Li, Xiao-ling; Zhang, Zhen-chang; Zhang, Bo; Jiang, Hua; Yu, Chun-mei; Zhang, Wen-jing; Yan, Xiang; Wang, Man-xia

2014-12-01

This study aimed to investigate the efficacy of combined atorvastatin calcium and methylprednisolone for the treatment of multiple sclerosis relapse. Patients with multiple sclerosis (MS) at the relapse phase were randomized to receive either combined treatment of atorvastatin calcium and methylprednisolone (n = 19) or methylprednisolone alone (n = 19). Expanded Disability Status Scale (EDSS) was administered at baseline, 1 week, 2 weeks, 4 weeks, 3 months, and 6 months after treatment initiation. The number and volume of brain lesions were evaluated using magnetic resonance imaging at baseline and 6 months. The levels of IL-13, IL-35, IFN-γ, and IL-10 in the cerebrospinal fluid were examined using the enzyme-linked immunosorbent assay method. There was no significant difference in EDSS scores at 1, 2, and 4 weeks. At 3 and 6 months, the combined treatment group showed significantly lower EDSS scores than the monotherapy group (P < 0.05). The number and volume of brain lesions in the combined treatment group were significantly lower than the monotherapy group at 6 months (P < 0.001). The mean time to relapse was significantly extended in the combined treatment group than the monotherapy group (P < 0.001). At 2 and 4 weeks, the combined treatment group had significantly higher levels of IL-13, IL-35, and IL-10 in the cerebrospinal fluid than the monotherapy group (P < 0.05), but significantly lower level of IFN-γ (P < 0.001). The levels of IL-13 and IL-10 in the combined treatment group were positively correlated with EDSS scores (r = 0.632, P = 0.001; r = 0.731, P = 0.002). Combined treatment with atorvastatin calcium and methylprednisolone can improve the outcomes of MS relapse compared with glucocorticosteroid alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Efficacy of combined orthodontic-periodontic treatment for patients with periodontitis and its effect on inflammatory cytokines: A comparative study.

PubMed

Zhang, Jin; Zhang, Ai-Min; Zhang, Zong-Mei; Jia, Jin-Lin; Sui, Xin-Xin; Yu, Lu-Rui; Liu, Hai-Tao

2017-10-01

In this study, we aimed to investigate the efficacy of combined orthodontic-periodontic treatment in the treatment of patients with periodontitis and its effects on the levels of inflammatory cytokines. A total of 117 patients with periodontitis were randomly assigned to the basic group (receiving basic periodontic treatment, n = 58) and the combined group (receiving combined orthodontic-periodontic treatment, n = 59). In addition, 52 healthy people without periodontal disease were selected as the normal group. Probing depth, tooth mobility, plaque index, clinical attachment level, and sulcus bleeding index were recorded. ELISA was applied to detect gingival crevicular fluid (GCF) and serum levels of inflammatory cytokines. A 2-year clinical follow-up was conducted. Before treatment, the periodontal parameters (probing depth, tooth mobility, plaque index, clinical attachement level, and sulcus bleeding index) and GCF and serum levels of inflammatory cytokines (high-sensitivity C-reactive protein, interleukin-1β, interleukin-5, interleukin-6, interleukin-8, tumor necrosis factor-α, and prostaglandin E2) in the combined and basic groups were higher than those in the normal group. After 6 and 18 months of treatment, the periodontal parameters and GCF and serum levels of inflammatory cytokines decreased in the combined and basic groups. The periodontal parameters and the GCF and serum levels of inflammatory cytokines in the combined group were significantly lower than those in the basic group after 18 months of treatment. The combined group had a lower recurrence rate compared with the basic group. Combined orthodontic-periodontic treatment had good clinical efficacy in the treatment of periodontitis and could effectively decrease the levels of inflammatory cytokines. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2013-10-01

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

Recent Advances in Delivery of Drug-Nucleic Acid Combinations for Cancer Treatment

PubMed Central

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-01-01

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. PMID:23624358

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

PubMed

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Additional increased effects of mannitol-temozolomide combined treatment on blood-brain barrier permeability.

PubMed

Choi, Chunggab; Kim, Hye Min; Shon, Jeeheun; Park, Jiae; Kim, Hyeong-Taek; Oh, Seung-Hun; Kim, Nam Keun; Kim, Ok Joon

2018-03-04

The blood-brain barrier (BBB) is major obstacle in drug or stem cell treatment in chronic stroke. We hypothesized that adding mannitol to temozolomide (TMZ) is a practically applicable method for resolving the low efficacy of intravenous mannitol therapy. In this study, we investigated whether BBB permeability could be increased by this combined treatment. First, we established a chronic ischemic stroke rat model and examined changes in leakage of Evans blue dye within a lesion site, and in expression of tight junction proteins (TJPs), by this combined treatment. Additionally, in an in vitro BBB model using trans-wells, we analyzed changes in diffusion of a fluorescent tracer and in expression of TJPs. Mannitol-TMZ combined treatment not only increased the amount of Evans blue dye within the stroke lesion site, but also reduced occludin expression in rat brain microvessels. The in vitro study also showed that combined treatment increased the permeability for two different-sized fluorescent tracers, especially large size, and decreased expression of TJPs, such as occludin and ZO-1. Increased BBB permeability effects were more prominent with combined than with single treatments. Mannitol-TMZ combined treatment induced a decrease of TJPs with a consequent increase in BBB permeability. This combined treatment is clinically useful and might provide new therapeutic options by enabling efficient intracerebral delivery of various drugs that could not otherwise be used to treat many CNS diseases due to their inability to penetrate the BBB. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2010-05-01

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

Surgical Treatment and Rehabilitation of Combined Complex Ligament Injuries

PubMed Central

Romeyn, Richard L.; Jennings, Jason

2008-01-01

This article is a description of the surgical treatment and rehabilitation of combined complex ligament injuries. A background will be provided, and information on the combined complex knee injuries, selected aspects of surgical treatments, and rehabilitation strategies will be presented. Combined complex ligament injuries are devastating injuries and are not very common compared to other knee injuries. No meta-analysis or systematic review studies exist regarding the best treatments for these patients. This article's emphasis is on the stages in the rehabilitation program with documentation of the scientific and clinical rationale for the treatment techniques in each stage. Treatment interventions are described and documented with the limited evidence available in treating these patients. Guidelines for treatment, surgery, and a clinical protocol for treating patients with combined complex ligament injuries are provided for the practicing clinician to use as a template for treating these complicated patients. PMID:21509123

Improving the sludge disintegration efficiency of sonication by combining with alkalization and thermal pre-treatment methods.

PubMed

Şahinkaya, S; Sevimli, M F; Aygün, A

2012-01-01

One of the most serious problems encountered in biological wastewater treatment processes is the production of waste activated sludge (WAS). Sonication, which is an energy-intensive process, is the most powerful sludge pre-treatment method. Due to lack of information about the combined pre-treatment methods of sonication, the combined pre-treatment methods were investigated and it was aimed to improve the disintegration efficiency of sonication by combining sonication with alkalization and thermal pre-treatment methods in this study. The process performances were evaluated based on the quantities of increases in soluble chemical oxygen demand (COD), protein and carbohydrate. The releases of soluble COD, carbohydrate and protein by the combined methods were higher than those by sonication, alkalization and thermal pre-treatment alone. Degrees of sludge disintegration in various options of sonication were in the following descending order: sono-alkalization > sono-thermal pre-treatment > sonication. Therefore, it was determined that combining sonication with alkalization significantly improved the sludge disintegration and decreased the required energy to reach the same yield by sonication. In addition, effects on sludge settleability and dewaterability and kinetic mathematical modelling of pre-treatment performances of these methods were investigated. It was proven that the proposed model accurately predicted the efficiencies of ultrasonic pre-treatment methods.

Mechanism underlying the effect of combined therapy using glucosamine and low-dose cyclosporine A on the development of atopic dermatitis-like skin lesions in NC/Nga mice.

PubMed

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

2013-02-01

Combination therapy is often used in the treatment of atopic dermatitis (AD) to improve clinical efficacy or to spare the dose of each drug. Cyclosporine A (CsA) is a calcineurin inhibitor that was developed for the treatment of AD. Glucosamine (Glu) is a potent immunosuppressant that inhibits Th2-mediated immunity. We previously reported that Glu has an ameliorative effect on the development of the pathology in NC/Nga mice. The aims of our study were to investigate the therapeutic efficacy of combination of Glu and low-dose CsA 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 7 were used for treatment with Glu (500mg/kg) alone, low-dose CsA (2, 5, and 10mg/kg) or in combination. The clinical scores were reduced significantly by the combination treatment with Glu and low-dose CsA. The suppression of dermatitis by combined therapy was accompanied by decrease in the plasma level of IgE and in the splenic level of IL-4, IL-5, IL-13, TARC and eotaxin. Histological analysis of the skin also revealed that combination treatment significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Particularly, immunological evaluation reveals an increase of CD4(+)CD25(+) Treg cells in the combined treatment. The induction of TSLP, which leads to systemic Th2 response, was reduced in the skin on combination treatment. The protein expression of filaggrin and involucrin was recovered by combination treatment in the skin lesions, whereas the protein expression of keratin-10 and keratin-14 decreased in the combination treatment. Collectively, our findings suggest that combination treatment of Glu and low-dose CsA leads to the therapeutic effects in Df-induced AD-like skin lesion in NC/Nga mice through inhibition of IgE, inflammatory cellular infiltrate, and recovery of skin barrier function via a mechanism that may inhibition of Th2-mediated immune responses, in part, increment of CD4(+)CD25(+) Treg cells. These results suggest that this combined immunosuppressive treatment may provide important implications for the design of therapeutic strategies aimed at AD treatment. Copyright © 2013 Elsevier B.V. All rights reserved.

Degradation of lignin in birch sawdust treated by a novel Myrothecium verrucaria coupled with ultrasound assistance.

PubMed

Wang, Qing-Fang; Niu, Li-Li; Jiao, Jiao; Guo, Na; Zang, Yu-Ping; Gai, Qing-Yan; Fu, Yu-Jie

2017-11-01

Combined treatment of a novel fungal endophyte Myrothecium verrucaria coupled with ultrasound assistance was conducted to enhance lignin degradation in birch sawdust. The optimum treatment conditions were confirmed as the materials to liquid ratio 1:20, temperature 30°C, time 4days and pH 7, respectively. The results showed that the combined treatment led to the lignin degradation reaching 67.95±2.14%, while the lignin degradation were 45.50±2.12% and 13.75±0.66% with separate fungal treatment and ultrasound treatment, respectively. Moreover, SEM and FTIR analysis indicated that combined treatment significantly altered surface morphology and chemical structure of birch sawdust. The combined treatment greatly increased lignin removal during short time in mild environment. Therefore, these results demonstrated that the combined treatment of fungal endophyte coupled with ultrasound assistance has the high potential for the removal lignin in lignocellulose. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transient generation of hydrogen peroxide is responsible for carcinostatic effects of hydrogen combined with platinum nanocolloid, together with increases intracellular ROS, DNA cleavages, and proportion of G2/M-phase.

PubMed

Saitoh, Yasukazu; Ikeshima, Minoru; Kawasaki, Naho; Masumoto, Aoi; Miwa, Nobuhiko

2016-01-01

In our previous study, we demonstrated that combined treatment with hydrogen (H2) and platinum nanocolloid (Pt-nc) exerted markedly antiproliferative effects on cancer cells compared with each treatment alone. However, because the related mechanisms remain unclear, we investigated carcinostatic mechanisms of the combined treatment with H2 + Pt-nc. Significant suppression of cell proliferation was confirmed at 52 h following combined treatment, and the similar effect was also observed by the 30- or 40-min transient treatment with H2 + Pt-nc. The transient treatments led to changes in cell size and morphology, loss of microvilli, and apoptosis-like cell death at 120 h after treatment. Moreover, transient combined treatment with H2 + Pt-nc induced cell-cycle arrest, as reflected by decreased proportions of G1-phase cells and accumulation of G2/M-phase cells. In contrast, intracellular peroxide levels were temporarily and significantly increased immediately after H2 + Pt-nc treatment but not after treatment with H2 or Pt-nc alone. Additionally, combined treatment-induced carcinostatic effects were significantly diminished in the presence of catalase, and marked hydrogen peroxide (H2O2) generation was confirmed after mixing Pt-nc into cell culture media containing a high concentration of H2. These changes are in agreement with the results that carcinostatic effects were induced after only 40 min of treatment with H2 + Pt-nc. Thus, transient and marked generation of H2O2 is responsible for the carcinostatic effects of combined treatment with H2 + Pt-nc.

Controlled Trial of Very Low Calorie Diet, Behavior Therapy, and Their Combination in the Treatment of Obesity.

ERIC Educational Resources Information Center

Wadden, Thomas A; Stunkard, Albert J.

1986-01-01

Assessed the effectiveness of a combined program of very low calorie diet and behavior therapy in treating obesity. Combined treatment and behavior therapy alone subjects maintained weight losses; none of the diet alone subjects met the criterion used to define maintenance. Only those receiving behavior therapy alone and combined treatment showed…

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

PubMed

Wu, Xiaoyun; Xu, Yun

2015-05-01

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

Dapsone gel 5% in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer for the treatment of acne vulgaris: a 12-week, randomized, double-blind study.

PubMed

Fleischer, Alan B; Shalita, Alan; Eichenfield, Lawrence F; Abramovits, William; Lucky, Anne; Garrett, Steven

2010-01-01

To evaluate the safety and efficacy of dapsone gel 5% in the treatment of acne when used in combination with adapalene gel 0.1%, benzoyl peroxide gel 4% or moisturizer. This was a twelve-week, randomized, double-blind study. Patients aged 12 years and older (n=301) applied dapsone gel twice daily and were randomly assigned (1:1:1) to one of three additional treatments, applied once daily. By week 12, dapsone gel combined with any of the three additional treatments reduced the mean number of inflammatory lesions. However, the authors did not detect a significant difference in the reduction of inflammatory lesions when dapsone was used in combination with adapalene gel or with benzoyl peroxide gel compared to the dapsone plus moisturizer combination group (P=0.052 for both versus moisturizer combination). Patients treated with dapsone gel combined with adapalene showed a significantly better response in reduction in non-inflammatory and total acne lesion count than those who received the moisturizer combination. Local adverse reactions in all three treatment groups were minimal and generally mild in severity. Dapsone gel in combination with adapalene gel or benzoyl peroxide gel is safe and well tolerated for the treatment of acne vulgaris.

Combined treatment with MAO-A inhibitor and MAO-B inhibitor increases extracellular noradrenaline levels more than MAO-A inhibitor alone through increases in beta-phenylethylamine.

PubMed

Kitaichi, Yuji; Inoue, Takeshi; Nakagawa, Shin; Boku, Shuken; Izumi, Takeshi; Koyama, Tsukasa

2010-07-10

Monoamine oxidase inhibitors (MAO inhibitors) have been widely used as antidepressants. However, it remains unclear whether a difference exists between non-selective MAO inhibitors and selective MAO-A inhibitors in terms of their antidepressant effects. Using in vivo microdialysis methods, we measured extracellular noradrenaline and serotonin levels following administration of Ro 41-1049, a reversible MAO-A inhibitor and/or lazabemide, a reversible MAO-B inhibitor in the medial prefrontal cortex (mPFC) of rats. We examined the effect of local infusion of beta-phenylethylamine to the mPFC of rats on extracellular noradrenaline and serotonin levels. Furthermore, the concentrations of beta-phenylethylamine in the tissue of the mPFC after combined treatment with Ro 41-1049 and lazabemide were measured. The Ro 41-1049 alone and the combined treatment significantly increased extracellular noradrenaline levels compared with vehicle and lazabemide alone. Furthermore, the combined treatment increased noradrenaline levels significantly more than Ro 41-1049 alone did. The Ro 41-1049 alone and the combined treatment significantly increased extracellular serotonin levels compared with vehicle and lazabemide alone, but no difference in serotonin levels was found between the combined treatment group and the Ro 41-1049 group. Local infusion of low-dose beta-phenylethylamine increased extracellular noradrenaline levels, but not that of serotonin. Only the combined treatment significantly increased beta-phenylethylamine levels in tissues of the mPFC. Our results suggest that the combined treatment with a MAO-A inhibitor and a MAO-B inhibitor strengthens antidepressant effects because the combined treatment increases extracellular noradrenaline levels more than a MAO-A inhibitor alone through increases in beta-phenylethylamine. Copyright 2010 Elsevier B.V. All rights reserved.

[Effects of long-term localized fertilization on soil humus combining form in sheltered vegetable field].

PubMed

Zhang, Hongling; Liang, Chenghua; Du, Liyu; Chen, Xinzhi; Li, Jibai

2006-05-01

The study showed that on a sheltered vegetable field, a long-term application of organic plus chemical fertilizers induced a higher content of loosely combined soil humus than applying chemical fertilizers alone, while there was no significant difference in firmly combined humus content among different fertilization treatments. More tightly combined humus was observed in organic fertilizer treatments than in chemical fertilizer treatments, and the highest content (11.53 g x kg(-1)) was in the treatment of organic fertilizer plus chemical NPK. The ratio of loosely/tightly combined humus tended to decrease after a long-term application of organic fertilizer, being the lowest (1.10) in the treatment of organic fertilizer plus chemical NPK.

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.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bilder, Robert M.; Loo, Sandra; McGough, James J.; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del’Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T.

2016-01-01

Objective Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Method Children with ADHD (n = 182; age 7–14 years) completed an eight-week double blind randomized controlled trial with three arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A non-clinical comparison group (n = 93) had baseline testing, and a subset was re-tested 8 weeks later (n = 38). Analyses examined treatment effects in four cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. Results The ADHD group showed impaired working memory relative to the non-clinical comparison group (effect size = −0.53 SD units). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN, but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Conclusion Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone, and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear necessary to achieve normalization of cognitive function in ADHD. Clinical trial registration information Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273 PMID:27453080

Combining Motivational Interviewing with Cognitive-Behavioral Treatments for Substance Abuse: Lessons from the COMBINE Research Project

ERIC Educational Resources Information Center

Moyers, Theresa B.; Houck, Jon

2011-01-01

Motivational Interviewing began as a treatment for substance misuse and has strong empirical support as an intervention for these disorders. It is very common for MI to be combined with other types of treatment when it is used for substance abuse, and this article focuses on one example of this: the COMBINE Research Project. We examine the…

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.

The safety of ezetimibe and simvastatin combination for the treatment of hypercholesterolemia.

PubMed

Kei, Anastazia A; Filippatos, Theodosios D; Elisaf, Moses S

2016-01-01

In the light of the most recent and stricter dyslipidemia treatment guidelines, the need for combination hypolipidemic therapy is increasing. Ezetimibe plus simvastatin is available as a fixed dose therapy offering an efficient hypolipidemic treatment choice. Based on the positive results of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial, the use of this drug combination is expected to increase in the next years. This review discusses the current evidence regarding the safety of ezetimibe/simvastatin combination. Current evidence regarding possible associated side effects (musculoskeletal, gastrointestinal, endocrine, hematological, renal, ophthalmologic, allergic, malignancy) and drug interactions of this combination is thoroughly discussed. Ezetimibe and simvastatin treatment, either as a single pill or the combined use of the individual compounds, offers limited additional risk compared with simvastatin monotherapy and comprises a safe and efficient choice for dyslipidemia treatment in high-risk and diabetic patients.

Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats.

PubMed

Kitamura, Yoshihisa; Kanemoto, Erika; Sugimoto, Misaki; Machida, Ayumi; Nakamura, Yuka; Naito, Nanami; Kanzaki, Hirotaka; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki

2017-04-01

In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.

Improving Outcomes for Youth with ADHD: A Conceptual Framework for Combined Neurocognitive and Skill-Based Treatment Approaches

PubMed Central

Chacko, Anil; Kofler, Michael; Jarrett, Matthew

2014-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and chronic mental health condition that often results in substantial impairments throughout life. Although evidence-based pharmacological and psychosocial treatments exist for ADHD, effects of these treatments are acute, do not typically generalize into non-treated settings, rarely sustain over time, and insufficiently affect key areas of functional impairment (i.e., family, social, and academic functioning) and executive functioning. The limitations of current evidence-based treatments may be due to the inability of these treatments to address underlying neurocognitive deficits that are related to the symptoms of ADHD and associated areas of functional impairment. Although efforts have been made to directly target the underlying neurocognitive deficits of ADHD, extant neurocognitive interventions have shown limited efficacy, possibly due to misspecification of training targets and inadequate potency. We argue herein that despite these limitations, next-generation neurocognitive training programs that more precisely and potently target neurocognitive deficits may lead to optimal outcomes when used in combination with specific skill-based psychosocial treatments for ADHD. We discuss the rationale for such a combined treatment approach, prominent examples of this combined treatment approach for other mental health disorders, and potential combined treatment approaches for pediatric ADHD. Finally, we conclude with directions for future research necessary to develop a combined neurocognitive + skill-based treatment for youth with ADHD. PMID:25120200

Combined alkaline and ultrasonic pretreatment of sludge before aerobic digestion.

PubMed

Jin, Yiying; Li, Huan; Mahar, Rasool Bux; Wang, Zhiyu; Nie, Yongfeng

2009-01-01

Alkaline and ultrasonic sludge disintegration can be used as the pretreatment of waste activated sludge (WAS) to promote the subsequent anaerobic or aerobic digestion. In this study, different combinations of these two methods were investigated. The evaluation was based on the quantity of soluble chemical oxygen demand (SCOD) in the pretreated sludge as well as the degradation of organic matter in the subsequent aerobic digestion. For WAS samples with combined pretreatment, the released COD levels were higher than those with ultrasonic or alkaline pretreatment alone. When combined with the ultrasonic treatment, NaOH treatment was more efficient than Ca(OH)2 for WAS solubilization. The COD levels released in various sequential options of combined NaOH and ultrasonic treatments were in the the following descending order: simultaneous treatment > NaOH treatment followed by ultrasonic treatment > ultrasonic treatment followed by NaOH treatment. For simultaneous treatment, low NaOH dosage (100 g/kg dry solid), short duration (30 min) of NaOH treatment, and low ultrasonic specific energy (7500 kJ/kg dry solid) were suitable for sludge disintegration. Using combined NaOH and ultrasonic pretreatment with optimal parameters, the degradation efficiency of organic matter was increased from 38.0% to 50.7%, which is much higher than that with ultrasonic (42.5%) or with NaOH pretreatment (43.5%) in the subsequent aerobic digestion at the same retention time.

Safety assessment of combination therapies in the treatment of obesity: focus on naltrexone/bupropion extended release and phentermine-topiramate extended release.

PubMed

Halpern, Bruno; Mancini, Marcio C

2017-01-01

Few studies on combination therapies for the treatment of obesity had been conducted until recently, when two fixed-dose combinations, bupropion-naltrexone ER fixed-dose combination and phentermine-topiramate ER titrated-dose combinations were evaluated in clinical studies that ultimately led to FDA approval. Areas covered: In this review, we discuss safety concerns about both combinations, the rationale and history of combination therapies for obesity (including phentermine plus fenfluramine), and possible future new combinations. Expert opinion: Combination therapies are a promising new area in obesity treatment, similar to what occurs with diabetes and hypertension. Safety assessment is highly important due to the high number of potential users on a chronic basis.

Neural and behavioural changes in male periadolescent mice after prolonged nicotine-MDMA treatment.

PubMed

Adeniyi, Philip A; Ishola, Azeez O; Laoye, Babafemi J; Olatunji, Babawale P; Bankole, Oluwamolakun O; Shallie, Philemon D; Ogundele, Olalekan M

2016-02-01

The interaction between MDMA and Nicotine affects multiple brain centres and neurotransmitter systems (serotonin, dopamine and glutamate) involved in motor coordination and cognition. In this study, we have elucidated the effect of prolonged (10 days) MDMA, Nicotine and a combined Nicotine-MDMA treatment on motor-cognitive neural functions. In addition, we have shown the correlation between the observed behavioural change and neural structural changes induced by these treatments in BALB/c mice. We observed that MDMA (2 mg/Kg body weight; subcutaneous) induced a decline in motor function, while Nicotine (2 mg/Kg body weight; subcutaneous) improved motor function in male periadolescent mice. In combined treatment, Nicotine reduced the motor function decline observed in MDMA treatment, thus no significant change in motor function for the combined treatment versus the control. Nicotine or MDMA treatment reduced memory function and altered hippocampal structure. Similarly, a combined Nicotine-MDMA treatment reduced memory function when compared with the control. Ultimately, the metabolic and structural changes in these neural systems were seen to vary for the various forms of treatment. It is noteworthy to mention that a combined treatment increased the rate of lipid peroxidation in brain tissue.

Synergistic Antiproliferative Effects of Combined γ-Tocotrienol and PPARγ Antagonist Treatment Are Mediated through PPARγ-Independent Mechanisms in Breast Cancer Cells

PubMed Central

Sylvester, Paul W.

2014-01-01

Previous findings showed that the anticancer effects of combined γ-tocotrienol and peroxisome proliferator activated receptor γ (PPARγ) antagonist treatment caused a large reduction in PPARγ expression. However, other studies suggest that the antiproliferative effects of γ-tocotrienol and/or PPARγ antagonists are mediated, at least in part, through PPARγ-independent mechanism(s). Studies were conducted to characterize the role of PPARγ in mediating the effects of combined treatment of γ-tocotrienol with PPARγ agonists or antagonists on the growth of PPARγ negative +SA mammary cells and PPARγ-positive and PPARγ-silenced MCF-7 and MDA-MB-231 breast cancer cells. Combined treatment of γ-tocotrienol with PPARγ antagonist decreased, while combined treatment of γ-tocotrienol with PPARγ agonist increased, growth of all cancer cells. However, treatment with high doses of 15d-PGJ2, an endogenous natural ligand for PPARγ, had no effect on cancer cell growth. Western blot and qRT-PCR studies showed that the growth inhibitory effects of combined γ-tocotrienol and PPARγ antagonist treatment decreased cyclooxygenase (COX-2), prostaglandin synthase (PGDS), and prostaglandin D2 (PGD2) synthesis. In conclusion, the anticancer effects of combined γ-tocotrienol and PPARγ antagonists treatment in PPARγ negative/silenced breast cancer cells are mediated through PPARγ-independent mechanisms that are associated with a downregulation in COX-2, PGDS, and PGD2 synthesis. PMID:24729783

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

PubMed

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

2015-03-01

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

Killing effects of Huaier Granule combined with DC-CIK on nude mice transplanted with colon carcinoma cell line.

PubMed

Sun, Wen-Wen; Dou, Jin-Xia; Zhang, Lin; Qiao, Li-Kui; Shen, Na; Zhao, Qiang; Gao, Wen-Yuan

2017-07-11

This study aims to compare the efficacy of different treatments for nude mice transplanted with HT-29 colon carcinoma cell line. BalB/C nude mice were transplanted with HT-29 colon carcinoma cell line and randomly divided into four groups, with 5 mice in each group: blank control group, DC-CIK group, Huaier Granule group, and Huaier Granule group combined with DC-CIK group (combined treatment group). For DC-CIK group and combined treatment group, 1×106 DC-CIK cells were injected via the tail vein 4 days after transplantation. The injection was performed twice weekly for a total of 2 weeks. For Huaier Granule group and combined treatment group, Huaier Granule was administered at the dose of 20 g/60 g, by dissolving 20 g of Huaier granules in 600 ml of pure water. Intragastric administration of 0.2 ml of granules was performed once daily for 3 weeks. For the blank control group, equal volume of normal saline was given. Tumor size and body weight of nude mice were measured every 2 days during the 3-week treatment. The mice were sacrificed at the end of treatment to harvest tumors. Key genes of the signaling pathway were detected by RT-PCR. At the end of treatment, mice in combined treatment group, DC-CIK group and Huaier Granule group remained stable emotionally with normal mobility and water and food intake. However, in the blank control group, the mobility was restricted starting from the third week and the mice were on the verge of dying. The expression of PI3KR1, Akt, Wnt1, CTTNB1, Notch1, Notch2 and Notch3 genes were all downregulated significantly in the combined treatment group compared with DC-CIK group and Huaier Granule group (P<0.05). Therefore, the combined treatment of Huaier Granule combined with DC-CIK achieved the best effect in nude mice transplanted with HT-29 colon carcinoma cell line.

[Combined orthodontic-orthoganthic surgery to treat asymmetric mandibular excess malocclusions].

PubMed

Li, Xiao-Bing; Chen, Song; Chen, Yang-Xi; Li, Jun

2005-06-01

To discuss the skeletal and dentoalveolar characteristics of asymmetric mandibular excess malocclusions and to discuss the procedures of combined orthodontic-orthonganthic surgery treatments of asymmetric mandibular excess malocclusions. 25 cases treated by combined orthodontic-orthognathic surgery treatments were reviewed to find out the specialties of this kind of therapy. The asymmetric of mandible presents anterior and posterior teeth tipped both sagitally and horizontally, as well as upper and lower jaws incompatibility. The pre-surgical orthodontic treatments included decomposition of anterior and posterior teeth, leveling and aligning the teeth etc. The post-surgical orthodontic treatments were to detail the occlusions. The patients all got functional and aesthetic good results after the combined orthodontic-orthognathic surgery treatments. The asymmetric mandibular excess affects the harmony of the face badly, and the correction of it must be carried out by the combined orthodontic-orthognathic surgery treatments. The pre- and post-surgical orthodontic treatments are the key stages to make the skeletal corrections stable.

Imagery rescripting versus in vivo exposure in the treatment of snake fear.

PubMed

Hunt, Melissa; Fenton, Miriam

2007-12-01

This study compared imagery rescripting, in vivo exposure therapy and their combination in the treatment of snake fear. Imaginal ability was assessed pre-treatment, and was correlated with baseline avoidance. Snake fearful individuals were randomly assigned to cognitive therapy involving imagery rescripting, in vivo exposure, a combination of the two, or a relaxation control. All active treatment groups improved significantly more than the control group in both fearfulness and behavioral approach. There were no significant differences between the active treatment groups, although the combined treatment tended to be slightly more efficacious.

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.

Individual patient data meta-analysis of combined treatments versus psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for adult depression: a protocol.

PubMed

Weitz, Erica; Kleiboer, Annet; van Straten, Annemieke; Hollon, Steven D; Cuijpers, Pim

2017-02-13

There are many proven treatments (psychotherapy, pharmacotherapy or their combination) for the treatment of depression. Although there is growing evidence for the effectiveness of combination treatment (psychotherapy + pharmacotherapy) over pharmacotherapy alone, psychotherapy alone or psychotherapy plus pill placebo, for depression, little is known about which specific groups of patients may respond best to combined treatment versus monotherapy. Conventional meta-analyses techniques have limitations when tasked with examining whether specific individual characteristics moderate the effect of treatment on depression. Therefore, this protocol outlines an individual patient data (IPD) meta-analysis to explore which patients, with which clinical characteristics, have better outcomes in combined treatment compared with psychotherapy (alone or with pill placebo), pharmacotherapy and pill placebo. Study searches are completed using an established database of randomised controlled trials (RCTs) on the psychological treatment of adult depression that has previously been reported. Searches were conducted in PubMed, PsycInfo, Embase and the Cochrane Central Register of Controlled Trials. RCTs comparing combination treatment (psychotherapy + pharmacotherapy) with psychotherapy (with or without pill placebo), pharmacotherapy or pill placebo for the treatment of adult depression will be included. Study authors of eligible trials will be contacted and asked to contribute IPD. Conventional meta-analysis techniques will be used to examine differences between studies that have contributed data and those that did not. Then, IPD will be harmonised and analysis using multilevel regression will be conducted to examine effect moderators of treatment outcomes. Study results outlined above will be published in peer-reviewed journals. Study results will contribute to better understanding whether certain patients respond best to combined treatment or other depression treatments and provide new information on moderators of treatment outcome that can be used by patients, clinicians and researchers. CRD42016039028. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

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

PubMed

Mei, Xue-Ling; Wang, Li

2018-01-01

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

Methodologies in the modeling of combined chemo-radiation treatments

NASA Astrophysics Data System (ADS)

Grassberger, C.; Paganetti, H.

2016-11-01

The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

[Killing effect of Huaier combined with DC-CIK on nude mice bearing colon cancer HT29 stem cells in vivo].

PubMed

Sun, Wen-Wen; Dou, Jin-Xia; Zhang, Lin; Qiao, Li-Kui; Shen, Na; Gao, Wen-Yuan

2018-01-01

To compare the therapeutic effects of different treatment methods on the nude mice bearing colon cancer HT29 cells. BalB/C nude mice colon cancer stem cell models were established and randomly divided into the following four groups, with 8 nude mice in each group: blank control group, DC-CIK group, Huaier group, and Huaier combined with DC-CIK group (combined treatment group). The mice in DC-CIK group and combined treatment group received 1×10⁶ DC-CIK cells treatment by tail vein injectionafter the tumor stem cells were inoculated for 4 days,2 times a week for three weeks. The mice in Huaier group and combined treatment group received intragastric administration at the dose of 20 g/60 kg body weight, 0.2 mL/time, once a day for a total of three weeks. The mice in control group received equal volume of normal saline. Tumor size and body weight of nude mice were measured every 2 days during treatment for three weeks in each group. After the treatment, the nude mice were sacrificed to measure the tumor weight and the tumor inhibition rate was calculated. The RT-PCR method was used to detect the expression levels of the key genes in the signal pathway. After the end of the treatment, the quality of the tumor in the Huaier group, DC-CIK group and combined treatment group was significantly lower than that in the control group; the quality in combined treatment group was significantly lower than that in Huaier group and DC-CIK group.Among them, the tumor inhibition rate reached 46.77% in the combined treatment group. In respect of changes in expression levels of key genes in the signaling pathway, the mRNA expression levels of key genes PI3KR1 and Akt in PI3K/Akt pathway, key genes Wnt1 and CTTNB1 in Wnt/ β -catenin pathway, and key genes Notch1, Notch2, Notch3 in Notch pathway in the combined treatment group were lower than those in DC-CIK group and Huaier group. The Huaier combined with DC-CIK group showed best therapeutic effect among different treatment methods for HT29 stemcell colon tumors in nude mice, providing a new idea for clinical treatment of colon cancer. Copyright© by the Chinese Pharmaceutical Association.

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

PubMed Central

Stoops, William W.; Rush, Craig R.

2014-01-01

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

Combined free nitrous acid and hydrogen peroxide pre-treatment of waste activated sludge enhances methane production via organic molecule breakdown

PubMed Central

Zhang, Tingting; Wang, Qilin; Ye, Liu; Batstone, Damien; Yuan, Zhiguo

2015-01-01

This study presents a novel pre-treatment strategy using combined free nitrous acid (FNA i.e. HNO2) and hydrogen peroxide (H2O2) to enhance methane production from WAS, with the mechanisms investigated bio-molecularly. WAS from a full-scale plant was treated with FNA alone (1.54 mg N/L), H2O2 alone (10–80 mg/g TS), and their combinations followed by biochemical methane potential tests. Combined FNA and H2O2 pre-treatment substantially enhanced methane potential of WAS by 59–83%, compared to 13–23% and 56% with H2O2 pre-treatment alone and FNA pre-treatment alone respectively. Model-based analysis indicated the increased methane potential was mainly associated with up to 163% increase in rapidly biodegradable fraction with combined pre-treatment. The molecular weight distribution and chemical structure analyses revealed the breakdown of soluble macromolecules with the combined pre-treatment caused by the deamination and oxidation of the typical functional groups in proteins, polysaccharides and phosphodiesters. These changes likely improved the biodegradability of WAS. PMID:26565653

Nicotine Gum and Behavioral Treatment in Smoking Cessation.

ERIC Educational Resources Information Center

Hall, Sharon M.; And Others

1985-01-01

Assigned 120 smoking cessation subjects to either intensive behavioral treatment, nicotine gum in low-contact treatment, or to combined treatment. Combined treatment produced higher abstinence rates than other conditions at all assessments. Differences were significant at 3, 12, and 26 weeks, but not at 52 weeks. (NRB)

Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2

PubMed Central

Tan, Lei; Hou, Zhongyu; Gao, Yanzhi

2018-01-01

The objective of this study was to investigate the efficacy of combined treatment with vacuum sealing drainage (VSD) and recombinant human epidermal growth factor (rhEGF) for refractory wounds in the extremities, and its effect on serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-2. Ninety-eight patients with refractory wounds in the extremities were recruited and randomly divided into the combined treatment group (underwent VSD and rhEGF treatment) and control group (underwent VSD only) with 49 cases each. Formation of granulation tissue on the wound surface was assessed and scored. The wound healing rate was calculated after 1 week of treatment, and the time of complete healing was recorded. Serum levels of IL-6, IL-2, and TNF-α were measured using enzyme-linked immunosorbent assay. After 1 week of treatment, granulation tissue formation on wound surfaces was significantly improved (p<0.05) compared with that before treatment in both groups. Moreover, granulation tissue formation on wound surfaces was superior in the combined treatment group than in the control group (p<0.05). The wound healing rate was 63.50±4.75% in the combined treatment group and 31.79±3.52% in the control group, and the difference was statistically significant (p<0.05). The time of complete healing was 15.11±2.24 days in the combined treatment group and 19.63±2.76 days in the control group, and the difference was statistically significant (p<0.05). The serum levels of IL-6, IL-2, and TNF-α, in the two groups were significantly lower than those before treatment (p<0.05). Moreover, the levels in the combined treatment group were significantly lower than those in the control group (p<0.05). In conclusion, combined treatment with VSD and rhEGF reduced inflammation and shortened the time of complete healing of refractory wounds in the extremities. Measurement of the levels of related inflammatory factors provided a reference for the prognosis of refractory wounds. PMID:29250151

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

PubMed Central

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

2014-01-01

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

Combined pulsed dye and CO2 lasers in the treatment of angiolymphoid hyperplasia with eosinophilia.

PubMed

Sagi, Lior; Halachmi, Shlomit; Levi, Assi; Amitai, Dan Ben; Enk, Claes D; Lapidoth, Moshe

2016-08-01

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon dermatosis of unknown etiology that manifests as characteristic red nodules and papules with a predilection for the scalp and periauricular region. Treatment is required for both esthetic and functional reasons, as lesions may ulcerate and bleed. Many treatment approaches have been reported, including excision, systemic medical approaches, topical or intralesional therapies, and non-invasive modalities including cryotherapy, electrosurgery, and laser. Treatments have exhibited variable efficacy, and the recurrence rate is 100 %. We report the combination of pulsed dye laser and CO2 laser in the treatment of ALHE in 14 patients. All patients exhibited clinical response after a mean of 2.4 ± 0.4 treatment sessions. The clinical efficacy of the combined treatment, together with its well-tolerated nature, render the use of pulsed dye laser in combination with CO2 laser, a viable treatment for debulking ALHE lesions. Ongoing maintenance treatments are needed to due to the high degree of relapse.

Pilot Cases of Combined Cognitive Processing Therapy and Smoking Cessation for Smokers With Posttraumatic Stress Disorder.

PubMed

Dedert, Eric A; Resick, Patricia A; McFall, Miles E; Dennis, Paul A; Olsen, Maren; Beckham, Jean C

2016-01-01

Posttraumatic stress disorder (PTSD) and smoking are often comorbid, and both problems are in need of improved access to evidence-based treatment. The combined approach could address two high-priority problems and increase patient access to both treatments, but research is needed to determine whether this is feasible and has promise for addressing both PTSD and smoking. We collected data from 15 test cases that received a treatment combining two evidence-based treatments: cognitive processing therapy-cognitive version (CPT-C) for PTSD and integrated care for smoking cessation (ICSC). We explored two combined treatment protocols including a brief (six-session) CPT-C with five follow-up in-person sessions focused on smoking cessation (n=9) and a full 12-session CPT-C protocol with ICSC (n=6). The combined interventions were feasible and acceptable to patients with PTSD making a quit attempt. Initial positive benefits of the combined treatments were observed. The six-session dose of CPT-C and smoking cessation resulted in 6-month bioverified smoking abstinence in two of nine participants, with clinically meaningful PTSD symptom reduction in three of nine participants. In the second cohort (full CPT-C and smoking treatment), both smoking and PTSD symptoms were improved, with three of six participants abstinent from smoking and four of six participants reporting clinically meaningful reduction in PTSD symptoms. Results suggested that individuals with PTSD who smoke are willing to engage in concurrent treatment of these problems and that combined treatment is feasible. Copyright © 2015. Published by Elsevier Ltd.

[Diuretics in monotherapy and in combination with other diuretics and nondiuretics in the treatment of hypertension].

PubMed

Spinar, J; Spinarová, L; Vítovec, J

2013-06-01

Diuretics belong to the basic group of medicines for the treatment of hypertension and heart failure. In the case of hypertension treatment, their main indication is higher age and isolated systolic hypertension. In the case of heart failure they are used for the treatment of swellings and shortness of breath. The most frequently prescribed group of diuretics is thiazides and similar products. In patients with renal insufficiency, loop diuretics are administered. In the case of hypertension, diuretics are mainly used in the combination treatment. The most frequently used diuretic in combination is again hydrochlorothiazide, which is combined with reninangiotensin system blockers. It is mainly the combination of an ACE inhibitor + indapamide that seems to be modern and promising, and it is, on the basis of large clinical trials, recommended also for diabetics (ADVANCE) or for secondary prevention following a cerebrovascular accident (PROGRESS) or for the elderly (HYVET). Also a combination of two diuretics is popular -  mainly hydrochlorothiazide + amiloride. A combination of a betablocker and diuretic is less suitable.

Farnesylthiosalicylic acid sensitizes hepatocarcinoma cells to artemisinin derivatives

PubMed Central

Wu, Liping; Pang, Yilin; Qin, Guiqi; Xi, Gaina; Wu, Shengnan; Wang, Xiaoping; Chen, Tongsheng

2017-01-01

Dihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor, in HCC cells (Huh-7 and HepG2 cell lines). FTS pretreatment significantly enhanced DHA/ARS-induced phosphatidylserine (PS) externalization, Bak/Bax activation, mitochondrial membrane depolarization, cytochrome c release, and caspase-8 and -9 activations, characteristics of the extrinsic and intrinsic apoptosis. Pretreatment with Z-IETD-FMK (caspase-8 inhibitor) potently prevented the cytotoxicity of the combination treatment of DHA/ARS and FTS, and pretreatment with Z-VAD-FMK (pan-caspase inhibitor) significantly inhibited the loss of ΔΨm induced by DHA/ARS treatment or the combination treatment of DHA/ARS and FTS in HCC cells. Furthermore, silencing Bak/Bax modestly but significantly inhibited the cytotoxicity of the combination treatment of DHA/ARS and FTS. Interestingly, pretreatment with an antioxidant N-Acetyle-Cysteine (NAC) significantly prevented the cytotoxicity of the combination treatment of DHA and FTS instead of the combination treatment of ARS and FTS, suggesting that reactive oxygen species (ROS) played a key role in the anticancer action of the combination treatment of DHA and FTS. Similar to FTS, DHA/ARS also significantly prevented Ras activation. Collectively, our data demonstrate that FTS potently sensitizes Huh-7 and HepG2 cells to artemisinin derivatives via accelerating the extrinsic and intrinsic apoptotic pathways. PMID:28182780

Combination treatment with excimer laser and narrowband UVB light in vitiligo patients.

PubMed

Shin, Sungsik; Hann, Seung-Kyung; Oh, Sang Ho

2016-01-01

For the treatment of vitiligo, narrowband UVB (NBUVB) light is considered the most effective for nonsegmental vitiligo, while excimer laser treatment is commonly used for localized vitiligo. However, treatment areas may potentially be missed with excimer laser treatment. We aimed to evaluate the effect of combinational treatment with NBUVB light and excimer laser on vitiligo. All patients were first treated with NBUVB; excimer laser was then applied in conjunction with NBUVB phototherapy due to a slow response or no further improvement with continuous NBUVB treatment alone. To minimize adverse effects, a fixed dose of NBUVB was administered, and the dose of excimer laser was increased based on patient response. Among 80 patients, 54 patients showed responses after combination with excimer laser; however, 26 patients (32.5%) showed no remarkable change after combination therapy. Of the 26 patients who showed no further response, 12 patients (46.1%) presented with vitiligo on the acral areas, which are known to the least responsive sites. Our study suggests that combined treatment of NBUVB and excimer laser in vitiligo may enhance the treatment response without remarkable side effects, therefore might also increase the compliance of the patients to the treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neuroinflammatory and cognitive consequences of combined radiation and immunotherapy in a novel preclinical model

PubMed Central

McGinnis, Gwendolyn J.; Friedman, David; Young, Kristina H.; Torres, Eileen Ruth S.; Thomas, Charles R.; Gough, Michael J.; Raber, Jacob

2017-01-01

Background Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments. Currently, gaps exist as to whether these treatments impact the brain in individuals with or without tumors and with regard to the underlying mechanisms. Results Combined treatment with precision RT and checkpoint inhibitor IT achieved control of tumor growth. However, BALB/c mice receiving combined treatment demonstrated changes in measures of anxiety levels, regardless of tumor status. C57BL/6J mice with tumors demonstrated increased anxiety, except following combined treatment. Object recognition memory was impaired in C57BL/6J mice without tumors following combined treatment. All mice with tumors showed impaired object recognition, except those treated with RT alone. Mice with tumors demonstrated impaired amygdala-dependent cued fear memory, while maintaining hippocampus-dependent context fear memory. These behavioral alterations and cognitive impairments were accompanied by increased microglial activation in mice receiving immunotherapy alone or combined with RT. Finally, based on tumor status, there were significant changes in proinflammatory cytokines (IFN-γ, IL-6, IL-5, IL-2, IL-10) and a growth factor (FGF-basic). Materials and Methods Here we test the hypothesis that IT combined with peripheral RT have detrimental behavioral and cognitive effects as a result of an enhanced proinflammatory environment in the brain. BALB/c mice with or without injected hind flank CT26 colorectal carcinoma or C57BL/6J mice with or without Lewis Lung carcinoma were used for all experiments. Checkpoint inhibitor IT, using an anti-CTLA-4 antibody, and precision CT-guided peripheral RT alone and combined were used to closely model clinical treatment. We assessed behavioral and cognitive performance and investigated the immune environment using immunohistochemistry and multiplex assays to analyze proinflammatory mediators. Conclusions Although combined treatment achieved tumor growth control, it affected the brain and induced changes in measures of anxiety, cognitive impairments, and neuroinflammation. PMID:27893434

Ceftazidime-avibactam: novel antimicrobial combination for the treatment of complicated urinary tract infections.

PubMed

Alidjanov, Jakhongir F; Fritzenwanker, Moritz; Hoffman, Ivan; Wagenlehner, Florian M

2017-06-01

Ceftazidime-avibactam is a combination of a third-generation cephalosporin and a novel non-beta-lactam beta-lactamase inhibitor. This combination was recently recommended for the treatment of complicated urinary tract infections, including acute pyelonephritis, in adults with limited or no alternative treatment options. The current review is aimed to determine activity, efficacy and safety of ceftazidime-avibactam in the treatment of patients with complicated urinary tract infections.

[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.

[Treatment of combined hyperlipidemia patients by jiangzhi tongluo soft capsule combined atorvastatin calcium tablet: a clinical study].

PubMed

Xie, Ying; He, Yu-Bin; Zhang, Shi-Xin; Pan, Ai-Qun; Zhang, Jun; Guan, Xiao-Hong; Wang, Jin-Xue; Guo, Wen-Sheng

2014-09-01

To evaluate the efficacy and safety of using Jiangzhi Tongluo Soft Capsule (JTSC) combined with Atorvastatin Calcium Tablet (ACT) or ACT alone in treatment of combined hyperlipidemia. A randomized, double blinded, parallel control, and multi-center clinical research design was adopted. Totally 138 combined hyperlipidemia patients were randomly assigned to the combined treatment group (A) and the atorvastatin treatment group (B) by random digit table, 69 in each group. All patients took ACT 20 mg per day. Patients in the A group took JTSC 100 mg each time, 3 times per day. Those in the B group took JTSC simulated agent, 100 mg each time, 3 times per day. The treatment period for all was 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were observed before treatment, at week 4 and 8 after treatment; and safety was assessed as well. At week 4 and 8 after treatment serum TG decreased by 26.69% and 33.29% respectively in the A group (both P < 0.01), while it was decreased by 25.7% and 22.98% respectively in the B group (both P < 0.01). At week 8 decreased serum TG was obviously higher in the A group than in the B group (P < 0.05). Compared with before treatment, serum levels of LDL-C and TC levels decreased significantly in the two groups (all P < 0.01). There was no statistical difference in the drop-out value and the drop-out rate of serum LDL-C and TC levels (P > 0.05). At week 8 the serum HDL-C level showed an increasing tendency in the two groups. No obvious increase in peptase or creatase occurred in the two groups after treatment. JTSC combined with ACT could lower the serum TG level of combined hyperlipidemia patients with safety.

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome.

PubMed

AlSarheed, Maha A; Al-Sehaibany, Fares S

2015-08-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan.

Combined orthodontic and periodontic treatment in a child with Papillon Lefèvre syndrome

PubMed Central

AlSarheed, Maha A.; Al-Sehaibany, Fares S.

2015-01-01

A 9-year-old girl with Papillon-Lefèvre syndrome (PLS) was treated orthodontically 24 months after the start of mechanical and antibiotic therapy in adjunct with periodontal treatment every 6 weeks. After achieving stable periodontal conditions, orthodontic treatment was commenced to correct the teeth position, facial profile, and maxillary protraction. Following the combination therapy and a failure to detect Actinobacillus actinomycetemcomitans from any site in the oral cavity, orthodontic treatment with a fixed appliance was performed aside from creating space for eruption of permanent teeth. We found that combined periodontal and orthodontic treatment of PLS may be successful with a complex interdisciplinary regimen and close follow up. This is a 2-year follow-up case report of a girl with PLS. Orthodontic and periodontic therapy were offered using combined treatments of orthodontic and periodontal with the benefit of prosthodontic consultation, resulting in a treatment plan. PMID:26219452

Properties and microstructures for dual alloy combinations of three superalloys with alloy 901

NASA Technical Reports Server (NTRS)

Harf, F. H.

1985-01-01

Dual alloy combinations have potential for use in aircraft engine components such as turbine disks where a wide range of stress and temperature regimes exists during operation. Such alloy combinations may directly result in the conservation of elements which are costly or not available domestically. Preferably, a uniform heat treatment yielding good properties for both alloys should be used. Dual alloy combinations of iron rich Alloy 901 with nickel base superalloys Rene 95, Astroloy, or MERL 76 were not isostatically pressed from prealloyed powders. Individual alloys, alloy mixtures, and layered alloy combinations were given the heat treatments specified for their use in turbine disks or appropriate for Alloy 901. Selected specimens were overaged for 1500 hr at 650 C. Metallographic examinations revealed the absence of phases not originally present in either alloy of a combination. Mechanical tests showed adequate properties in combinations of Rene 95 or Astroloy with Alloy 901 when given the Alloy 901 heat treatment. Combinations with MERL 76 had better properties when given the MERL 76 heat treatment. The results indicate that these combinations are promising candidates for use in turbine disks.

Trazodone Addition to Paroxetine and Mirtazapine in a Patient with Treatment-Resistant Depression: The Pros and Cons of Combining Three Antidepressants

PubMed Central

Alves, José Carlos; Rego, Raquel Garcia

2016-01-01

Dual antidepressant combination for treatment-resistant depression is a strategy well supported by literature and accepted in clinical practice. Rather, the usefulness of the combination of more than two antidepressants is controversial. This may be related to the possibility of higher side-effect burden and to doubts about its pharmacological effectiveness and therapeutic advantage compared to other standard treatment options. We report a relapse of moderate-to-severe depressive symptoms with insomnia that successfully remitted after the addition of trazodone to a dual combination of paroxetine and mirtazapine (in standard effective doses) in a patient with treatment-resistant depression. We also review the literature and discuss the utility of triple antidepressant combination in treatment-resistant depression. This clinical case highlights the utility of combining trazodone as a third antidepressant for the relapse of depressive symptoms after the failure of a dual antidepressant combination. Trazodone may be advantageous in patients presenting recurrence of moderate-to-severe depressive symptoms that include sleep problems and/or insomnia and may be particularly useful when benzodiazepines are not recommended. Although its use may be controversial and associated with higher risk of side-effects, more investigation is needed to determine the efficacy and safety for triple antidepressant combinations as reliable strategies for treatment-resistant depression in clinical practice. PMID:27807450

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.

PubMed

Bilder, Robert M; Loo, Sandra K; McGough, James J; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del'Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T

2016-08-01

Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD. Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-12-01

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

Influence of dimethyl dicarbonate on the resistance of Escherichia coli to a combined UV-Heat treatment in apple juice

PubMed Central

Gouma, Maria; Gayán, Elisa; Raso, Javier; Condón, Santiago; Álvarez, Ignacio

2015-01-01

Commercial apple juice inoculated with Escherichia coli was treated with UV-C, heat (55°C) and dimethyl dicarbonate – DMDC (25, 50, and 75 mg/L)-, applied separately and in combination, in order to investigate the possibility of synergistic lethal effects. The inactivation levels resulting from each treatment applied individually for a maximum treatment time of 3.58 min were limited, reaching 1.2, 2.9, and 0.06 log10 reductions for UV, heat, and DMDC (75 mg/L), respectively. However, all the investigated combinations resulted in a synergistic lethal effect, reducing the total treatment time and UV dose, with the synergistic lethal effect being higher when larger concentrations of DMDC were added to the apple juice. The addition of 75 mg/L of DMDC prior to the combined UV-C light treatment at 55°C resulted in 5 log10 reductions after only 1.8 min, reducing the treatment time and UV dose of the combined UV-Heat treatment by 44%. PMID:26042117

Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

PubMed

Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

2016-06-01

Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

A comparative, epidemiological study of acute renal colic presentations to emergency departments in Doha, Qatar, and Melbourne, Australia.

PubMed

Pathan, Sameer A; Mitra, Biswadev; Bhutta, Zain A; Qureshi, Isma; Spencer, Elle; Hameed, Asmaa A; Nadeem, Sana; Tahir, Ramsha; Anjum, Shahzad; Cameron, Peter A

2018-01-03

This study aimed to compare the epidemiology, clinical presentations, management, and outcomes of renal colic presentations in two major academic centers from geographically diverse populations: Qatar (a country in the Afro-Asian stone belt) and South-Eastern Australia (not within a stone belt). We undertook a retrospective cohort study of patients with renal colic who presented to the Hamad General Hospital Emergency Department (HGH-ED), Qatar, and The Alfred ED, Melbourne, Australia, during a period of 1 year from August 1, 2012, to July 31, 2013. Cases were identified using ICD-9-CM codes, and an electronic template was used to record the data on predefined clinical variables. A total of 12,223 from the HGH-ED and 384 from The Alfred ED were identified as renal colic presentations during the study period. The rate of renal colic presentations at the HGH-ED was 27.9 per 1000 ED visits compared to 6.7 per 1000 ED visits at The Alfred ED. Patients presenting to the HGH-ED were significantly younger [34.9 years (29.0-43.4) than The Alfred ED [48 years (37-60); P < 0.001]. The median stone size was larger in the HGH-ED group [6 (4-8) mm] versus The Alfred ED group [4 (3-6) mm, P < 0.001]. The intervention rate in the stone-positive population was significantly higher in the HGH-ED group as opposed to The Alfred ED group (38.7 versus 11.9%, P < 0.001). At the time of discharge, The Alfred ED group received fewer analgesic prescriptions (55.8 versus 83.5%, P < 0.001) and more tamsulosin prescriptions (25.3 versus 11.7%, P < 0.001). Renal colic presentations to the HGH-ED, Qatar, were younger, with larger stone size mostly located in the lower ureter, compared to The Alfred ED, Melbourne, Australia. The findings suggest that the benefits of treatment including medical expulsion therapy will vary between the two populations. Differences in epidemiology and patient mix should be considered while tailoring strategies for effective management of patients with renal colic in a given setting.

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.

Mineralocorticoid receptor blockade in addition to angiotensin converting enzyme inhibitor or angiotensin II receptor blocker treatment: an emerging paradigm in diabetic nephropathy: a systematic review.

PubMed

Mavrakanas, Thomas A; Gariani, Karim; Martin, Pierre-Yves

2014-02-01

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard therapeutic intervention in diabetic patients with chronic kidney disease (CKD). Concomitant mineralocorticoid receptor blockade has been studied as a novel approach to further slow down CKD progression. We used PubMed and EMBASE databases to search for relevant literature. We included in our review eight studies in patients of at least 18 years of age, with a diagnosis of type 1 or type 2 diabetes mellitus and diabetic nephropathy, under an angiotensin converting enzyme inhibitor (ACEI) and/or an angiotensin II receptor blocker (ARB) as standard treatment. A subset of patients in each study also received a mineralocorticoid receptor blocker (MRB) (either spironolactone or eplerenone) in addition to standard treatment. Combined treatment with a mineralocorticoid receptor blocker further reduced albuminuria by 23 to 61% compared with standard treatment. Estimated glomerular filtration rate values upon study completion slightly decreased under combined treatment. Blood pressure levels upon study completion were significantly lower with combined treatment in three studies. Hyperkalemia prevalence increased in patients under combined treatment raising dropout rate up to 17%. Therefore, combined treatment by an ACEI/ARB and a MRB may further decrease albuminuria in diabetic nephropathy. This effect may be due to the specific properties of the MRB treatment. Clinicians should regularly check potassium levels because of the increased risk of hyperkalemia. Available evidence should be confirmed by an adequately powered comparative trial of the standard treatment (ACEI or ARB) versus combined treatment by an ACEI/ARB and a MRB. Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial.

PubMed

Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D'Angelo, Valerio; Urso, Viviana

2015-01-01

The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization.

Combined Treatment with Interlukin-1 and Tumor Necrosis Factor-Alpha Antagonists Improve Type 2 Diabetes in Rats.

PubMed

DiK, Burak; Bahcivan, Emre; Eser Faki, Hatice; Uney, Kamil

2018-03-20

In the present study, combined treatment with etanercept and anakinra were tested in the streptozotocin-induced diabetic rats. Forty male Wistar albino rats were divided into 5 groups; healthy control (HC), diabetic control (DC), diabetic+anakinra (DAT), diabetic+etanercept (DET), and diabetic+etanercept+anakinra (DEAT). HC and DC groups received subcutaneous (sc.) injection with a saline solution, while DAT and DET groups received anakinra (10 mg/kg/day, sc.) or etanercept (10 mg/kg, twice a week, sc.), and DEAT rats received both anakinra and etanercept treatments for 21 days after diabetes has developed. Anakinra and etanercept treatments significantly increased insulin and homeostatic model assessment-β cell function levels and decreased glucose levels compared to the DC group as single (DAT and DET) and combined treatments (DEAT). The thiobarbituric acid reactive substances level was significantly decreased in DAT group. The combine use of etanercept and anakinra can improve insulin and blood glucose in type 2 diabetic rats. The combined treatment of anakinra and etanercept together was more effective than single treatment and might have a potential new treatment strategy and to reduce the mortality and morbidity resulting from diabetes.

Effectiveness of cognitive behavioral therapy integrated with systematic desensitization, cognitive behavioral therapy combined with eye movement desensitization and reprocessing therapy, and cognitive behavioral therapy combined with virtual reality exposure therapy methods in the treatment of flight anxiety: a randomized trial

PubMed Central

Triscari, Maria Teresa; Faraci, Palmira; Catalisano, Dario; D’Angelo, Valerio; Urso, Viviana

2015-01-01

The purpose of the research was to compare the effectiveness of the following treatment methods for fear of flying: cognitive behavioral therapy (CBT) integrated with systematic desensitization, CBT combined with eye movement desensitization and reprocessing therapy, and CBT combined with virtual reality exposure therapy. Overall, our findings have proven the efficacy of all interventions in reducing fear of flying in a pre- to post-treatment comparison. All groups showed a decrease in flight anxiety, suggesting the efficiency of all three treatments in reducing self-report measures of fear of flying. In particular, our results indicated significant improvements for the treated patients using all the treatment programs, as shown not only by test scores but also by participation in the post-treatment flight. Nevertheless, outcome measures maintained a significant effect at a 1-year follow-up. In conclusion, combining CBT with both the application of eye movement desensitization and reprocessing treatment and the virtual stimuli used to expose patients with aerophobia seemed as efficient as traditional cognitive behavioral treatments integrated with systematic desensitization. PMID:26504391

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

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder.

PubMed

Dold, M; Bartova, L; Mendlewicz, J; Souery, D; Serretti, A; Porcelli, S; Zohar, J; Montgomery, S; Kasper, S

2018-05-01

This multicenter, multinational, cross-sectional study aimed to investigate clinical characteristics and treatment outcomes associated with augmentation/combination treatment strategies in major depressive disorder (MDD). Sociodemographic, clinical, and treatment features of 1410 adult MDD patients were compared between MDD patients treated with monotherapy and augmentation/combination medication using descriptive statistics, analyses of covariance (ancova), and Spearman's correlation analyses. 60.64% of all participants received augmentation and/or combination strategies with a mean number of 2.18 ± 1.22 simultaneously prescribed psychiatric drugs. We found male gender, older age, Caucasian descent, higher weight, low educational status, absence of occupation, psychotic symptoms, melancholic and atypical features, suicide risk, in-patient treatment, longer duration of hospitalization, some psychiatric comorbidities (panic disorder, agoraphobia, obsessive-compulsive disorder, and bulimia nervosa), comorbid somatic comorbidity in general and concurrent hypertension, thyroid dysfunction, diabetes, and heart disease in particular, higher current and retrospective Montgomery and Åsberg Depression Rating Scale total scores, treatment resistance, and higher antidepressant dosing to be significantly associated with augmentation/combination treatment. These findings were corroborated when examining the number of concurrently administered psychiatric drugs in the statistical analyses. Our findings suggest a clear association between augmentation/combination strategies and treatment-resistant/difficult-to-treat MDD conditions characterized by severe symptomatology and high amount of psychiatric and somatic comorbidities. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Effect of Stretching Combined With Ultrashort Wave Diathermy on Joint Function and Its Possible Mechanism in a Rabbit Knee Contracture Model.

PubMed

Zhang, Quan Bing; Zhou, Yun; Zhong, Hua Zhang; Liu, Yi

2018-05-01

The aim of this study was to investigate the therapeutic effect of stretching combined with ultrashort wave on joint contracture and explore its possible mechanism. Thirty-two rabbits underwent unilateral immobilization of a knee joint at full extension to cause joint contracture. At 6 wks after immobilization, the rabbits were randomly divided into the following four groups: natural recovery group, stretching treatment group, ultrashort wave treatment group, and combined treatment group. For comparison, eight control group animals of corresponding age were also examined. The effect of stretching and ultrashort wave treatment on joint contracture was assessed by measuring the joint range of motion, evaluating the collagen deposition of joint capsule and assessing the mRNA and protein levels for transforming growth factor β1 in the joint capsule. The combined treatment group led to the best recovery of joint function. The combined treatment with stretching and ultrashort wave was more effective than stretching or ultrashort wave treatment alone against the synovial thickening of suprapatellar joint capsule, the collagen deposition of anterior joint capsule, and the elevated expression of transforming growth factor β1 in the joint capsule. Stretching combined with ultrashort wave treatment was effective in improving joint range of motion, reducing the biomechanical, histological, and molecular manifestations of joint capsule fibrosis in a rabbit model of extending joint contracture.

Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

PubMed

Alonso, L; Fontecha, J; Cuesta, P

2016-01-14

A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (P<0·05) for each of the individual treatment groups: BCD or L. acidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations.

Effect of a Combined Walking and Conversation Intervention on Functional Mobility of Nursing Home Residents With Alzheimer Disease

PubMed Central

Tappen, Ruth M.; Roach, Kathryn E.; Applegate, E. Brooks; Stowell, Paula

2007-01-01

Summary Assisted walking and walking combined with conversation were compared to a conversation-only intervention in nursing home residents with Alzheimer disease. Sixty-five subjects randomly assigned to treatment group were tested at baseline and end of treatment. Subjects mean Mini-Mental State Examination score was 10.83; mean age was 87. Treatment was given for 30 minutes three times a week for 16 weeks. Subjects in the assisted walking group declined 20.9% in functional mobility; the conversation group declined 18.8%. The combined walking and conversation treatment group declined only 2.5%. These differences in outcome were significant and appear to have been affected by differences in treatment fidelity. Subjects in the conversation treatment group completed 90% of intended treatment compared with 75% in the combined group and only 57% in the assisted walking group. Failure to treat was due to subject refusal and physical illness. The conversation component of the combined walking and conversation treatment intervention appears to have improved compliance with the intervention, thereby improving treatment outcome. Results indicate that assisted walking with conversation can contribute to maintenance of functional mobility in institutionalized populations with Alzheimer disease. Staff assigned to this task should be prepared to use effective communication strategies to gain acceptance of the intervention. PMID:11186596

[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.

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

Switch Rates During Acute Treatment for Bipolar II Depression With Lithium, Sertraline, or the Two Combined: A Randomized Double-Blind Comparison.

PubMed

Altshuler, Lori L; Sugar, Catherine A; McElroy, Susan L; Calimlim, Brian; Gitlin, Michael; Keck, Paul E; Aquino-Elias, Ana; Martens, Brian E; Fischer, E Grace; English, Teri L; Roach, Janine; Suppes, Trisha

2017-03-01

The authors compared medication-induced mood switch risk (primary outcome), as well as treatment response and side effects (secondary outcomes) with three acute-phase treatments for bipolar II depression. In a 16-week, double-blind, multisite comparison study, 142 participants with bipolar II depression were randomly assigned to receive lithium monotherapy (N=49), sertraline monotherapy (N=45), or combination treatment with lithium and sertraline (N=48). At each visit, mood was assessed using standardized rating scales. Rates of switch were compared, as were rates of treatment response and the presence and severity of treatment-emergent side effects. Twenty participants (14%) experienced a switch during the study period (hypomania, N=17; severe hypomania, N=3). Switch rates did not differ among the three treatment groups, even after accounting for dropout. No patient had a manic switch or was hospitalized for a switch. Most switches occurred within the first 5 weeks of treatment. The treatment response rate for the overall sample was 62.7% (N=89), without significant differences between groups after accounting for dropout. The lithium/sertraline combination group had a significantly higher overall dropout rate than the monotherapy groups but did not have an accelerated time to response. Lithium monotherapy, sertraline monotherapy, and lithium/sertraline combination therapy were associated with similar switch and treatment response rates in participants with bipolar II depression. The dropout rate was higher in the lithium/sertraline combination treatment group, without any treatment acceleration advantage.

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

PubMed Central

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

2014-01-01

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

Efficacy of antibiotic treatment of implant-associated Staphylococcus aureus infections with moxifloxacin, flucloxacillin, rifampin, and combination therapy: an animal study.

PubMed

Greimel, Felix; Scheuerer, Christine; Gessner, Andre; Simon, Michaela; Kalteis, Thomas; Grifka, Joachim; Benditz, Achim; Springorum, Hans-Robert; Schaumburger, Jens

2017-01-01

The efficacy of antibiotic monotherapy and combination therapy in the treatment of implant-associated infection by Staphylococcus aureus was evaluated in an animal study. The femoral medullary cavity of 66 male Wistar rats was contaminated with S. aureus (ATCC 29213) and a metal device was implanted, of which 61 could be evaluated. Six treatment groups were studied: flucloxacillin, flucloxacillin in combination with rifampin, moxifloxacin, moxifloxacin in combination with rifampin, rifampin, and a control group with aqua. The treatment was applied for 14 days. After euthanasia, the bacterial counts in the periprosthetic bone, the soft tissue, and the implant-associated biofilm were measured. Both antibiotic combination treatments (moxifloxacin plus rifampin and flucloxacillin plus rifampin) achieved a highly significant decrease in microbial counts in the bone and soft tissue and in the biofilm. Mono-antibiotic treatments with either moxifloxacin or flucloxacillin were unable to achieve a significant decrease in microbial counts in bone and soft tissue or the biofilm, whilst rifampin was able to reduce the counts significantly only in the biofilm. Antibiotic resistance was measured in 1/3 of the cases in the rifampin group, whereas no resistance was measured in all other groups. The results show that combinations of both moxifloxacin and flucloxacillin plus rifampin are adequate for the treatment of periprosthetic infections due to infections with S. aureus , whereas monotherapies are not effective or not applicable due to the rapid development of antibiotic resistance. Therefore, moxifloxacin is an effective alternative in combination with rifampin for the treatment of implant-associated infections.

[Establishment of nude mouse model with ovarian carcinomaand the effect of Paris Phyllin VII combined with silica nano complex on the inhibition and the antioxidant ability of ovarian carcinoma in nude mice].

PubMed

Chen, Jun; Wang, Bihang; Zhang, Jialing; Yang, Ruiqi; Fan, Limei

2015-08-04

To establish the research model of ovarian carcinoma in nude mice, and to explore the effect of Paris Phyllin VII combined with silica nano complex on the inhibition and the antioxidant ability of ovarian carcinoma in nude mice. Nude mice models with ovarian carcinoma were established by axillary subcutaneous inoculation of human SKOV3/DDP resistant ovarian cancer cell 200 µl and were used in the experiment. Treating the nude mice with Paris Phyllin VII combined with silica nano complex by gavage for 15 days to observe the weight change of the nude mice, tumor inhibition effect and changes of serum antioxidant capacity. Compared with the negative control group, tumor inhibition rate increased significantly in Paris Phyllin VII combined with silica nano complex treatment group, and was higher than that in both Paris Phyllin VII treatment only and silica nano composites treatment only group. The serum superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) level of Paris Phyllin VII combined with silica nano complex treatment group was significantly higher than that of control group, Paris Phyllin VII treatment only and silica nano composites treatment only group. The serum malonaldehyde (MDA) level of Paris Phyllin VII combined with silica nano complex treatment group was significantly lower than that of the negative control group. Paris Phyllin VII combined with silica nano complex treatment can inhibit the ovarian carcinoma in nude mice, which may mediate by the enhancement of antioxidant capability in nude mice with ovarian cancer.

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.

Outcomes of combined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial.

PubMed

Margolis, Karen L; O'Connor, Patrick J; Morgan, Timothy M; Buse, John B; Cohen, Robert M; Cushman, William C; Cutler, Jeffrey A; Evans, Gregory W; Gerstein, Hertzel C; Grimm, Richard H; Lipkin, Edward W; Narayan, K M Venkat; Riddle, Matthew C; Sood, Ajay; Goff, David C

2014-06-01

To compare effects of combinations of standard and intensive treatment of glycemia and either blood pressure (BP) or lipids in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. ACCORD enrolled 10,251 type 2 diabetes patients aged 40-79 years at high risk for cardiovascular disease (CVD) events. Participants were randomly assigned to hemoglobin A1c goals of <6.0% (<42 mmol/mol; intensive glycemia) or 7.0-7.9% (53-63 mmol/mol; standard glycemia) and then randomized a second time to either 1) systolic BP goals of <120 mmHg (intensive BP) or <140 mmHg (standard BP) or 2) simvastatin plus fenofibrate (intensive lipid) or simvastatin plus placebo (standard lipid). Proportional hazards models were used to assess combinations of treatment assignments on the composite primary (deaths due to CVD, nonfatal myocardial infarction [MI], and nonfatal stroke) and secondary outcomes. In the BP trial, risk of the primary outcome was lower in the groups intensively treated for glycemia (hazard ratio [HR] 0.67; 95% CI 0.50-0.91), BP (HR 0.74; 95% CI 0.55-1.00), or both (HR 0.71; 95% CI 0.52-0.96) compared with combined standard BP and glycemia treatment. For secondary outcomes, MI was significantly reduced by intensive glycemia treatment and stroke by intensive BP treatment; most other HRs were neutral or favored intensive treatment groups. In the lipid trial, the general pattern of results showed no evidence of benefit of intensive regimens (whether single or combined) compared with combined standard lipid and glycemia treatment. The mortality HR was 1.33 (95% CI 1.02-1.74) in the standard lipid/intensive glycemia group compared with the standard lipid/standard glycemia group. In the ACCORD BP trial, compared with combined standard treatment, intensive BP or intensive glycemia treatment alone improved major CVD outcomes, without additional benefit from combining the two. In the ACCORD lipid trial, neither intensive lipid nor glycemia treatment produced an overall benefit, but intensive glycemia treatment increased mortality. © 2014 by the American Diabetes Association.

A Prospective Open-Label Study of Combined Treatment for Idiopathic Parkinson's Disease Using Acupuncture and Bee Venom Acupuncture as an Adjunctive Treatment.

PubMed

Doo, Kyeong-Hee; Lee, Ji-Hyun; Cho, Seung-Yeon; Jung, Woo-Sang; Moon, Sang-Kwan; Park, Jung-Mi; Ko, Chang-Nam; Kim, Ho; Park, Hi-Joon; Park, Seong-Uk

2015-10-01

The purpose of this study was to examine the effectiveness and safety of combined treatment using acupuncture and bee venom acupuncture (BVA) as an adjunctive treatment for idiopathic Parkinson's disease (PD). Eleven patients (7 men and 4 women) with idiopathic PD who had been receiving a stable dose of anti-parkinsonian medication for at least 4 weeks. Participants received conventional treatment for 12 weeks. Subsequently, they received additional treatment with acupuncture and BVA twice weekly for 12 weeks while still maintaining conventional treatment. All participants were assessed at baseline, 12 weeks, and 24 weeks by using the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Quality of Life Questionnaire (PDQL), the speed and number of steps required to walk 20 m, and the Beck Depression Inventory (BDI). Maximum excursion and directional control, measured by computerized dynamic posturography (Balance Master(®) System, NeuroCom, San Carlos, CA), were used to assess postural stability. Patients who underwent 12 weeks of twice-weekly combined treatment with acupuncture and BVA showed significant improvements in gait speed, PDQL score, activities of daily living (UPDRS part II), motor symptoms (UPDRS part III), and combined UPDRS part II+III scores compared with assessments after conventional treatment. Combined treatment with acupuncture and BVA showed promising results as a safe adjunctive therapy for PD.

Correlations of plasma renin activity and aldosterone concentration with ambulatory blood pressure responses to nebivolol and valsartan, alone and in combination, in hypertension.

PubMed

Giles, Thomas D; Bakris, George; Oparil, Suzanne; Weber, Michael A; Li, Huiling; Mallick, Madhuja; Bharucha, David B; Chen, ChunLin; Ferguson, William G

2015-11-01

After demonstration of the antihypertensive efficacy of the combination of the beta-blocker nebivolol and the angiotensin receptor blocker valsartan in an 8-week, randomized, placebo-controlled trial (N = 4161), we now report the effects of this treatment on the renin-angiotensin-aldosterone system in a substudy (n = 805). Plasma renin activity increased with valsartan (54%-73%) and decreased with nebivolol (51%-65%) and the combination treatment (17%-39%). Plasma aldosterone decreased with individual treatments (valsartan, 11%-22%; nebivolol, 20%-26%), with the largest reduction (35%) observed with maximum combination dose (20 mg nebivolol/320 mg valsartan). Baseline ln(plasma renin activity) correlated with the 8-week reductions in 24-hour systolic and diastolic BP following treatments with the combination (all doses combined, P = .003 and P < .001) and nebivolol (both, P < .001), but not with valsartan. Baseline ln(aldosterone) correlated with 24-hour systolic and diastolic BP reductions following combination treatment only (P < .001 and P = .005). The implications of the renin-angiotensin-aldosterone system effects of this beta blocker-angiotensin receptor blocker combination should be explored further. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Oral combination therapy: repaglinide plus metformin for treatment of type 2 diabetes.

PubMed

Raskin, P

2008-12-01

Type 2 diabetes is characterized by decreases in insulin secretion and insulin sensitivity. Several classes of oral antidiabetic medications are currently approved for the treatment of type 2 diabetes. A stepwise treatment approach from monotherapy to combination therapy is traditionally used; however, the frequency of treatment failure with monotherapy has resulted in a move towards earlier treatment with combination therapies that target the two principal defects in glycaemic control. One such combination regimen is repaglinide (a prandial glucose regulator that increases insulin release) plus metformin (an insulin sensitizer that inhibits hepatic glucose output, increases peripheral glucose uptake and utilization and minimizes weight gain). Findings from several clinical trials have shown that combination therapy with repaglinide plus metformin is well tolerated and results in greater reductions of haemoglobin A(1c) and fasting plasma glucose values compared with either monotherapy. Repaglinide may also provide a more suitable alternative to combination therapy with sulphonylureas and metformin because of its reduced propensity for hypoglycaemia. The combination regimen of repaglinide plus metformin should therefore be considered as a valuable option in the management of patients with type 2 diabetes when monotherapy is no longer adequate.

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.

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.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines

PubMed Central

Yi, Jin-Ling; Shi, Song; Shen, Yan-Li; Wang, Ling; Chen, Hai-Yan; Zhu, Jun; Ding, Yan

2015-01-01

Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer. PMID:25972998

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

PubMed

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

2018-02-15

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

Surgical treatment of gynecomastia: liposuction combined with subcutaneous mastectomy.

PubMed

Boljanovic, S; Axelsson, C K; Elberg, J J

2003-01-01

The purpose of the present work has been to evaluate surgical treatment of gynecomastia performed by liposuction combined with subcutaneous mastectomy. It was designed as a prospective consecutive registration of 21 patients (28 breasts) operated in a four month period. Treatment was done in local anaesthesia in the out-patient clinic. Treatment was in one patient complicated with a haematoma. In 86% of cases the patients were satisfied with the postoperative result. Liposuction combined with surgical excision of the gland performed as an out-patient treatment in local anaesthesia is followed by few complications and good cosmetic results.

Sorafenib and triptolide as combination therapy for hepatocellular carcinoma.

PubMed

Alsaied, Osama A; Sangwan, Veena; Banerjee, Sulagna; Krosch, Tara C; Chugh, Rohit; Saluja, Ashok; Vickers, Selwyn M; Jensen, Eric H

2014-08-01

Sorafenib is the only drug approved by the Food and Drug Administration for metastatic hepatocellular carcinoma (HCC). Triptolide, a diterpene triepoxide, exhibits antineoplastic properties in multiple tumor cell types. In this study, we examined the effects of these agents and their combination on HCC in vitro and in vivo models. HuH-7 and PLC/PRF/5 cells were treated with triptolide (50 nM), sorafenib (1.25 or 2.5 μM), or a combination of both. Cell viability assay (CCK-8), caspase 3&7 activation, and nuclear factor κB assays were performed. For in vivo studies, 40 mice were implanted with subcutaneous HuH7 tumors and divided into four treatment groups (n = 10); saline control, sorafenib 10 mg/kg PO daily (S), Minnelide (a prodrug of triptolide) 0.21 mg/kg intraperitoneally7 daily (M), and combination of both (C). Tumor volumes were assessed weekly. The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis and decreasing viability, whereas triptolide alone was sufficient to decrease nuclear factor κB activity. After 2 weeks of treatment, tumor growth inhibition rates were S = 59%, M = 84%, and C = 93%, whereas tumor volumes in control animals increased by 9-fold. When crossed over to combination treatment, control mice tumor growth volumes plateaued over the following 4 weeks. The combination of sorafenib and triptolide is superior to single drug treatment in increasing cell death and apoptosis in vitro. Combining sorafenib with Minnelide inhibited tumor growth with greater efficacy than single-agent treatments. Importantly, in vivo combination treatment allowed for using a lesser dose of sorafenib (10 mg/kg), which is less than 10% of currently prescribed dose for HCC patients. Therefore, combination treatment could have translational potential in the management of HCC. Copyright © 2014 Mosby, Inc. All rights reserved.

Evidence for Adverse Phonatory Change Following an Inhaled Combination Treatment

ERIC Educational Resources Information Center

Erickson, Elizabeth; Sivasankar, Mahalakshmi

2010-01-01

Purpose: Voice problems are reported as a frequent side effect of inhaled combination (IC) treatments. The purpose of this experimental study was to investigate whether IC treatments are detrimental to phonation. We hypothesized that IC treatment would significantly increase phonation threshold pressure (PTP) and perceived phonatory effort (PPE),…

Fractionation of rapeseed straw by hydrothermal/dilute acid pretreatment combined with alkali post-treatment for improving its enzymatic hydrolysis.

PubMed

Chen, Bo-Yang; Zhao, Bao-Cheng; Li, Ming-Fei; Liu, Qiu-Yun; Sun, Run-Cang

2017-02-01

The aim of the research was to evaluate the effect of combined treatments on fermentable sugar production from rapeseed straw. An optimum condition was found to be the combination of hydrothermal pretreatment at 180°C for 45min and post-treatment by 2% NaOH at 100°C for 2h, which was based on the quantity of monosaccharides released during enzymatic hydrolysis. As compared with the raw material without treatment, the combination of hydrothermal pretreatment and alkali post-treatment resulted in a significant increase of the saccharification rate by 5.9times. This process potentially turned rapeseed straw into value added products in accordance with the biorefinery concept. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Case Report: Successful Use of the Combination of Electroconvulsive Therapy and Clozapine in Treating Treatment-Resistant Schizophrenia and Catatonia in an Adult with Intellectual Disability.

PubMed

Desarkar, Pushpal; Blumberger, Daniel; Daskalakis, Zafiris Jeff

2018-04-25

There is paucity of empirical data regarding the use of either clozapine or electroconvulsive therapy (ECT) in the acute phase and maintenance treatment of schizophrenia in adults with intellectual disability. Herein we report the successful acute and long-term remission of psychotic symptoms and catatonia with the combination of clozapine and ECT in a 26-year-old female with moderate ID and treatment-resistant schizophrenia. To our knowledge, this is the first case example of the successful use of the combination of bilateral, standard-pulse ECT and clozapine in both acute and long-term treatment of treatment-resistant schizophrenia and catatonia in an adult with ID. Our report adds further support to the emerging evidence regarding the efficacy and safety of this combination in treatment-resistant schizophrenia.

Parent-Reported Homework Problems in the MTA Study: Evidence for Sustained Improvement with Behavioral Treatment

PubMed Central

Langberg, Joshua M.; Arnold, L. Eugene; Flowers, Amanda M.; Epstein, Jeffery N.; Altaye, Mekibib; Hinshaw, Stephen P.; Swanson, James M.; Kotkin, Ronald; Simpson, Stephen; Molina, Brooke S.G.; Jensen, Peter S.; Abikoff, Howard; Pelham, William E.; Vitiello, Benedetto; Wells, Karen C.; Hechtman, Lily

2011-01-01

Parent-report of child homework problems was examined as a treatment outcome variable in the MTA - Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder (ADHD). Five hundred seventy-nine children ages 7.0–9.9 were randomly assigned to either medication management, behavioral treatment, combination treatment, or routine community care. Results showed that only participants who received behavioral treatment (behavioral and combined treatment) demonstrated sustained improvements in homework problems in comparison to routine community care. The magnitude of the sustained effect at the 24-month assessment was small to moderate for combined and behavioral treatment over routine community care (d = .37; .40, respectively). Parent ratings of initial ADHD symptom severity was the only variable found to moderate these effects. PMID:20390813

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

PubMed

Wolbers, Marcel; Heemskerk, Dorothee; Chau, Tran Thi Hong; Yen, Nguyen Thi Bich; Caws, Maxine; Farrar, Jeremy; Day, Jeremy

2011-02-02

In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design. We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Current Controlled Trials ISRCTN61649292.

A special terpene combination (Rowatinex®) improves stone clearance after extracorporeal shockwave lithotripsy in urolithiasis patients: results of a placebo-controlled randomised controlled trial.

PubMed

Romics, Imre; Siller, György; Kohnen, Ralf; Mavrogenis, Stelios; Varga, József; Holman, Endre

2011-01-01

To investigate the safety and efficacy of a special terpene combination in the treatment of patients with urolithiasis after extracorporeal shockwave lithotripsy (ESWL). 222 patients with clinically stable kidney or ureter stones of 0.3-2.0 cm undergoing complication-free ESWL were randomised to receive a special terpene combination (Rowatinex®; 3 × 2 capsules/day) or placebo. The study consisted of a 12-week active treatment phase and a 2-week follow-up phase. All patients had a physical examination, and diagnosis of kidney stones was made by X-ray, intravenous pyelogram or ultrasound at weeks 1, 4, 8 and 12 as well as after 2 weeks of follow-up. Stone-free status was defined as obviously successful expulsion of calculi/fragments, being without any stone. In all, when compared to placebo, significantly more patients receiving the terpene combination treatment in the intent-to-treat (ITT) group [72 (67.9%) vs. 49 (50.0%); p = 0.0009] and the per-protocol (PP) group [69 (78.4%) vs. 48 (52.2%); p = 0.0004] were stone-free at the end of the study. Treatment with the terpene combination was also more effective when analysed with respect to the size of the treated stone. In addition, treatment with the terpene combination significantly reduced the median time to stone-free status from 85.0 to 56.0 days (p = 0.0061) and from 85.0 to 49.5 days (p = 0.0028) in the ITT and PP populations, respectively. Nine mild-to-moderate adverse events (AE; terpene combination group: 7 AE in 4 patients; placebo group: 2 AE in 2 patients) were assessed as drug-related. Treatment with the terpene combination is well tolerated and safe. The terpene combination was found to be an efficacious treatment in eliminating calculi fragments generated by ESWL as compared to placebo. The pharmacodynamic properties of the terpene combination (antilithogenic, antibacterial, antiinflammatory, spasmolytic and analgesic effects), which have been also confirmed in preclinical studies, represent a valuable alternative to the different drugs used in the treatment of urolithiasis. Copyright © 2010 S. Karger AG, Basel.

Effects of sonication and ultraviolet-C treatment as a hurdle concept on quality attributes of Chokanan mango (Mangifera indica L.) juice.

PubMed

Santhirasegaram, Vicknesha; Razali, Zuliana; Somasundram, Chandran

2015-04-01

The growing demand for fresh-like food products has encouraged the development of hurdle technology of non-thermal processing. In this study, freshly squeezed Chokanan mango juice was treated by paired combinations of sonication (for 15 and 30 min at 25 ℃, 40 kHz frequency) and UV-C treatment (for 15 and 30 min at 25 ℃). Selected physicochemical properties, antioxidant activities, microbial inactivation and other quality parameters of combined treated juice were compared to conventional thermal treatment (at 90 ℃ for 60 s). After thermal and combined treatment, no significant changes occurred in physicochemical properties. A significant increase in extractability of carotenoids (15%), polyphenols (37%), flavonoids (35%) and enhancement in antioxidant capacity was observed after combined treatment. Thermal and combined treatment exhibited significant reduction in microbial load. Results obtained support the use of sonication and UV-C in a hurdle technology to improve the quality of Chokanan mango juice along with safety standards. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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.

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

Drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection.

PubMed

Xu, Chuan; Huang, Xin-En; Wang, Shu-Xiang; Lv, Peng-Hua; Sun, Ling; Wang, Fu-An; Wang, Li-Fu

2014-01-01

To compare drainage alone or combined with anti-tumor therapy for treatment of obstructive jaundice caused by recurrence and metastasis after primary tumor resection. We collect 42 patients with obstructive jaundice caused by recurrence and metastasis after tumor resection from January 2008 - August 2012, for which percutaneous transhepatic catheter drainage (pTCD)/ percutaneous transhepatic biliary stenting (pTBS) were performed. In 25 patients drainage was combined with anti-tumor treatment, antineoplastic therapy including intra/postprodure local treatment and postoperative systemic chemotherapy, the other 17 undergoing drainage only. We assessed the two kinds of treatment with regard to patient prognosis. Both treatments demonstrated good effects in reducing bilirubin levels in the short term and promoting liver function. The time to reobstruction was 125 days in the combined group and 89 days in the drainage only group; the mean survival times were 185 and 128 days, the differences being significant. Interventional drainage in the treatment of the obstructive jaundice caused by recurrence and metastasis after tumor resection can decrease bilirubin level quickly in a short term and promote the liver function recovery. Combined treatment prolongs the survival time and period before reobstruction as compared to drainage only.

Catalytic Effect of Activated Carbon and Activated Carbon Fiber in Non-Equilibrium Plasma-Based Water Treatment

NASA Astrophysics Data System (ADS)

Zhang, Yanzong; Zheng, Jingtang; Qu, Xianfeng; Yu, Weizhao; Chen, Honggang

2008-06-01

Catalysis and regeneration efficiency of granular activated carbon (GAC) and activated carbon fiber (ACF) were investigated in a non-equilibrium plasma water treatment reactor with a combination of pulsed streamer discharge and GAC or ACF. The experimental results show that the degradation efficiency of methyl orange (MO) by the combined treatment can increase 22% (for GAC) and 24% (for ACF) respectively compared to pulsed discharge treatment alone, indicating that the combined treatment has a synergetic effect. The MO degradation efficiency by the combined treatment with pulsed discharge and saturated GAC or ACF can increase 12% and 17% respectively compared to pulsed discharge treatment alone. Both GAC and ACF show catalysis and the catalysis of ACF is prominent. Meanwhile, the regeneration of GAC and ACF are realized in this process. When H2O2 is introduced into the system, the utilization efficiency of ozone and ultraviolet light is improved and the regeneration efficiency of GAC and ACF is also increased.

Effect of combined treatment with supercritical CO2 and rosemary on microbiological and physicochemical properties of ground pork stored at 4°C.

PubMed

Huang, Shirong; Liu, Bin; Ge, Du; Dai, Jiehui

2017-03-01

The effect of combined treatment with supercritical CO 2 (2000psi, 35°C for 2h) and rosemary powder (2.5% and 5.0% (w/w)) on microbiological and physicochemical properties of ground pork stored at 4°C was investigated. The changes in total viable count, pH, total volatile base nitrogen (TVB-N), lipid oxidation and instrumental color (CIE L ⁎ , a ⁎ , b ⁎ ) were analyzed during a week period of refrigerated storage. It was found that microbial populations were reduced by supercritical CO 2 treatment, with the more pronounced effect being achieved by combined treatment with supercritical CO 2 and 5.0g rosemary powder/100g meat. Supercritical CO 2 treatment for 2h could accelerate lipid oxidation of ground pork during refrigerated storage, whereas combination with rosemary can significantly slow down the increase of oxidation rate. Combined treatment of supercritical CO 2 and rosemary significantly increased L ⁎ and b ⁎ values of the ground pork, while the a ⁎ , pH and TVB-N value were not affected as compared to the treatment with supercritical CO 2 alone. The results of this study indicate that combined treatment of supercritical CO 2 and rosemary may be useful in the meat industry to enhance the storage stability of ground pork treated with long time exposure of supercritical CO 2 during refrigerated storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Efficacy and safety of combined treatment of miniscalpel acupuncture and non-steroidal anti-inflammatory drugs: an assessor-blinded randomized controlled pilot study.

PubMed

Jun, Seungah; Lee, Jung Hee; Gong, Han Mi; Chung, Yeon-Joong; Kim, Ju-Ran; Park, Chung A; Choi, Seong Hun; Lee, Geon-Mok; Lee, Hyun-Jong; Kim, Jae Soo

2018-01-12

Chronic neck pain is a common musculoskeletal disease during the lifespan of an individual. With an increase in dependence on computer technology, the prevalence of chronic neck pain is expected to rise and this can lead to socioeconomic problems. We have designed the current pilot study to evaluate the efficacy and safety of miniscalpel acupuncture treatment combined with non-steroidal anti-inflammatory drugs (NSAIDs) in patients with chronic neck pain. This seven-week clinical trial has been designed as an assessor-blinded, randomized controlled trial with three parallel arms. Thirty-six patients will be recruited and randomly allocated to three treatment groups: miniscalpel acupuncture treatment; NSAIDs; and miniscalpel acupuncture treatment combined with NSAIDs. Patients in the miniscalpel acupuncture and combined treatment groups will receive three sessions of miniscalpel acupuncture over a three-week period. Patients in the NSAIDs and combined treatment groups will receive zaltoprofen (one oral tablet, three times a day for three weeks). Primary and secondary outcomes will be measured at weeks 0 (baseline), 1, 2, 3 (primary end point), and 7 (four weeks after treatment completion) using the visual analogue scale and the Neck Disability Index, EuroQol 5-dimension questionnaire, and Patients' Global Impression of Change scale, respectively. Adverse events will also be recorded. This pilot study will provide a basic foundation for a future large-scale trial as well as information about the feasibility of miniscalpel acupuncture treatment combined with NSAIDs for chronic neck pain. Korean Clinical Research Information Service registry, KCT0002258 . Registered on 9 March 2017.

Combined prolonged exposure therapy and paroxetine for PTSD related to the World Trade Center attack: a randomized controlled trial.

PubMed

Schneier, Franklin R; Neria, Yuval; Pavlicova, Martina; Hembree, Elizabeth; Suh, Eun Jung; Amsel, Lawrence; Marshall, Randall D

2012-01-01

Selective serotonin reuptake inhibitors (SSRIs) are often recommended in combination with established cognitive-behavioral therapies (CBTs) for posttraumatic stress disorder (PTSD), but combined initial treatment of PTSD has not been studied under controlled conditions. There are also few studies of either SSRIs or CBT in treating PTSD related to terrorism. The authors compared prolonged exposure therapy (a CBT) plus paroxetine (an SSRI) with prolonged exposure plus placebo in the treatment of terrorism-related PTSD. Adult survivors of the World Trade Center attack of September 11, 2001, with PTSD were randomly assigned to 10 weeks of treatment with prolonged exposure (10 sessions) plus paroxetine (N=19) or prolonged exposure plus placebo (N=18). After week 10, patients discontinued prolonged exposure and were offered 12 additional weeks of continued randomized treatment. Patients treated with prolonged exposure plus paroxetine experienced significantly greater improvement in PTSD symptoms (incidence rate ratio=0.50, 95% CI=0.30-0.85) and remission status (odds ratio=12.6, 95% CI=1.23-129) during 10 weeks of combined treatment than patients treated with prolonged exposure plus placebo. Response rate and quality of life were also significantly more improved with combined treatment. The subset of patients who continued randomized treatment for 12 additional weeks showed no group differences. Initial treatment with paroxetine plus prolonged exposure was more efficacious than prolonged exposure plus placebo for PTSD related to the World Trade Center attack. Combined treatment medication and prolonged exposure therapy deserves further study in larger samples with diverse forms of PTSD and over longer follow-up periods.

Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A—Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations

PubMed Central

Liew, Steven; Signorini, Massimo; Vieira Braz, André; Fagien, Steven; Swift, Arthur; De Boulle, Koenraad L.; Raspaldo, Hervé; Trindade de Almeida, Ada R.; Monheit, Gary

2016-01-01

Background: Combination of fillers and botulinum toxin for aesthetic applications is increasingly popular. Patient demographics continue to diversify, and include an expanding population receiving maintenance treatments over decades. Methods: A multinational panel of plastic surgeons and dermatologists convened the Global Aesthetics Consensus Group to develop updated guidelines with a worldwide perspective for hyaluronic acid fillers and botulinum toxin. This publication considers strategies for combined treatments, and how patient diversity influences treatment planning and outcomes. Results: Global Aesthetics Consensus Group recommendations reflect increased use of combined treatments in the lower and upper face, and some midface regions. A fully patient-tailored approach considers physiologic and chronologic age, ethnically associated facial morphotypes, and aesthetic ideals based on sex and culture. Lower toxin dosing, to modulate rather than paralyze muscles, is indicated where volume deficits influence muscular activity. Combination of toxin with fillers is appropriate for several indications addressed previously with toxin alone. New scientific data regarding hyaluronic acid fillers foster an evidence-based approach to selection of products and injection techniques. Focus on aesthetic units, rather than isolated rhytides, optimizes results from toxin and fillers. It also informs longitudinal treatment planning, and analysis of toxin nonresponders. Conclusions: The emerging objective of injectable treatment is facial harmonization rather than rejuvenation. Combined treatment is now a standard of care. Its use will increase further as we refine the concept that aspects of aging are intimately related, and that successful treatment entails identifying and addressing the primary causes of each. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V. PMID:27119917

Therapeutic Efficacy of Adenoviral-Mediated p53 Gene Transfer Is Synergistically Enhanced by Combined Use of Antisense Oligodeoxynucleotide Targeting Clusterin Gene in a Human Bladder Cancer Model1

PubMed Central

Miyake, Hideaki; Yamanaka, Kazuki; Muramaki, Mototsugu; Hara, Isao; Gleave, Martin E

2005-01-01

Abstract To establish a more effective therapeutic strategy against advanced bladder cancer, we investigated the effects of combined treatment with antisense (AS) oligodeoxynucleotide (ODN) targeting the antiapoptotic gene clusterin and adenoviral-mediated p53 gene transfer (Ad5CMV-p53) using the human bladder cancer KoTCC-1 model. Clusterin expression in KoTCC-1 cells was highly upregulated by Ad5CMV-p53 treatment; however, AS clusterin ODN treatment further suppressed clusterin expression in KoTCC-1 cells after Ad5CMV-p53 treatment. AS clusterin ODN treatment synergistically enhanced the cytotoxic effect of Ad5CMV-p53, and DNA fragmentation characteristic of apoptosis was observed only after combined treatment with AS clusterin ODN and Ad5CMV-p53, but not after treatment with either agent alone. Administration of AS clusterin ODN and Ad5CMV-p53 into nude mice resulted in a significant inhibition of KoTCC-1 tumor growth as well as lymph node metastases compared to administration of either agent alone. Furthermore, combined treatment with AS clusterin ODN, Ad5CMV-p53, and cisplatin completely eradicated KoTCC-1 tumors and lymph node metastases in 60% and 100% of mice, respectively. These findings suggest that combined treatment with AS clusterin ODN and Ad5CMV-p53 could be a novel strategy to inhibit bladder cancer progression, and that further additional use of a chemotherapeutic agent may substantially enhance the efficacy of this combined regimen. PMID:15802022

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

ERIC Educational Resources Information Center

Wells, Karen C.; Albano, Anne Marie

2005-01-01

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

Lethal trap trees and semiochemical repellents as area host protection strategies for spruce beetle (Coleoptera: Curculionidae, Scolytinae) in Utah

Treesearch

Matt Hansen; A. Steven Munson; Darren C. Blackford; David Wakarchuk; Scott Baggett

2016-01-01

We tested lethal trap trees and repellent semiochemicals as area treatments to protect host trees from spruce beetle (Dendroctonus rufipennis Kirby) attacks. Lethal trap tree treatments ("spray treatment") combined a spruce beetle bait with carbaryl treatment of the baited spruce. Repellent treatments ("spray-repellent”) combined a baited lethal...

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.

Combination treatment with docetaxel and histone deacetylase inhibitors downregulates androgen receptor signaling in castration-resistant prostate cancer.

PubMed

Park, Sang Eun; Kim, Ha-Gyeong; Kim, Dong Eun; Jung, Yoo Jung; Kim, Yunlim; Jeong, Seong-Yun; Choi, Eun Kyung; Hwang, Jung Jin; Kim, Choung-Soo

2018-04-01

Backgrounds Since most patients with castration-resistant prostate cancer (CRPC) develop resistance to its standard therapy docetaxel, many studies have attempted to identify novel combination treatment to meet the large clinical unmet need. In this study, we examined whether histone deacetylase inhibitors (HDACIs) enhanced the effect of docetaxel on AR signaling in CRPC cells harboring AR and its splice variants. Methods HDACIs (vorinostat and CG200745) were tested for their ability to enhance the effects of docetaxel on cell viability and inhibition of AR signaling in CRPC 22Rv1 and VCaP cells by using CellTiter-Glo™ Luminescent cell viability assay, synergy index analysis and Western blotting. The nuclear localization of AR was examined via immunocytochemical staining in 22Rv1 cells and primary tumor cells from a patient with CRPC. Results Combination treatment with HDACIs (vorinostat or CG200745) and docetaxel synergistically inhibited the growth of 22Rv1 and VCaP cells. Consistently, the combination treatment decreased the levels of full-length AR (AR-FL), AR splice variants (AR-Vs), prostate-specific antigen (PSA), and anti-apoptotic Bcl-2 proteins more efficiently compared with docetaxel or vorinostat alone. Moreover, the combination treatment accelerated the acetylation and bundling of tubulin, which significantly inhibited the nuclear accumulation of AR in 22Rv1 cells. The cytoplasmic colocalization of AR-FL and AR-V7 with microtubule bundles increased after combination treatment in primary tumor cells from a patient with CRPC. Conclusions The results suggested that docetaxel, in combination with HDACIs, suppressed the expression and nuclear translocation of AR-FL and AR-Vs and showed synergistic anti-proliferative effect in CRPC cells. This combination therapy may be useful for the treatment of patients with CRPC.

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

[Evaluating an effectiveness of surgical treatment of gastroesophageal reflux disease combined with hiatal hernia].

PubMed

Mozharovskiy, V V; Tsyganov, A A; Mozharovskiy, K V; Tarasov, A A

To assess an effectiveness of surgical treatment of gastroesophageal reflux disease (GERD) combined with hiatal hernia (HH). The trial included 96 patients with GERD and HH who were divided into 2 groups. The principal difference between groups was the use of surgery in the main group and therapeutic treatment in the comparison group. The effectiveness of surgical treatment is superior to therapeutic treatment of GERD by more than 2.5 times. HH combined with GERD is an indication for surgical treatment. Fundoplication cuff should not lead to angular and rotational esophageal deformation. Nissen procedure in Donahue modification (Short Floppy Nissen) simulates optimally the geometry of esophago-gastric junction and His angle.

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.

Synergic carcinostatic effects of ascorbic acid and hyperthermia on Ehrlich ascites tumor cell.

PubMed

Saitoh, Y; Yoshimoto, T; Kato, S; Miwa, N

2015-06-01

In this study, we evaluated the carcinostatic effects of combined ascorbic acid (AsA) and a capacitive-resistive electric transfer (CRet) hyperthermic apparatus-induced hyperthermic treatment on Ehrlich ascites tumor (EAT) cells. EAT cells were exposed to various AsA (0-10 mM) concentrations for 1 h; they subsequently underwent CRet treatment for 15 min at 42 °C. Cell viability was assessed by the WST-8 assay 24 h after the combined treatment. Reactive oxygen species involvement was evaluated using catalase and tempol; caspase-3/7 activation was determined by their fluorescent substrates; cell proliferation were estimated by time-lapse observation. The effect on the cell cycle was analyzed by flow cytometry. Combined AsA and CRet treatment synergistically suppressed cell viability compared with either treatment alone, and these synergistically carcinostatic effects were evident even at noncytotoxic concentrations of AsA alone (≤ 2 mM). The carcinostatic effects of combined AsA and CRet treatment were attenuated in a dose-dependent manner by catalase addition, but not by the superoxide anion radical scavenger tempol. Time-lapse observation revealed that combined AsA and CRet treatment activated caspase-3/7 at 10-24 h after treatment, accompanied by significant cell growth suppression. Cell cycle analysis revealed that the rate of sub-G1-phase (apoptotic) cells was drastically increased at 12 h and 24 h, and that the G2/M-phase cells gradually increased at 6-24 h after treatment. These results indicate that combined AsA and CRet treatment synergistically inhibits EAT cell growth through G2/M arrest and apoptosis induction via H2O2 generation at lower AsA concentrations; this carcinostatic effect cannot be exerted by AsA alone.

Effects of nitrate and atrazine on larval development and sexual differentiation in the northern leopard frog Rana pipiens.

PubMed

Orton, Frances; Carr, James A; Handy, Richard D

2006-01-01

Pollution from agrochemicals may be contributing to the global decline in amphibian populations. Environmentally relevant concentrations of nitrate and/or atrazine on anuran development and gonadal differentiation were tested. Four replicates of 20 tadpoles per tank (80/treatment) were exposed from Taylor-Kollros stage 2 to 3 to stage 23 to 34 to either 10 mg/L nitrate, 10 microg/L atrazine, a combined exposure of 10 mg/L nitrate plus 10 microg/L atrazine, or untreated controls. No treatment-dependent effects on weight, snout-vent or hind limb length, or time to forelimb emergence were observed. The proportions of females increased in all treatments compared to the controls, especially in the combined treatment (chi2 = 17.90, df = 6, p = 0.0065, combined = 66.4% female, control = 41% female). The frequency of intersex was low in all treatments. No treatment-related effects on the total number of spermatogenic cells were observed, but the ratio of cell types differed in that testes from animals in the treated groups exhibited more spermatogonia, fewer spermatocytes, and more spermatids than the control (significantly different, Kruskal-Wallis, p < 0.05). Ovaries from animals treated with nitrate or atrazine exhibited larger immature (previtellogenic) and mature (vitellogenic) follicles, but ovaries from the combined treatment had larger immature follicles only. Testicular oocytes were observed in the nitrate-only and atrazine-only treatments, and the control treatment, but not the combined treatment. Overall, this study has demonstrated changes in sex ratios that are more marked in response to combined nitrate/atrazine exposure than with these chemicals alone. Histological evidence suggests that premature maturation of gonad may occur as a result of nitrate and/or atrazine exposure during larval development.

[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.

Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris.

PubMed

Pazoki-Toroudi, Hamidreza; Nilforoushzadeh, Mohamad Ali; Ajami, Marjan; Jaffary, Fariba; Aboutaleb, Nahid; Nassiri-Kashani, Mansour; Firooz, Alireza

2011-12-01

Acne vulgaris, an inflammatory skin disease with different clinical appearances, is a common problem in most adolescents. It seems that using combinations of topical agents can decrease resistance to the treatment and improve the efficacy. Therefore, we evaluated the effects of azelaic acid (AA) 5% and clindamycin (Clin) 2% combination (AA-Clin) on mild-to-moderate acne vulgaris. The efficacy and safety of 12-week treatment with AA-Clin in patients with mild-to-moderate facial acne vulgaris were evaluated by a multicenter, randomized, and double-blind study. A total of 88 male and 62 female patients were randomly assigned to one of these treatments: AA 5%, Clin 2%, and combination of them. Every 4 weeks, total inflammatory and noninflammatory lesions were counted, acne severity index (ASI) was calculated, and patient satisfaction was recorded. Treatment for 12 weeks with combination gel significantly reduced the total lesion number compared with baseline (p < 0.01), as well as Clin 2% or AA 5% treatment groups (p < 0.05 or p < 0.01). The percentage of reduction in ASI in combination treated group (64.16 ± 6.01) was significantly more than those in the Clin 2% (47.73 ± 6.62, p < 0.05) and 5% AA (32.46 ± 5.27, p < 0.01) groups after 12 weeks. Among the patients in the AA-Clin group, 75.86% of males were satisfied or very satisfied and 85.71% of females were satisfied or very satisfied. This trend was significant in comparison to the number of patients who were satisfied with AA 5% or Clin 2% treatment (p < 0.01). Seven patients in AA-Clin group (incidence = 22%) showed adverse effects that were not statistically significant compared to treatment with individual active ingredients. The profound reduction in lesion count and ASI by combination therapy with AA-Clin gel in comparison to individual treatment with 5% AA or Clin 2% suggested the combination formula as an effective alternative in treatment of acne vulgaris.

Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004).

PubMed

Ruers, T; Punt, C; Van Coevorden, F; Pierie, J P E N; Borel-Rinkes, I; Ledermann, J A; Poston, G; Bechstein, W; Lentz, M A; Mauer, M; Van Cutsem, E; Lutz, M P; Nordlinger, B

2012-10-01

This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2-73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1-70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42-0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7-22.1) and 9.9 months (95% CI 9.3-13.7), respectively. This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain.

Volatile Compound, Physicochemical, and Antioxidant Properties of Beany Flavor-Removed Soy Protein Isolate Hydrolyzates Obtained from Combined High Temperature Pre-Treatment and Enzymatic Hydrolysis

PubMed Central

Yoo, Sang-Hun; Chang, Yoon Hyuk

2016-01-01

The present study investigated the volatile compound, physicochemical, and antioxidant properties of beany flavor-removed soy protein isolate (SPI) hydrolyzates produced by combined high temperature pre-treatment and enzymatic hydrolysis. Without remarkable changes in amino acid composition, reductions of residual lipoxygenase activity and beany flavor-causing volatile compounds such as hexanol, hexanal, and pentanol in SPI were observed after combined heating and enzymatic treatments. The degree of hydrolysis, emulsion capacity and stability, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, and superoxide radical scavenging activity of SPI were significantly increased, but the magnitudes of apparent viscosity, consistency index, and dynamic moduli (G′, G″) of SPI were significantly decreased after the combined heating and enzymatic treatments. Based on these results, it was suggested that the enzymatic hydrolysis in combination with high temperature pre-treatment may allow for the production of beany flavor-removed SPI hydrolyzates with superior emulsifying and antioxidant functionalities. PMID:28078256

Volatile Compound, Physicochemical, and Antioxidant Properties of Beany Flavor-Removed Soy Protein Isolate Hydrolyzates Obtained from Combined High Temperature Pre-Treatment and Enzymatic Hydrolysis.

PubMed

Yoo, Sang-Hun; Chang, Yoon Hyuk

2016-12-01

The present study investigated the volatile compound, physicochemical, and antioxidant properties of beany flavor-removed soy protein isolate (SPI) hydrolyzates produced by combined high temperature pre-treatment and enzymatic hydrolysis. Without remarkable changes in amino acid composition, reductions of residual lipoxygenase activity and beany flavor-causing volatile compounds such as hexanol, hexanal, and pentanol in SPI were observed after combined heating and enzymatic treatments. The degree of hydrolysis, emulsion capacity and stability, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, and superoxide radical scavenging activity of SPI were significantly increased, but the magnitudes of apparent viscosity, consistency index, and dynamic moduli (G', G″) of SPI were significantly decreased after the combined heating and enzymatic treatments. Based on these results, it was suggested that the enzymatic hydrolysis in combination with high temperature pre-treatment may allow for the production of beany flavor-removed SPI hydrolyzates with superior emulsifying and antioxidant functionalities.

Combination Drug Therapy for Pain following Chronic Spinal Cord Injury

PubMed Central

Hama, Aldric; Sagen, Jacqueline

2012-01-01

A number of mechanisms have been elucidated that maintain neuropathic pain due to spinal cord injury (SCI). While target-based therapeutics are being developed based on elucidation of these mechanisms, treatment for neuropathic SCI pain has not been entirely satisfactory due in part to the significant convergence of neurological and inflammatory processes that maintain the neuropathic pain state. Thus, a combination drug treatment strategy, wherein several pain-related mechanism are simultaneously engaged, could be more efficacious than treatment against individual mechanisms alone. Also, by engaging several targets at once, it may be possible to reduce the doses of the individual drugs, thereby minimizing the potential for adverse side effects. Positive preclinical and clinical studies have demonstrated improved efficacy of combination drug treatment over single drug treatment in neuropathic pain of peripheral origin, and perhaps such combinations could be utilized for neuropathic SCI pain. At the same time, there are mechanisms that distinguish SCI from peripheral neuropathic pain, so novel combination therapies will be needed. PMID:22550581

The application of alkaline and acidic electrolyzed water in the sterilization of chicken breasts and beef liver.

PubMed

Shimamura, Yuko; Shinke, Momoka; Hiraishi, Miki; Tsuchiya, Yusuke; Masuda, Shuichi

2016-05-01

The sterilization effect of a combination treatment with alkaline electrolyzed water (AlEW) and strong acidic electrolyzed water (StAEW) on fresh chicken breasts and beef liver was evaluated. Samples (1, 5, and 10 g) were inoculated with Salmonella Enteritidis NBRC3313, Escherichia coli ATCC 10798, Staphylococcus aureus FDA209P, and S. aureus C-29 [staphylococcal enterotoxin A (SEA) productive strain] and subjected to a dipping combination treatment (4°C and 25°C for 3 min) with AlEW and StAEW. Combination treatment with AlEW and StAEW significantly reduced the bacteria, and reduction of more than 1 log colony-forming units (CFU)/g was achieved. Furthermore, this combination treatment significantly decreased the SEA gene expression level in samples. Some quality variables of the meat samples such as pH, lipid oxidation, color, amino-acid content, texture, and sensory characteristics showed no significant differences between the combination treatment with AlEW and StAEW and the untreated control.

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

ERIC Educational Resources Information Center

Dowell, Kathy A.; Ogles, Benjamin M.

2010-01-01

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

Superior anti-tumor activity of the MDM2 antagonist idasanutlin and the Bcl-2 inhibitor venetoclax in p53 wild-type acute myeloid leukemia models.

PubMed

Lehmann, Christian; Friess, Thomas; Birzele, Fabian; Kiialainen, Anna; Dangl, Markus

2016-06-28

Venetoclax, a small molecule BH3 mimetic which inhibits the anti-apoptotic protein Bcl-2, and idasanutlin, a selective MDM2 antagonist, have both shown activity as single-agent treatments in pre-clinical and clinical studies in acute myeloid leukemia (AML). In this study, we deliver the rationale and molecular basis for the combination of idasanutlin and venetoclax for treatment of p53 wild-type AML. The effect of idasanutlin and venetoclax combination on cell viability, apoptosis, and cell cycle progression was investigated in vitro using established AML cell lines. In vivo efficacy was demonstrated in subcutaneous and orthotopic xenograft models generated in female nude or non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Mode-of-action analyses were performed by means of cell cycle kinetic studies, RNA sequencing as well as western blotting experiments. Combination treatment with venetoclax and idasanutlin results in synergistic anti-tumor activity compared with the respective single-agent treatments in vitro, in p53 wild-type AML cell lines, and leads to strongly superior efficacy in vivo, in subcutaneous and orthotopic AML models. The inhibitory effects of idasanutlin were cell-cycle dependent, with cells arresting in G1 in consecutive cycles and the induction of apoptosis only evident after cells had gone through at least two cell cycles. Combination treatment with venetoclax removed this dependency, resulting in an acceleration of cell death kinetics. As expected, gene expression studies using RNA sequencing showed significant alterations to pathways associated with p53 signaling and cell cycle arrest (CCND1 pathway) in response to idasanutlin treatment. Only few gene expression changes were observed for venetoclax treatment and combination treatment, indicating that their effects are mediated mainly at the post-transcriptional level. Protein expression studies demonstrated that inhibition of the anti-apoptotic protein Mcl-1 contributed to the activity of venetoclax and idasanutlin, with earlier inhibition of Mcl-1 in response to combination treatment contributing to the superior combined activity. The role of Mcl-1 was confirmed by small hairpin RNA gene knockdown studies. Our findings provide functional and molecular insight on the superior anti-tumor activity of combined idasanutlin and venetoclax treatment in AML and support its further exploration in clinical studies.

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.

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells.

PubMed

Al-Qatati, Abeer; Aliwaini, Saeb

2017-12-01

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma.

Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells

PubMed Central

Al-Qatati, Abeer; Aliwaini, Saeb

2017-01-01

Melanoma is an aggressive skin cancer and its incidence is increasing faster than any other type of cancer. Whilst dacarbazine (DTIC) is the standard chemotherapy for metastatic melanoma, it has limited success. Statins, including pitavastatin, have been demonstrated to have a range of anti-cancer effects in a number of human cancer cell lines. The present study therefore explored the anti-cancer activity of combined DTIC and pitavastatin in A375 and WM115 human melanoma cells. Cell survival assays demonstrated that combined DTIC and pitavastatin treatment resulted in synergistic cell death. Cell cycle analyses further revealed that this combined treatment resulted in a G1 cell cycle arrest, as well as a sub-G1 population, indicative of apoptosis. Activation of apoptosis was confirmed by Annexin V-fluorescein isothiocyanate/propidium iodide double-staining and an increase in the levels of active caspase 3 and cleaved poly (ADP-ribose) polymerase. Furthermore, it was demonstrated that apoptosis occurs through the intrinsic pathway, evident from the release of cytochrome c. Finally, combined DTIC and pitavastatin treatment was demonstrated to also activate autophagy as part of a cell death mechanism. The present study provides novel evidence to suggest that the combined treatment of DTIC and pitavastatin may be effective in the treatment of melanoma. PMID:29344241

40 CFR 141.718 - Treatment performance toolbox components.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for.... (a) Combined filter performance. Systems using conventional filtration treatment or direct filtration... the criteria in this paragraph. Combined filter effluent (CFE) turbidity must be less than or equal to...

40 CFR 141.718 - Treatment performance toolbox components.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for.... (a) Combined filter performance. Systems using conventional filtration treatment or direct filtration... the criteria in this paragraph. Combined filter effluent (CFE) turbidity must be less than or equal to...

40 CFR 141.718 - Treatment performance toolbox components.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced Treatment for.... (a) Combined filter performance. Systems using conventional filtration treatment or direct filtration... the criteria in this paragraph. Combined filter effluent (CFE) turbidity must be less than or equal to...

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 Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation

PubMed Central

Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group (n = 35) and control group (n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group (P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups (P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications. PMID:29785195

Combined Therapies of Modified Taiyi Miraculous Moxa Roll and Cupping for Patients with Lumbar Intervertebral Disc Herniation.

PubMed

Cai, Chunyue; Gong, Yuefeng; Dong, Dayong; Xue, Jinbiao; Zheng, Xiaoting; Zhong, Zhangfeng; Shao, Jialong; Mi, Daguo

2018-01-01

Lumbar intervertebral disc herniation is a kind of syndrome caused by stimulation or pressure of nerve root and cauda equina due to intervertebral disc disorder, fibrous ring rupture, and pulpiform nucleus protrusion. Application of traditional Chinese medicine (TCM) including acupuncture therapy and cupping therapy is unique and effective treatment for lumbar intervertebral disc herniation in China. Hence, we try to investigate the combined clinical efficacy of modified Taiyi miraculous moxa roll and cupping therapy on patients with lumbar intervertebral disc herniation. Seventy patients were randomly assigned into combined treatment group ( n = 35) and control group ( n = 35). The treatment group received combined therapy of modified Taiyi miraculous moxa roll and cupping therapy, while control group received acupuncture therapy alone. Diagnostic criteria of TCM syndrome, Japanese Orthopedic Association (JOA) score, and simplified McGill pain questionnaire (MPQ) were used to evaluate the therapy. 11 and 13 out of 35 subjects in the combined treatment group had improvement > 75% and between 50% and 75%, respectively. The corresponding number was 2 and 22 of 35 subjects in the acupuncture group. There was significant difference in the clinical efficacy between the treatment group and control group ( P = 0.036). The scores of JOA and MPQ detected in the patients of the two groups ( P < 0.05) also showed statistically significant differences. Moreover, no serious adverse events occurred in the patients, who received cupping therapy or acupuncture. The combined or alone therapies can effectively improve the treatment efficacy in the patients with lumbar intervertebral disc herniation, while the combined therapies show more comparative effectiveness. Furthermore, the combined therapies are potentially safe and cost-effective and also benefit the improvement of short-term pain. Therefore, the combined therapies of the two ancient TCM deserve further clinical applications.

The combined mode of action of fipronil and amitraz on the motility of Rhipicephalus sanguineus.

PubMed

Prullage, Joseph B; Tran, Hai V; Timmons, Phil; Harriman, Jay; Chester, S Theodore; Powell, Kerrie

2011-07-15

The motility of adult Rhipicephalus sanguineus was evaluated subsequent to treatments of amitraz, fipronil and the combination of fipronil plus amitraz against a vehicle control in a Petri dish assay using the LemnaTec Scanalyzer Imaging System. The assay was run using a fixed dilution of amitraz (0.32μg/cm(2)); serial dilutions of fipronil (1.3, 0.33, 0.08, 0.02, or 0.005μg/cm(2)); and the same serial dilutions of fipronil in combination with the fixed dilution of amitraz. Measurement of motility was made of unstimulated ticks and then after stimulation at 1, 4, 18-22, and 24h post exposure (hpe) of the Petri dishes. For the unstimulated ticks, there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. However, these two treatment groups had significantly higher motility than the solvent control and fipronil treatment groups. The unstimulated ticks in the amitraz treatment group had significantly higher motility than the fipronil plus amitraz treatment group at the later time points. Measurements after stimulation demonstrated there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. By 18 hpe, the fipronil plus amitraz treatment group had significantly lower motility than all other treatment groups and at 21-22 and 24 hpe the other treatment groups did not differ from the control group. The action could be divided in two phases in the combination experiment: phase 1: an early increase in motility due to amitraz is identified in both amitraz alone or fipronil plus amitraz groups; phase 2: the combination of fipronil plus amitraz caused a significantly greater reduction in motility, suggesting mortality of the ticks, compared to fipronil or amitraz alone. These results demonstrate a synergism resulting from the combination of fipronil plus amitraz. Copyright © 2011 Elsevier B.V. All rights reserved.

Combined effects of high pressure and sodium hydrogen carbonate treatment on beef: improvement of texture and color

NASA Astrophysics Data System (ADS)

Ohnuma, Shun; Kim, Yun-Jung; Suzuki, Atsushi; Nishiumi, Tadayuki

2013-06-01

We investigated the effect of combined high pressure and sodium hydrogen carbonate (NaHCO3) treatment on the physical properties and color of silverside Australian beef. Meat samples were pressurized at 100-500 MPa and the water content, weight reduction, rupture stress, and meat color were determined. The water content of meat treated with NaHCO3 and high pressure (300 MPa) reached a maximum of 70.1%. Weight reduction tended to decrease with high pressure treatment at 300 MPa. Meats treated with NaHCO3 and high pressure at 400 MPa showed a>50% decrease in hardness. Whitening of the meat was reduced by the combined high pressure and NaHCO3 treatment. Therefore, the combined high pressure and NaHCO3 treatment is effective for improvement of beef quality.

[Clinicofunctional condition and quality of life in patients with chronic obstructive pulmonary disease before and after outpatient treatment with fenspiride].

PubMed

Butorov, S I; Butorov, I V; Bodrug, N I; Krushka, S I; Tofan, E F

2008-01-01

To study effects of long-term administration of fenspiride in combination with broncholytic drugs on dynamics of clinical symptoms, external respiration function and quality of life in patients with chronic obstructive pulmonary disease (COPD). A comparative randomized trial of fenspiride used for 6 months in combination with broncholytic drugs enrolled 68 COPD patients. A clinical status, external respiration function were examined. Quality of life was evaluated with WHO questionnaire WHOQOL-100. Addition of fenspiride to combined treatment of COPD attenuates COPD symptoms, normalizes blood biochemistry, improves external respiration function, raises exercise tolerance. Quality of life improved by physical and mental state scales. Fenspiride addition to COPD treatment improves efficacy of the standard treatment and is recommended for treatment of COPD of stage I and II in combination with broncholytic drugs.

[Therapeutic effect of extracorporeal shock wave combined with orthopaedic insole on plantar fasciitis].

PubMed

Yan, Wenguang; Sun, Shaodan; Li, Xuhong

2014-12-01

To observe the therapeutic effect of extracorporeal shock wave combined with orthopaedic insole on plantar fasciitis. A total of 153 plantar with plantar fasciitis were randomly divided into a combined group (n=51), an extracorporeal shock wave group (n=53) and an orthopaedic group (n=49). The combined group received treatment of both extracorporeal shock wave and orthopaedic insole while the extracorporeal shock wave or the orthopaedic group only received the treatment of extracorporeal shock wave or orthopaedic insole. The therapeutic parameters such as visual analogue scale (VAS) scores, continued walking time and thickness of the plantar fascia were monitored before and aft er the treatment for 2 weeks, 1 month and 3 months, respectively. The VAS scores in the 3 groups were all reduced after the treatment compared with the corresponding scores before the therapy (P< 0.05). The VAS score in the extracorporeal shock wave group was greater than that in the orthopedic group after the treatment for 2 weeks. The VAS score in the combined group was smaller than that in the orthopedic group after the treatment for 2 weeks and 3 months (P< 0.05). The VAS scores in the orthopedic group and the combined group were smaller than those in the extracorporeal shock wave group after the treatment for 1 month or 3 months (P< 0.05). The continued walking time and thickness of the plantar fascia was improved after the treatment (P< 0.05). The cure rate and total effective rate in the combination group were obviously greater than those in the two other groups. The cure rate in the orthopedic group was greater than that in the extracorporeal shock wave group (P< 0.05). Extracorporeal shock wave combined with orthopaedic insole therapy is an effective method to treat plantar fasciitis. It is recommended to spread in clinic.

Challenges in the Treatment of Major Depressive Disorder With Psychotic Features

PubMed Central

Rothschild, Anthony J.

2013-01-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments. PMID:23599251

Challenges in the treatment of major depressive disorder with psychotic features.

PubMed

Rothschild, Anthony J

2013-07-01

Psychotic depression is associated with significant morbidity and mortality but is underdiagnosed and undertreated. In recent years, there have been several studies that have increased our knowledge regarding the optimal treatment of patients with psychotic depression. The combination of an antidepressant and antipsychotic is significantly more effective than either antidepressant monotherapy or antipsychotic monotherapy for the acute treatment of psychotic depression. Most treatment guidelines recommend either the combination of an antidepressant with an antipsychotic or ECT for the treatment of an acute episode of unipolar psychotic depression. The optimal maintenance treatment after a person responds to either the antidepressant/antipsychotic combination or the ECT is unclear particularly as it pertains to length of time the patient needs to take the antipsychotic medication. Little is known regarding the optimal treatment of a patient with bipolar disorder who has an episode of psychotic depression or the clinical characteristics of responders to medication treatments vs ECT treatments.

Impact of drug classes and treatment availability on the rate of antiretroviral treatment change in the TREAT Asia HIV Observational Database (TAHOD)

PubMed Central

Srasuebkul, Preeyaporn; Calmy, Alexandra; Zhou, Jialun; Kumarasamy, Nagalingeswaran; Law, Matthew; Lim, Poh Lian

2007-01-01

Background It is critical to understand the pattern of antiretroviral treatment (ART) prescription in different regions of the world as ART procurement needs to be anticipated. We aimed at exploring rates and predictors of ART combination changes in clinical practice in Treat Asia HIV Observational Database (TAHOD). Methods Rates of ART changes were examined in patients who started first line triple or more ART combination in TAHOD, and had at least one follow-up visit. Rates of ART changes were summarised per follow-up year, and factors associated with changes assessed using random-effect Poisson regression. The Kaplan-Meier method was used to determine durations of patients in their first, second and third regimen. Results A total of 1846 patients initiated an ART combination with at least three drugs. Median follow up time for the first treatment was 3.2 years. The overall rate of ART change was 29 per 100-person-year. In univariate analyses, rate of treatment change was significantly associated with exposure category, the country income category, the drug class combination, calendar year and the number of combinations. In multivariate analysis, compared to d4T/3TC/NVP, starting ART with another NNRTI-containing regimen, with PI only or with a triple NRTI regimen was associated with a higher risk of combination change (relative risk (RR) 1.6 (95% CI 1.64 – 1.96), p < 0.001, RR 3.39 (2.76 – 4.16) p < 0.001, RR 6.37 (4.51 – 9.00), p < 0.001). Being on a second or a third combination regimen was also associated with a decreased rate of ART change, compared with first ART combination (RR 0.82 (0.68 – 0.99), p = 0.035, RR 0.77 (0.61 – 0.97), p = 0.024). Sites with fewer than 12 drugs used had an increased rate of treatment changes (1.31 (1.13 – 1.51), p < 0.001). Injecting drug users, and other/unknown exposure was found to increase rate of treatment change (1.24 (1.00 – 1.54), p = 0.055). Percentages of patients who stopped treatment due to adverse events were 31, 27 and 32 in 1st, 2nd and 3rd treatment combinations, respectively. Conclusion Our study suggests that drug availability impacts on ART prescription patterns. Our data, reflecting real clinic use in Asia, suggest that around half of all patients require second combination ART by 3 years after treatment initiation. PMID:17868478

[Posterior capsule opacification, capsular bag distension syndrome, and anterior capsular phimosis: A retrospective cohort study].

PubMed

González-Martín-Moro, J; González-López, J J; Gómez-Sanz, F; Zarallo-Gallardo, J; Cobo-Soriano, R

2015-02-01

To determine the incidence and the risk factors involved in the development of the three main postoperative capsular complications: posterior capsule opacification (PCO), capsular bag distension syndrome (CBDS), and anterior capsular phimosis syndrome (ACP). A retrospective cohort study was conducted on 801 patients submitted to cataract surgery in the ophthalmology unit of Hospital del Henares (Madrid) from March 2, 2009 to February 28, 2010. Computerized clinical charts were reviewed during July 2012. PCO was studied using the Kaplan-Meier method (log rank test). A total of 167 patients developed PCO. No association could be demonstrated between PCO and age, sex, diabetes mellitus, phaco technique, IOL model, tamsulosin intake, glaucoma, and age-related macular degeneration. Three patients developed CBDS, all of them have received and Akreos Adapt AO(®) (Bausch & Lomb). Two of them were young men who had received surgery for posterior subcapsular cataracts. Three patients developed ACP, 2 of whom had received a MicroSlim(®) IOL (PhysIOL). No association was found between PCO and any of the studied variables. Male gender, young age, subcapsular cataract and large non-angulated lens such as Akreos Adapt AO(®) could be associated with CBDS. ACP could be more frequent when microincision IOLs (like MicroSlim(®)) are implanted. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Gateways to Clinical Trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2002-09-01

Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies knowledge area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Adalimumab, aeroDose insulin inhaler, agomelatine, alendronic acid sodium salt, aliskiren fumarate, alteplase, amlodipine, aspirin, atazanavir; Bacillus Calmette-Guérin, basiliximab, BQ-788, bupropion hydrochloride; Cabergoline, caffeine citrate, carbamazepine, carvedilol, celecoxib, cyclosporine, clopidogrel hydrogensulfate, colestyramine; Dexamethasone, diclofenac sodium, digoxin, dipyridamole, docetaxel, dutasteride; Eletriptan, enfuvirtidie, eplerenone, ergotamine tartrate, esomeprazole magnesium, estramustine phosphate sodium; Finasteride, fluticasone propionate, fosinopril sodium; Ganciclovir, GBE-761-ONC, glatiramer acetate, gliclazide, granulocyte-CSF; Heparin sodium, human isophane insulin (pyr), Hydrochlorothiazide; Ibuprofen, inhaled insulin, interferon alfa, interferon beta-1a; Laminvudine, lansoprazole, lisinopril, lonafarnib, losartan potassium, lumiracoxib; MAb G250, meloxicam methotrexate, methylprednisolone aceponate, mitomycin, mycophenolate mofetil; Naproxen sodium, natalizumab, nelfinavir mesilate, nemifitide ditriflutate, nimesulide; Omalizumab, omapatrilat, omeprazole, oxybutynin chloride; Pantoprazole sodium, paracetamol, paroxetine, pentoxifylline, pergolide mesylate, permixon, phVEGF-A165, pramipexole hydrochloride, prasterone, prednisone, probucol, propiverine hydrochloride; Rabeprazole sodium, resiniferatoxin, risedronate sodium, risperidone, rofecoxib rosiglitazone maleate, ruboxistaurin mesilate hydrate; Selegiline transdermal system, sertraline, sildenafil citrate, streptokinase; Tadalafil, tamsulosin hydrochloride, technosphere/Insulin, tegaserod maleate, tenofovir disoproxil fumarate, testosterone heptanoate, testosterone undecanoate, tipifarnib, tolterodine tartrate, topiramate, troglitazone; Ursodeoxycholic acid; Valdecoxib, valsartan, vardenafil, venlafaxine hydrochloride, VX-745.

Desloratadine and pseudoephedrine combination therapy as a comprehensive treatment for allergic rhinitis and nasal congestion.

PubMed

Anolik, Robert

2009-06-01

Allergic rhinitis (AR) is rapidly increasing in global prevalence. Symptoms of AR, particularly nasal congestion, can cause quality of life (QoL) impairment. Second-generation antihistamines are a recommended first-line therapy for AR but are not viewed as very effective for the treatment of congestion. Therefore, an antihistamine plus a decongestant, such as the combination of desloratadine and pseudoephedrine, is a convenient and efficacious treatment. To review the clinical evidence on the efficacy and safety of combination desloratadine/pseudoephedrine for the treatment of AR symptoms, particularly nasal congestion. Four large studies found that improvement in nasal congestion is enhanced when patients are treated with combination desloratadine/pseudoephedrine. The combination drug significantly improved mean reflective nasal congestion scores in these studies compared with either component as monotherapy (p

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

Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria/caspase-mediated pathway in HeLa cells.

PubMed

Youn, Myung-Ja; So, Hong-Seob; Cho, Hea-Joong; Kim, Hyung-Jin; Kim, Yunha; Lee, Jeong-Han; Sohn, Jung Sook; Kim, Yong Kyu; Chung, Sang-Young; Park, Raekil

2008-05-01

Berberine, a main component of Coptidis Rhizoma, has been extensively studied and is known to exhibit multiple pharmacologic activities. In this study, we investigated whether the combination of berberine and cisplatin exhibited significant cytotoxicity in HeLa cells. Apoptosis was evaluated based on DNA fragmentation and cytofluorometrically with the annexin-V/propidium iodide labeling method. Combined treatment with berberine and cisplatin acted in concert to induce loss of mitochondrial membrane potential (Delta Psi m), release of cytochrome-c from mitochondria, and decreased expression of antiapoptotic Bcl-2, Bcl-x/L, resulting in activation of caspases and apoptosis. Further study showed that cell death induced by the combined treatment was associated with increased reactive oxygen species generation and lipid peroxidation. Moreover, we discovered that the combined treatment-induced apoptosis was mediated by the activation of the caspase cascade. These results indicated that the potential of cytotoxicity mediated through the mitochondria-caspase pathway is primarily involved in the combined treatment-induced apoptosis.

Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo.

PubMed

Li, Li; Li, Lu; Wu, Yan; Gao, Xing-Hua; Chen, Hong-Duo

2016-06-01

Vitiligo is an acquired depigmenting disease with uncertain etiopathogenesis and the treatment modalities need to be consistently updated. To evaluate a triple-combination treatment with oral α-lipoic acid (ALA), betamethasone injection, and narrowband ultraviolet B (NB-UVB) on vitiligo. Patients with non-segmental and progressive vitiligo lesions were randomly assigned to two groups. The treatment group and the control group were respectively treated with oral ALA and placebo, in combination with betamethasone injection and NB-UVB. The effectiveness and adverse events were evaluated by investigators and patients before and after treatment. Fifty non-segmental progressive vitiligo patients were enrolled in the study. The treatment period was 6 months. In treatment group, over 40% patients achieved > 50% improvement and ≥ 5 satisfaction score by 3-month therapy (M3). This percentage increased to 90% at M6. Treatment group achieved better efficacy than control group at M3, while no difference was seen at M6. The combined treatment with oral ALA, betamethasone injection, and NB-UVB was effective and safe on non-segmental progressive vitiligo. ALA could accelerate the initial response of repigmentation.

Evaluation of the efficacy and safety of bi-daily combination therapy with pyridoxine and doxylamine for nausea and vomiting of pregnancy.

PubMed

Ashkenazi-Hoffnung, Liat; Merlob, Paul; Stahl, Bracha; Klinger, Gil

2013-01-01

Diclectin (pyridoxine 10 mg and doxylamine 10 mg) has traditionally been used to treat nausea and vomiting of pregnancy (NVP); however, this drug is unavailable in many countries. To evaluate the efficacy and safety of a simple bi-daily treatment regimen with the combination of pyridoxine (50 mg twice daily) and doxylamine (25-50 mg) as an alternative treatment for NVP. A prospective case-controlled observational study of mother-infant pairs was conducted between February 2008 and December 2010. All women who contacted the Beilinson Teratology Information Service (BELTIS) regarding treatment of NVP were eligible for inclusion. Using data on NVP severity, treatment efficacy and outcomes, we compared the two groups of women: those treated with the combination of pyridoxine and doxylamine (treatment group, n=29) and those treated with metoclopramide (control group, n=29). Moderate to severe symptoms were present in 97% of the treatment group women vs. 69% of control group women (P < 0.01). Despite increased symptom severity in the treatment group, the combination regimen was efficacious: 20/29 (69%) vs. 18/25 (72%) in the treatment vs. control women respectively (P = 0.65). There were no congenital anomalies in the treatment group. Follow-up was normal for all infants. Bi-daily combination therapy with pyridoxine and doxylamine for NVP is safe, has comparable efficacy to metoclopramide, and is a treatment alternative in countries where Diclectin is not available. Despite symptoms warranting counseling by a teratology information service, more than a third of women do not take the suggested treatment.

Opportunities for Combined Heat and Power at Wastewater Treatment Facilities: Market Analysis and Lessons from the Field

EPA Pesticide Factsheets

This report presents the opportunities for combined heat and power (CHP) applications in the municipal wastewater treatment sector, and it documents the experiences of the wastewater treatment facility (WWTF) operators who have employed CHP.

Efficacy of Clarithromycin-Naproxen-Oseltamivir Combination in the Treatment of Patients Hospitalized for Influenza A(H3N2) Infection: An Open-label Randomized, Controlled, Phase IIb/III Trial.

PubMed

Hung, Ivan F N; To, Kelvin K W; Chan, Jasper F W; Cheng, Vincent C C; Liu, Kevin S H; Tam, Anthony; Chan, Tuen-Ching; Zhang, Anna Jinxia; Li, Patrick; Wong, Tin-Lun; Zhang, Ricky; Cheung, Michael K S; Leung, William; Lau, Johnson Y N; Fok, Manson; Chen, Honglin; Chan, Kwok-Hung; Yuen, Kwok-Yung

2017-05-01

Influenza causes excessive hospitalizations and deaths. The study assessed the efficacy and safety of a clarithromycin-naproxen-oseltamivir combination for treatment of serious influenza. From February to April 2015, we conducted a prospective open-label, randomized, controlled trial. Adult patients hospitalized for A(H3N2) influenza were randomly assigned to a 2-day combination of clarithromycin 500 mg, naproxen 200 mg, and oseltamivir 75 mg twice daily, followed by 3 days of oseltamivir or to oseltamivir 75 mg twice daily without placebo for 5 days as a control method (1:1). The primary end point was 30-day mortality. The secondary end points were 90-day mortality, serial nasopharyngeal aspirate (NPA) virus titer, percentage of neuraminidase-inhibitor-resistant A(H3N2) virus (NIRV) quasispecies, pneumonia severity index (PSI), and duration of hospital stay. Among the 217 patients with influenza A(H3N2) enrolled, 107 were randomly assigned to the combination treatment. The median age was 80 years, and 53.5% were men. Adverse events were uncommon. Ten patients died during the 30-day follow-up. The combination treatment was associated with lower 30-day mortality (P = .01), less frequent high dependency unit admission (P = .009), and shorter hospital stay (P < .0001). The virus titer and PSI (days 1-3; P < .01) and the NPA specimens with NIRV quasispecies ≥ 5% (days 1-2; P < .01) were significantly lower in the combination treatment group. Multivariate analysis showed that combination treatment was the only independent factor associated with lower 30-day mortality (OR, 0.06; 95% CI, 0.004-0.94; P = .04). Combination treatment reduced both 30- and 90-day mortality and length of hospital stay. Further study of the antiviral and immunomodulatory effects of this combination treatment of severe influenza is warranted. BioMed Central; No.: ISRCTN11273879 DOI 10.1186/ISRCTN11273879; URL: www.isrctn.com/ISRCTN11273879. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin.

PubMed

Mibielli, Marco Antonio; Nunes, Carlos Pereira; Cohen, José Carlos; Scussel, Ari Boulanger; Higashi, Rafael; Bendavit, Gabriel Gherman; Oliveira, Lisa; Geller, Mauro

2010-01-01

This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + uridine + cytidine + vitamin B12 (Group DN, n=40) or uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.

Effect of sanhuangwuji powder, anti-rheumatic drugs, and ginger-partitioned acupoint stimulation on the treatment of rheumatoid arthritis with peptic ulcer: a randomized controlled study.

PubMed

Liu, Defang; Guo, Mingyang; Hu, Yonghe; Liu, Taihua; Yan, Jiao; Luo, Yong; Yun, Mingdong; Yang, Min; Zhang, Jun; Guo, Linglin

2015-06-01

To observe the efficacy and safety of oral sanhuangwuji powder, anti-rheumatic drugs (ARDs), and ginger-partitioned acupoint stimulation at zusanli (ST 36) on the treatment of rheumatoid arthritis (RA) complicated by peptic ulcer. This prospective randomized controlled study included 180 eligible inpatients and outpatients randomly assigned to an ARD treatment (n.= 60), ginger-partitioned stimulation (n = 60), or combination treatment (n = 60). Patients assigned to the ARD group were given oral celecoxib, methotrexate, and esomeprazole. Patients assigned to the ginger-partitioned stimulation group were given ginger-partitioned acupoint stimulation at zusanli (ST 36) in addition to the ARDs. Patients in the combination treatment group were given oral sanhuangwuji powder, ginger-partitioned acupoint stimulation at susanli (ST 36), and ARDs. All patients were followed up for 2 months to evaluate clinical effects and safety. The study was registered in the World Health Organization database at the General Hospital of Chengdu Military Area Command Chinese People's Liberation Army (ChiCTR-TCC12002824). The combination treatment group had significantly greater improvements in RA symptoms, laboratory outcomes, and gastrointestinal symptom scores, compared with the other groups (P < 0.05). The peptic ulcer healing rate in the combination treatment group was significantly greater than that in the ARD treatment group (χ2= 16.875, P < 0.05) and the ginger-partitioned stimulation group (χ2= 6.171, P < 0.05). Combination treatment with ginger-partitioned acupoint stimulation at zusanli (ST 36), oral sanhuangwuji powder, and ARDs had a better clinical effect for RA with complicated peptic ulcer, compared with ARD treatmentalone or in combination with ginger-partitioned acupoint stimulation.

Combined effects of lanthanum(III) and elevated ultraviolet-B radiation on root growth and ion absorption in soybean seedlings.

PubMed

Huang, Guang Rong; Wang, Li Hong; Zhou, Qing

2014-03-01

Rare earth element accumulation in the soil and elevated ultraviolet (UV)-B radiation (280-315 nm) are important environmental issues worldwide. To date, there have been no reports concerning the combined effects of lanthanum (La)(III) and elevated UV-B radiation on plant roots in regions where the two issues occur simultaneously. Here, the combined effects of La(III) and elevated UV-B radiation on the growth, biomass, ion absorption, activities, and membrane permeability of roots in soybean (Glycine max L.) seedlings were investigated. A 0.08 mmol L(-1) La(III) treatment improved the root growth and biomass of soybean seedlings, while ion absorption, activities, and membrane permeability were obviously unchanged; a combined treatment with 0.08 mmol L(-1) La(III) and elevated UV-B radiation (2.63/6.17 kJ m(-2) day(-1)) exerted deleterious effects on the investigated indices. The deleterious effects were aggravated in the other combined treatments and were stronger than those of treatments with La(III) or elevated UV-B radiation alone. The combined treatment with 0.24/1.20 mmol L(-1) La(III) and elevated UV-B radiation exerted synergistically deleterious effects on the growth, biomass, ion absorption, activities, and membrane permeability of roots in soybean seedlings. In addition, the deleterious effects of the combined treatment on the root growth were due to the inhibition of ion absorption induced by the changes in the root activity and membrane permeability.

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells

PubMed Central

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells. PMID:23818927

Decursin and Doxorubicin Are in Synergy for the Induction of Apoptosis via STAT3 and/or mTOR Pathways in Human Multiple Myeloma Cells.

PubMed

Jang, Jinsil; Jeong, Soo-Jin; Kwon, Hee-Young; Jung, Ji Hoon; Sohn, Eun Jung; Lee, Hyo-Jung; Kim, Ji-Hyun; Kim, Sun-Hee; Kim, Jin Hyoung; Kim, Sung-Hoon

2013-01-01

Background. Combination cancer therapy is one of the attractive approaches to overcome drug resistance of cancer cells. In the present study, we investigated the synergistic effect of decursin from Angelica gigas and doxorubicin on the induction of apoptosis in three human multiple myeloma cells. Methodology/Principal Findings. Combined treatment of decursin and doxorubicin significantly exerted significant cytotoxicity compared to doxorubicin or decursin in U266, RPMI8226, and MM.1S cells. Furthermore, the combination treatment enhanced the activation of caspase-9 and -3, the cleavage of PARP, and the sub G1 population compared to either drug alone in three multiple myeloma cells. In addition, the combined treatment downregulated the phosphorylation of mTOR and its downstream S6K1 and activated the phosphorylation of ERK in three multiple myeloma cells. Furthermore, the combined treatment reduced mitochondrial membrane potential, suppressed the phosphorylation of JAK2, STAT3, and Src, activated SHP-2, and attenuated the expression of cyclind-D1 and survivin in U266 cells. Conversely, tyrosine phosphatase inhibitor pervanadate reversed STAT3 inactivation and also PARP cleavage and caspase-3 activation induced by combined treatment of doxorubicin and decursin in U266 cells. Conclusions/Significance. Overall, the combination treatment of decursin and doxorubicin can enhance apoptotic activity via mTOR and/or STAT3 signaling pathway in multiple myeloma cells.

Comparison of the safety and efficacy of a fixed-dose combination regimen and separate formulations for pulmonary tuberculosis treatment.

PubMed

Wu, Jiun-Ting; Chiu, Chien-Tung; Wei, Yu-Feng; Lai, Yung-Fa

2015-06-01

Fixed-dose combination formulations, which simplify the administration of drugs and prevent the development of drug resistance, have been recommended as a standard anti-tuberculosis treatment regimen. However, the composition and dosage recommendations for fixed-dose combination formulations differ from those for separate formulations. Thus, questions about the effectiveness and side effects of combination formulations remain. The aim of this study was to compare the safety and efficacy of these two types of anti-tuberculosis regimens for pulmonary tuberculosis treatment. A prospective, randomized controlled study was conducted using the directly observed treatment short-course strategy. Patients were randomly allocated to one of two short-course regimens. One year after completing the treatment, these patients' outcomes were analyzed. ClinicalTrials.gov: NCT00979290. A total of 161 patients were enrolled, 142 of whom were evaluable for safety assessment. The two regimens had a similar incidence of adverse effects. In the per-protocol population, serum bilirubin concentrations at the peak level, at week 4, and at week 8 were significantly higher for the fixed-dose combination formulation than for the separate formulations. All patients had negative sputum cultures at the end of the treatment, and no relapse occurred after one year of follow-up. In this randomized study, transient higher serum bilirubin levels were noted for the fixed-dose combination regimen compared with the separate formulations during treatment. However, no significant difference in safety or efficacy was found between the groups when the directly observed treatment short-course strategy was used.

Remission of acromegaly after treatment withdrawal in patients controlled by cabergoline alone or in combination with octreotide: results from a multicenter study.

PubMed

Casagrande, A; Bronstein, M D; Jallad, R S; Mota, J I; Tabet, A; Abucham, J

2017-05-01

Remission of acromegaly has been reported after somatostatin analogs withdrawal, but not after withdrawal of combination therapy with cabergoline, and only in case reports of patients controlled by cabergoline alone. To establish the remission rates (normal IGF-1 for age/sex: IGF-1 ≤ 1.00 xULN) after withdrawal of combined treatment with octreotide LAR and cabergoline and of cabergoline alone, we prospectively studied 16 patients with acromegaly controlled by those treatments in the preceding 2 years as part of a larger study on remission of acromegaly after withdrawal of different medical treatments. Among 97 patients with controlled acromegaly included in the entire study, only 16 patients had been on combination therapy (n = 12) or cabergoline alone (n = 4). At 8 weeks after treatment withdrawal, three patients (19%) were in remission (short-term remission). At 60 weeks (long-term remission), IGF-1 levels were still in the normal range in two patients (12.5%) and remained normal up to 108 weeks after treatment withdrawal (last visit). One patient had been treated with cabergoline alone and another one with combination of octreotide and cabergoline before treatment withdrawal. Remission of acromegaly after treatment withdrawal seems to be uncommon in patients controlled by cabergoline, either as monotherapy or in combination with octreotide. In the future, larger studies and/or meta-analysis will be necessary to accurately establish the remission rates of acromegaly after withdrawal of cabergoline with or without somatostatin analogs.

Comparative efficacy, acceptability, and safety of medicinal, cognitive-behavioral therapy, and placebo treatments for acute major depressive disorder in children and adolescents: a multiple-treatments meta-analysis.

PubMed

Ma, Dongfeng; Zhang, Zhijun; Zhang, Xiangrong; Li, Lingjiang

2014-06-01

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few comprehensive studies compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in pediatric patients. Multiple-treatments meta-analysis (MTM) was conducted to assess efficacy, acceptability, and safety of contemporary interventions in children and adolescents with MDD. Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO, PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for randomized controlled trials (RCTs) comparing medicinal interventions (citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline, venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT, and placebo treatment for acute MDD from January 1988 to March 2013. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Bayesian methods were used to conduct a MTM including age and funding subgroups. A total of 21 RCTs (4969 participants) were identified. Combined fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment. Sertraline, paroxetine, escitalopram, and venlafaxine showed superior acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT combination was less safe, though CBT was safer than fluoxetine alone. Combined fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy; sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated; and mirtazapine and venlafaxine were the safest. Sertraline and mirtazapine exhibited optimally balanced efficacy, acceptability, and safety for first-line acute treatment of child and adolescent MDD.

Association between Gastrointestinal Illness and Precipitation in Areas Impacted by Combined Sewer Systems: Utilizing a Distributed Lag Model

EPA Science Inventory

Combined sewer systems collect rainwater runoff, sewage, and industrial wastewater for transit to treatment facilities. With heavy precipitation, volumes can exceed capacity of treatment facilities, and wastewater discharges directly to receiving waters. These combined sewer over...

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

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

Schuuring, Janneke; Department of Neurology, Groene Hart Hospital, Gouda; Bussink, Johan

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, whenmore » combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.« less

A combination of He-Ne laser irradiation and exogenous NO application efficiently protect wheat seedling from oxidative stress caused by elevated UV-B stress.

PubMed

Li, Yongfeng; Gao, Limei; Han, Rong

2016-12-01

The elevated ultraviolet-B (UV-B) stress induces the accumulation of a variety of intracellular reactive oxygen species (ROS), which seems to cause oxidative stress for plants. To date, very little work has been done to evaluate the biological effects of a combined treatment with He-Ne laser irradiation and exogenous nitric oxide (NO) application on oxidative stress resulting from UV-B radiation. Thus, our study investigated the effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative damages in wheat seedlings under elevated UV-B stress. Our data showed that the reductions in ROS levels, membrane damage parameters, while the increments in antioxidant contents and antioxidant enzyme activity caused by a combination with He-Ne laser and exogenous NO treatment were greater than those of each individual treatment. Furthermore, these treatments had a similar effect on transcriptional activities of plant antioxidant enzymes. This implied that the protective effects of a combination with He-Ne laser irradiation and exogenous NO treatment on oxidative stress resulting from UV-B radiation was more efficient than each individual treatment with He-Ne laser or NO molecule. Our findings might provide beneficial theoretical references for identifying some effective new pathways for plant UV-B protection.

Efficacy of fipronil, amitraz and (S)-methoprene combination spot-on for dogs against adult dog fleas (Ctenocephalides canis, Curtis, 1826).

PubMed

Bouhsira, Emilie; Yoon, Stephen S; Roques, Martine; Manavella, Coralie; Vermot, Solange; Cramer, Luiz G; Ollagnier, Catherine; Franc, Michel

2011-07-15

A novel spot-on formulation combining fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) was evaluated in adult Beagle dogs in a study to determine its adulticidal efficacy against the dog flea (Ctenocephalides canis, Curtis, 1826). Sixteen dogs were randomly allocated to treatment groups: 8 dogs served as untreated controls, and 8 dogs were treated once. Treatment consisted of applying a new combination formulation to deliver at least 6.7mg fipronil/kg body weight (bw), 8.0mg amitraz/kg bw, and 6.0mg (S)-methoprene/kg bw. The combination was designed to enhance the efficacy against ticks of the original fipronil/(S)-methoprene combination. Each dog was infested with 100 adult unfed dog fleas within 24h prior to treatment and then at weekly intervals for 8 weeks after treatment. At 24h after treatment or after each subsequent infestation, each dog was combed thoroughly to remove live fleas to be counted. A single treatment with CERTIFECT provided excellent knock-down of fleas within 24h after treatment and controlled re-infestations for up to 7 weeks (efficacy ≥96.5%, p<0.05). Copyright © 2011 Elsevier B.V. All rights reserved.

Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004)

PubMed Central

Ruers, T.; Punt, C.; Van Coevorden, F.; Pierie, J. P. E. N.; Borel-Rinkes, I.; Ledermann, J. A.; Poston, G.; Bechstein, W.; Lentz, M. A.; Mauer, M.; Van Cutsem, E.; Lutz, M. P.; Nordlinger, B.

2012-01-01

Background This study investigates the possible benefits of radiofrequency ablation (RFA) in patients with non-resectable colorectal liver metastases. Methods This phase II study, originally started as a phase III design, randomly assigned 119 patients with non-resectable colorectal liver metastases between systemic treatment (n = 59) or systemic treatment plus RFA ( ± resection) (n = 60). Primary objective was a 30-month overall survival (OS) rate >38% for the combined treatment group. Results The primary end point was met, 30-month OS rate was 61.7% [95% confidence interval (CI) 48.2–73.9] for combined treatment. However, 30-month OS for systemic treatment was 57.6% (95% CI 44.1–70.4), higher than anticipated. Median OS was 45.3 for combined treatment and 40.5 months for systemic treatment (P = 0.22). PFS rate at 3 years for combined treatment was 27.6% compared with 10.6% for systemic treatment only (hazard ratio = 0.63, 95% CI 0.42–0.95, P = 0.025). Median progression-free survival (PFS) was 16.8 months (95% CI 11.7–22.1) and 9.9 months (95% CI 9.3–13.7), respectively. Conclusions This is the first randomized study on the efficacy of RFA. The study met the primary end point on 30-month OS; however, the results in the control arm were in the same range. RFA plus systemic treatment resulted in significant longer PFS. At present, the ultimate effect of RFA on OS remains uncertain. PMID:22431703

[The effect of laryngoscopic surgery combined with nasal endoscopic system for the treatment of vocal cords benign lesions].

PubMed

Wang, Weian; Lu, Rong

2013-06-01

To investigate the effect of laryngoscopic surgery combined with nasal endoscopic system for the treatment of vocal cords benign lesions. Fifty-two patients admitted to our department with vocal cords benign lesions (including vocal polyps, vocal nodules, vocal cord cyst) underwent laryngoscopic surgery combined with nasal endoscopic system. All patients were treated successfully once and for all without any significant postoperative complication. The laryngoscopic surgery combined with nasal endoscopic system is a safe, minimally invasive and simple method for the treatment of benign lesions of vocal cords.

Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells.

PubMed

Maniwa, Yasuhisa; Kasukabe, Takashi; Kumakura, Shunichi

2015-08-01

Although all-trans retinoic acid (ATRA) is a standard and effective drug used for differentiation therapy in acute promyelocytic leukemia, ATRA-resistant leukemia cells ultimately emerge during this treatment. Therefore, the development of new drugs or effective combination therapy is urgently needed. We demonstrate that the combined treatment of vitamin K2 and cotylenin A synergistically induced monocytic differentiation in HL-60 cells. This combined treatment also synergistically induced NBT-reducing activity and non-specific esterase-positive cells as well as morphological changes to monocyte/macrophage-like cells. Vitamin K2 and cotylenin A cooperatively inhibited the proliferation of HL-60 cells in short-term and long-term cultures. This treatment also induced growth arrest at the G1 phase. Although 5 µg/ml cotylenin A or 5 µM vitamin K2 alone reduced c-MYC gene expression in HL-60 cells to approximately 45% or 80% that of control cells, respectively, the combined treatment almost completely suppressed c-MYC gene expression. We also demonstrated that the combined treatment of vitamin K2 and cotylenin A synergistically induced the expression of cyclin G2, which had a positive effect on the promotion and maintenance of cell cycle arrest. These results suggest that the combination of vitamin K2 and cotylenin A has therapeutic value in the treatment of acute myeloid leukemia.

Mature landfill leachate treatment by coagulation/flocculation combined with Fenton and solar photo-Fenton processes.

PubMed

Amor, Carlos; De Torres-Socías, Estefanía; Peres, José A; Maldonado, Manuel I; Oller, Isabel; Malato, Sixto; Lucas, Marco S

2015-04-09

This work reports the treatment of a mature landfill leachate through the application of chemical-based treatment processes in order to achieve the discharge legal limits into natural water courses. Firstly, the effect of coagulation/flocculation with different chemicals was studied, evaluating the role of different initial pH and chemicals concentration. Afterwards, the efficiency of two different advanced oxidation processes for leachate remediation was assessed. Fenton and solar photo-Fenton processes were applied alone and in combination with a coagulation/flocculation pre-treatment. This physicochemical conditioning step, with 2 g L(-1) of FeCl3 · 6H2O at pH 5, allowed removing 63% of COD, 80% of turbidity and 74% of total polyphenols. Combining the coagulation/flocculation pre-treatment with Fenton reagent, it was possible to reach 89% of COD removal in 96 h. Moreover, coagulation/flocculation combined with solar photo-Fenton revealed higher DOC (75%) reductions than single solar photo-Fenton (54%). In the combined treatment (coagulation/flocculation and solar photo-Fenton), it was reached a DOC reduction of 50% after the chemical oxidation, with 110 kJ L(-1) of accumulated UV energy and a H2O2 consumption of 116 mM. Toxicity and biodegradability assays were performed to evaluate possible variations along the oxidation processes. After the combined treatment, the leachate under study presented non-toxicity but biodegradability increased. Copyright © 2014 Elsevier B.V. All rights reserved.

Comparison of a long-pulse Nd:YAG laser and a combined 585/1,064-nm laser for the treatment of acne scars: a randomized split-face clinical study.

PubMed

Min, Seong U K; Choi, Yu Sung; Lee, Dong Hun; Yoon, Mi Young; Suh, Dae Hun

2009-11-01

Nonablative laser is gaining popularity because of the low risk of complications, especially in patients with darker skin. To compare the efficacy and safety of a long-pulse neodymium-doped yttrium aluminium garnet (Nd:YAG) laser and a combined 585/1,064-nm laser for the treatment of acne scars. Nineteen patients with mild to moderate atrophic acne scars received four long-pulse Nd:YAG laser or combined 585/1,064-nm laser treatment sessions at fortnightly intervals. Treatments were administered randomly in a split-face manner. Acne scars showed mild to moderate improvement, with significant Echelle d'évaluation clinique des cicatrices d'acné (ECCA) score reductions, after both treatments. Although intermodality differences were not significant, combined 585/1,064-nm laser was more effective for deep boxcar scars. In patients with combined 585/1,064-nm laser-treated sides that improved more than long-pulse Nd:YAG laser-treated sides, ECCA scores were significantly lower for combined 585/1,064-nm laser treatment. Histologic evaluations revealed significantly greater collagen deposition, although there was no significant difference between the two modalities. Patient satisfaction scores concurred with physicians' evaluations. Both lasers ameliorated acne scarring with minimal downtime. In light of this finding, optimal outcomes might be achieved when laser treatment types are chosen after considering individual scar type and response.

Is there a decline in cognitive functions after combined electroconvulsive therapy and antipsychotic therapy in treatment-refractory schizophrenia?

PubMed

Pawełczyk, Agnieszka; Kołodziej-Kowalska, Emilia; Pawełczyk, Tomasz; Rabe-Jabłońska, Jolanta

2015-03-01

An analysis of literature shows that there is still little evidence concerning the efficacy of electroconvulsive therapy (ECT) combined with antipsychotic therapy in a group of treatment-resistant schizophrenia patients. More precisely, its influence on cognitive functions is still equivocal. The aim of this study was to assess the influence of ECT combined with antipsychotic therapy on working memory, attention, and executive functions in a group of treatment-refractory schizophrenia patients. Twenty-seven patients completed the study: 14 men and 13 women, aged 21 to 55 years (mean age, 32.8 years), diagnosed with treatment-resistant schizophrenia. Each patient underwent a course of ECT sessions and was treated with antipsychotic medications. Before the ECT and within 3 days after the last ECT session, the participants were assessed with the following neuropsychological tests: Trail Making Test (TMT) and Wisconsin Cart Sorting Test (WCST). There were no significant differences in the TMT and WCST results after combined ECT and antipsychotic therapy in treatment-refractory schizophrenia patients. According to the results of the neuropsychological tests, there was no decline in attention, executive functions, or working memory. The current study shows no significant difference in attention, working memory, or executive functions after treatment with a combination of electroconvulsive and antipsychotic therapy. This suggests that combined electroconvulsive therapy may not have a negative influence on the neuropsychological functioning of patients with treatment resistant schizophrenia.

40 CFR 141.718 - Treatment performance toolbox components.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... (a) Combined filter performance. Systems using conventional filtration treatment or direct filtration... the criteria in this paragraph. Combined filter effluent (CFE) turbidity must be less than or equal to... § 141.74(a) and (c). (b) Individual filter performance. Systems using conventional filtration treatment...

40 CFR 141.718 - Treatment performance toolbox components.

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (a) Combined filter performance. Systems using conventional filtration treatment or direct filtration... the criteria in this paragraph. Combined filter effluent (CFE) turbidity must be less than or equal to... § 141.74(a) and (c). (b) Individual filter performance. Systems using conventional filtration treatment...

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

Comparison possibilities of ultrasound and its combination with laser in surgery and therapy

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Menyaev, Yulian A.; Kabisov, Ruslan K.; Alkov, Sergey V.; Nesterov, A. V.; Loshchilov, Vladimir I.; Suen, James Y.

2000-05-01

This article presents the further developments of combined laser-ultrasound medical technologies with paying attention the possibility ultrasound in surgery and therapy. The analyses of main effects at the low frequency ultrasonic treatment of biotissues including cavitation, acoustic streams, acoustic pressure, mechanical influence etc are analyzed. The main promising areas of application of low frequency ultrasound are considered including bactericidal treatment of infections wounds, spray treatment of wounds in head and neck surgery, tumor treatment etc. In particular the clinical result of using ultrasonic devices based on imposing ultrasonic oscillations in a range of 22-66 kHz on a cutting instrument with a special form, radiation intensity up to 10 W/cm2 and oscillation amplitude up to 40-60 micrometers with respect to oncology for halt bleeding from a tumor, liquidating pain, acoustic denervation are presented. Some limitation of medical application of ultrasound are discussed and perspective combination with laser for increasing efficiency of new combined technologies are found. Among them: combination photodynamic therapy and ultrasonic treatment of tumors, laser-ultrasonic treatment of infections wounds including using spray, laser-ultrasonic drug delivery. The preliminary result of experimental study of some of above-mentioned technologies are presented.

Evaluation of a combination tumor treatment using thermo-triggered liposomal drug delivery and carbon ion irradiation.

PubMed

Kokuryo, Daisuke; Aoki, Ichio; Yuba, Eiji; Kono, Kenji; Aoshima, Sadahito; Kershaw, Jeff; Saga, Tsuneo

2017-07-01

The combination of radiotherapy with chemotherapy is one of the most promising strategies for cancer treatment. Here, a novel combination strategy utilizing carbon ion irradiation as a high-linear energy transfer (LET) radiotherapy and a thermo-triggered nanodevice is proposed, and drug accumulation in the tumor and treatment effects are evaluated using magnetic resonance imaging relaxometry and immunohistology (Ki-67, n = 15). The thermo-triggered liposomal anticancer nanodevice was administered into colon-26 tumor-grafted mice, and drug accumulation and efficacy was compared for 6 groups (n = 32) that received or did not receive the radiotherapy and thermo trigger. In vivo quantitative R 1 maps visually demonstrated that the multimodal thermosensitive polymer-modified liposomes (MTPLs) can accumulate in the tumor tissue regardless of whether the region was irradiated by carbon ions or not. The tumor volume after combination treatment with carbon ion irradiation and MTPLs with thermo-triggering was significantly smaller than all the control groups at 8 days after treatment. The proposed strategy of combining high-LET irradiation and the nanodevice provides an effective approach for minimally invasive cancer treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Physician orders for life-sustaining treatment (POLST): lessons learned from analysis of the Oregon POLST Registry.

PubMed

Schmidt, Terri A; Zive, Dana; Fromme, Erik K; Cook, Jennifer N B; Tolle, Susan W

2014-04-01

Physician Orders for Life-Sustaining Treatment (POLST) has become a common means of documenting patient treatment preferences. In addition to orders either for Attempt Resuscitation or Do Not Attempt Resuscitation, for patients not in cardiopulmonary arrest, POLST provides three levels of treatment: Full Treatment, Limited Interventions, and Comfort Measures Only. Oregon has an electronic registry for POLST forms completed in the state. We used registry data to examine the different combinations of treatment orders. We analyzed data from forms signed and entered into the Oregon POLST Registry in 2012. The analysis included 31,294 POLST forms. The mean Registrant age was 76.7 years. 21,396 (68.4%) had Do Not Attempt Resuscitation (DNR) orders and 9900 (31.6%) had orders for "Attempt Resuscitation". The 6 order combinations were: Do Not Resuscitate (DNR)/Comfort Measures Only 10,769 (34.4%), DNR/Limited Interventions 9306 (29.7%), DNR/Full Treatment 1211 (3.9%), Attempt Cardiopulmonary Resuscitation (CPR)/Comfort Measures Only 11 (0.04%), Attempt CPR/Limited Interventions 2281 (7.3%), and Attempt CPR/Full Treatment 7473 (23.9%). The most common order combinations were DNR/Comfort Measures Only, DNR/Limited Interventions and Attempt Resuscitation/Full Treatment. These three makes sense to health professionals. However, other order combinations that require interpretation at the time of a crisis were completed for about 10% of Registrants. These combinations need further investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Practical Applications for Single Pill Combinations in the Cardiovascular Continuum

PubMed Central

Iellamo, Ferdinando; Werdan, Karl; Narkiewicz, Krzysztof; Rosano, Giuseppe

2017-01-01

Despite the availability of new drugs and devices, the treatment of cardiovascular disease remains suboptimal. Single-pill combination therapy offers a number of potential advantages. It can combine different classes of drugs to increase efficacy while mitigating the risks of treatment-related adverse events, reduce pill burden, lower medical cost, and improve patient adherence. Furthermore, in hypertension, single pill combinations include standard to lower doses of each drug than would be necessary to achieve goals with monotherapy, which may explain their better tolerability compared with higher dose monotherapy. Combination therapy is now established in the treatment of hypertension. In ischaemic heart disease, the concept of a preventative polypill has been studied, but its benefits have not been established conclusively. However, the combination of ivabradine and beta-blockers has proven efficacy in patients with stable angina pectoris. This combination has also demonstrated benefits in patients with chronic heart failure. PMID:28785474

Combination therapy with clindamycin and rifampicin for hidradenitis suppurativa: a series of 116 consecutive patients.

PubMed

Gener, G; Canoui-Poitrine, F; Revuz, J E; Faye, O; Poli, F; Gabison, G; Pouget, F; Viallette, C; Wolkenstein, P; Bastuji-Garin, S

2009-01-01

Antibiotics are frequently used to treat hidradenitis suppurativa (HS); however, few data on their efficacy are available. To evaluate the efficacy of a combination of systemic clindamycin (300 mg twice daily) and rifampicin (600 mg daily) in the treatment of patients with severe HS. Patients (n = 116) who received this combination were studied retrospectively. The main outcome measure was the severity of the disease, assessed by the Sartorius score, before and after 10 weeks of treatment. The Sartorius score dramatically improved at the end of treatment (median = 29, interquartile range = 14.5, vs. median = 14.5, interquartile range = 11; p < 0.001), as did other parameters of severity as well as the quality of life score. Eight patients (6.9%) stopped the treatment because of side effects. The combination of clindamycin and rifampicin is effective in the treatment of severe HS. Copyright 2009 S. Karger AG, Basel.

Effect of p27 gene combined with Pientzehuang ([characters: see text]) on tumor growth in osteosarcoma-bearing nude mice.

PubMed

Ren, Shou-song; Yuan, Fang; Liu, Ying-hong; Zhou, Le-tian; Li, Jun

2015-11-01

To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang ([characters: see text]) on the growth of xenografted human osteosarcoma in nude mice. Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot. The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was significantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was significantly increased compared with the blank control group (P<0.05); and it was significantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05). p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.

Sample size requirements for separating out the effects of combination treatments: Randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis

PubMed Central

2011-01-01

Background In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 × 2 factorial design. Methods We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two. Results In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions. Conclusions Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 × 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial. Trial registration Current Controlled Trials ISRCTN61649292 PMID:21288326

Successful retreatment with sofosbuvir plus ledipasvir for cirrhotic patients with hepatitis C virus genotype 1b, who discontinued the prior treatment with asunaprevir plus daclatasvir: A case series and review of the literature

PubMed Central

Haga, Yuki; Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Ooka, Yoshihiko; Takahashi, Koji; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Chiba, Tetsuhiro; Maruyama, Hitoshi; Yokosuka, Osamu; Takada, Nobuo; Moriyama, Mitsuhiko; Imazeki, Fumio; Kato, Naoya

2018-01-01

Background Interferon-free treatment results in higher sustained virologic response (SVR) rates, with no serious adverse events in hepatitis C virus (HCV)-infected patients. However, in some patients with treatment-failure in HCV NS5A inhibitor-including interferon-free regimens, the treatment-emergent HCV NS5A resistance-associated variants (RAVs), which are resistant to interferon-free retreatment including HCV NS5A inhibitors, are observed. In HCV-infected Japanese patients with daclatasvir and asunaprevir treatment failure, retreatment with sofosbuvir and ledipasvir could lead to only ∼70% SVR rates. Case summary Three HCV genotype (GT)-1b-infected cirrhotic patients who discontinued the combination of daclatasvir and asunaprevir due to adverse drug reactions within 4 weeks; retreatment with sofosbuvir and ledipasvir combination could result in SVR in these patients without RAVs. One HCV GT-1b-infected cirrhotic patient who discontinued the combination of daclatasvir and asunaprevir due to viral breakthrough at week 10; retreatment with sofosbuvir and ledipasvir combination for this patient with the treatment-emergent HCV NS5A RAV-Y93H resulted in viral relapse at week 4 after the end of the treatment. Conclusion Retreatment with sofosbuvir and ledipasvir is effective for HCV GT-1b patients who discontinue the combination of daclatasvir and asunaprevir within 4 weeks. The treatment response should be related to the existence of treatment-emergent HCV NS5A RAVs, but may not be related to the short duration of treatment. PMID:29435197

Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

PubMed

Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

2016-06-01

Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

A combined group treatment for nightmares and insomnia in combat veterans: a pilot study.

PubMed

Swanson, Leslie M; Favorite, Todd K; Horin, Elizabeth; Arnedt, J Todd

2009-12-01

Insomnia and nightmares are hallmarks of posttraumatic stress disorder (PTSD). Sleep disturbances in PTSD negatively impact clinical course and functioning. In this open clinical trial, the preliminary effects of a combined treatment for insomnia and nightmares in combat veterans with PTSD were assessed. Ten combat veterans participated in a 10-session group treatment combining cognitive-behavioral therapy for insomnia with exposure, rescripting, and relaxation therapy. Participants maintained daily sleep and dream diaries and completed self-report measures of sleep quality and PTSD symptoms pre- and posttreatment. Participants reported improvements in sleep and nightmares following treatment. Future research using controlled designs to evaluate this treatment is warranted.

Clindamycin phosphate-tretinoin combination gel revisited: status report on a specific formulation used for acne treatment.

PubMed

Del Rosso, James Q

2017-03-01

Topical agents, including retinoids and antibiotics, are commonly used to treat acne vulgaris (AV) and remain as components of acne treatment guidelines. Approved topical combination formulations offer the advantages of established efficacy, decreased frequency of application, and improved convenience for patients. This article discusses both clindamycin phosphate (CP) and tretinoin (Tret) as components of a topical aqueous-based combination gel that has been shown to be effective, safe, and well tolerated for treatment of facial AV. Clinically relevant considerations with use of this treatment are also discussed, including therapeutic advantages and potential limitations.

Treatment for preventing tuberculosis in children and adolescents: a randomized clinical trial of a 3-month, 12-dose regimen of a combination of rifapentine and isoniazid.

PubMed

Villarino, M Elsa; Scott, Nigel A; Weis, Stephen E; Weiner, Marc; Conde, Marcus B; Jones, Brenda; Nachman, Sharon; Oliveira, Ricardo; Moro, Ruth N; Shang, Nong; Goldberg, Stefan V; Sterling, Timothy R

2015-03-01

Three months of a once-weekly combination of rifapentine and isoniazid for treatment of latent tuberculosis infection is safe and effective for persons 12 years or older. Published data for children are limited. To compare treatment safety and assess noninferiority treatment effectiveness of combination therapy with rifapentine and isoniazid vs 9 months of isoniazid treatment for latent tuberculosis infection in children. A pediatric cohort nested within a randomized, open-label clinical trial conducted from June 11, 2001, through December 17, 2010, with follow-up through September 5, 2013, in 29 study sites in the United States, Canada, Brazil, Hong Kong (China), and Spain. Participants were children (aged 2-17 years) who were eligible for treatment of latent tuberculosis infection. Twelve once-weekly doses of the combination drugs, given with supervision by a health care professional, for 3 months vs 270 daily doses of isoniazid, without supervision by a health care professional, for 9 months. We compared rates of treatment discontinuation because of adverse events (AEs), toxicity grades 1 to 4, and deaths from any cause. The equivalence margin for the comparison of AE-related discontinuation rates was 5%. Tuberculosis disease diagnosed within 33 months of enrollment was the main end point for testing effectiveness. The noninferiority margin was 0.75%. Of 1058 children enrolled, 905 were eligible for evaluation of effectiveness. Of 471 in the combination-therapy group, 415 (88.1%) completed treatment vs 351 of 434 (80.9%) in the isoniazid-only group (P = .003). The 95% CI for the difference in rates of discontinuation attributed to an AE was -2.6 to 0.1, which was within the equivalence range. In the safety population, 3 of 539 participants (0.6%) who took the combination drugs had a grade 3 AE vs 1 of 493 (0.2%) who received isoniazid only. Neither arm had any hepatotoxicity, grade 4 AEs, or treatment-attributed death. None of the 471 in the combination-therapy group developed tuberculosis vs 3 of 434 (cumulative rate, 0.74%) in the isoniazid-only group, for a difference of -0.74% and an upper bound of the 95% CI of the difference of +0.32%, which met the noninferiority criterion. Treatment with the combination of rifapentine and isoniazid was as effective as isoniazid-only treatment for the prevention of tuberculosis in children aged 2 to 17 years. The combination-therapy group had a higher treatment completion rate than did the isoniazid-only group and was safe. clinicaltrials.gov Identifier: NCT00023452.

Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-1-0109 TITLE: Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Elizabeth A. Mittendorf, MD, PhD CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: October...CONTRACT NUMBER Combination Immunotherapy for the Treatment of High-Risk HER2-Positive Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0109 5c. PROGRAM

Combined treatment with ABT-737 and VX-680 induces apoptosis in Bcl-2- and c-FLIP-overexpressing breast carcinoma cells.

PubMed

Choi, Jung Eun; Woo, Seon Min; Min, Kyoung-Jin; Kang, Su Hwan; Lee, Soo Jung; Kwon, Taeg Kyu

2015-03-01

ABT-737, a BH3-mimetic small-molecule inhibitor, binds with very high affinity to Bcl-2, Bcl-xL and Bcl-w, and inhibits their activity. Aurora kinase is one of the serine/threonine kinase family members and is a vital and critical regulator of mitosis and meiosis. In the present study, we investigated the effects and mechanisms of a combined treatment of ABT-737 and VX-680 (Aurora kinase inhibitor) in human breast cancer MDA-MB‑435S cells. ABT-737 plus VX-680 induced caspase-dependent apoptosis in the human breast cancer cells. Combined treatment with ABT-737 and VX-680 led to the downregulation of Bcl-2 expression at the transcriptional level and the downregulation of c-FLIP and Mcl-1 expression at the post-transcriptional level. Overexpression of Bcl-2 or c-FLIP could not block the induction of apoptosis caused by the combined treatment with ABT-737 and VX-680. However, overexpression of Mcl-1 partially inhibited the induction of apoptosis. In contrast, the combined treatment with ABT-737 and VX680 had no effect on the apoptosis in normal cells. Taken together, our study demonstrated that combined treatment with ABT-737 and VX-680 induced apoptosis in anti‑apoptotic protein (Bcl-2 or c-FLIP)-overexpressing cells.

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.

[Combined physiotherapy of chronic infectious prostatitis].

PubMed

Churakov, A A; Popkov, V M; Zemskov, S P; Glybochko, P V; Bliumberg, B I

2007-01-01

Our experience with therapy of 259 outpatients with chronic infectious prostatitis (CIP) aged 16-55 years has demonstrated that combined treatment of CIP with rectal digital massage of the prostate, electrophoresis of chimotripsin solution with dimexide and local magnetotherapy (Intramag unit) significantly raises treatment efficacy, shortens treatment, prevents complications.

Vascular Disruption in Combination with mTOR Inhibition in Renal Cell Carcinoma

PubMed Central

Ellis, Leigh; Shah, Preeti; Hammers, Hans; Lehet, Kristin; Sotomayor, Paula; Azabdaftari, Gissou; Seshadri, Mukund; Pili, Roberto

2013-01-01

Renal cell carcinoma (RCC) is an angiogenesis-dependent and hypoxia-driven malignancy. As a result, there has been an increased interest in the use of antiangiogenic agents for the management of RCC in patients. However, the activity of tumor-vascular disrupting agents (tumor-VDA) has not been extensively examined against RCC. In this study, we investigated the therapeutic efficacy of the tumor-VDA ASA404 (DMXAA, 5,6-dimethylxanthenone-4-acetic acid, or vadimezan) in combination with the mTOR inhibitor everolimus (RAD001) against RCC. In vitro studies were carried out using human umbilical vein endothelial cells and in vivo studies using orthotopic RENCA tumors and immunohistochemical patient tumor-derived RCC xenografts. MRI was used to characterize the vascular response of orthotopic RENCA xenografts to combination treatment. Therapeutic efficacy was determined by tumor growth measurements and histopathologic evaluation. ASA404/everolimus combination resulted in enhanced inhibition of endothelial cell sprouting in the 3-dimensional spheroid assay. MRI of orthotopic RENCA xenografts revealed an early increase in permeability 4 hours posttreatment with ASA404, but not with everolimus. Twenty-four hours after treatment, a significant reduction in blood volume was observed with combination treatment. Correlative CD31/NG2 staining of tumor sections confirmed marked vascular damage following combination therapy. Histologic sections showed extensive necrosis and a reduction in the viable rim following combination treatment compared with VDA treatment alone. These results show the potential of combining tumor-VDAs with mTOR inhibitors in RCC. Further investigation into this novel combination strategy is warranted. PMID:22084164

Cost-effectiveness comparison of lamivudine plus adefovir combination treatment and nucleos(t)ide analog monotherapies in Chinese chronic hepatitis B patients.

PubMed

Zhang, Chi; Ke, Weixia; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

2016-01-01

Lamivudine (LAM) plus adefovir (ADV) combination therapy is clinically efficacious for treating chronic hepatitis B (CHB) patients in China, but no pharmacoeconomic evaluations of this strategy are available. The aim of this study was to examine the cost-effectiveness of LAM plus ADV combination treatment compared with five other nucleos(t)ide analog monotherapies (LAM, ADV, telbivudine [TBV], entecavir [ETV], and tenofovir [TDF]). To simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for different therapy options, a Markov model that included five initial monotherapies and LAM plus ADV combination as an initial treatment was developed. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: direct use of ETV + ADV) were considered separately for treating patients refractory to initial therapy. One-way and probabilistic sensitivity analyses were used to explore model uncertainties. In base-case analysis, ETV had the lowest lifetime cost and served as the reference therapy. Compared to the reference, LAM, ADV, and TBV had higher costs and lower efficacy, and were completely dominated by ETV. LAM plus ADV combination therapy or TDF was more efficacious than ETV, but also more expensive. Although the incremental cost-effectiveness ratios of combination therapy or TDF were both higher than the willingness-to-pay threshold of $20,466/QALY gained for the reference treatment, in an alternative scenario analysis LAM plus ADV combination therapy would be the preferable treatment option. ETV and LAM plus ADV combination therapy are both cost-effective strategies for treating Chinese CHB patients.

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.

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

PubMed

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

1998-06-01

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

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta-Analysis of Randomized Trials.

PubMed

Graudal, Niels; Hubeck-Graudal, Thorbjørn; Faurschou, Mikkel; Baslund, Bo; Jürgens, Gesche

2015-11-01

The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (-0.09 units [-0.61, 0.44]) of treatment or during the first 2 years (0.66 units [-0.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors. © 2015, American College of Rheumatology.

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

PubMed

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

2017-05-01

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

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

PubMed Central

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

2018-01-01

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

Attention and interpretation bias modification treatment for social anxiety disorder: A randomized clinical trial of efficacy and synergy.

PubMed

Naim, Reut; Kivity, Yogev; Bar-Haim, Yair; Huppert, Jonathan D

2018-06-01

Attention bias modification treatment (ABMT) and cognitive bias modification of interpretation (CBM-I) both have demonstrated efficacy in alleviating social anxiety, but how they compare with each other, their combination, and with a combined control condition has not been studied. We examined their relative and combined efficacy compared to control conditions in a randomized controlled trial (RCT). Ninety-five adults diagnosed with social anxiety disorder (SAD), were randomly allocated to 4 groups: ABMT + CBM-I control (hereafter ABMT; n = 23), CBM-I + ABMT control (hereafter CBM-I; n = 24), combined ABMT + CBM-I (n = 23), and combined control (n = 25). Treatment included eight sessions over four weeks. Clinician-rated and self-reported measures of social anxiety symptoms, functional impairment, and threat-related attention and interpretive biases were evaluated at baseline, post-treatment, and 3-month follow-up. ABMT yielded greater symptom reduction as measured by both clinician-ratings (Cohen's ds = 0.57-0.70) and self-reports (ds = 0.70-0.85) compared with the CBM-I, the combined ABMT + CBM-I, and the combined control conditions. Neither of the other conditions demonstrated superior symptom change compared to the control condition. No group differences were found for functioning or cognitive biases measures. Limitations mainly include the mix of active and control treatments applied across the different groups. Therefore, the net effect of each of the treatments by itself could not be clearly tested. Results suggest superiority of ABMT compared to CBM-I and their combination in terms of symptom reduction. Possible interpretations and methodological issues underlying the observed findings are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-04-01

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

Behavioral responses and fluid regulation in male rats after combined dietary sodium deficiency and water deprivation.

PubMed

Lucia, Kimberly J; Curtis, Kathleen S

2018-02-01

Most investigators use a single treatment such as water deprivation or dietary sodium deficiency to evaluate thirst or sodium appetite, which underlie behavioral responses to body fluid challenges. The goal of the present experiments was to assess the effects of combined treatments in driving behaviors. Therefore, we evaluated the effect of combined overnight water deprivation and dietary sodium deficiency on water intake and salt intake by adult male rats in 2-bottle (0.5M NaCl and water) tests. Overnight water deprivation alone increased water intake, and 10days of dietary sodium deficiency increased 0.5M NaCl intake, with a secondary increase in water intake. During combined water deprivation and dietary sodium deficiency, water intake was enhanced and 0.5M NaCl was reduced, but not eliminated, suggesting that physiologically relevant behavioral responses persist. Nonetheless, the pattern of fluid intake was altered by the combined treatments. We also assessed the effect of these behaviors on induced deficits in body sodium and fluid volume during combined treatments and found that, regardless of treatment, fluid ingestion partially repleted the induced deficits. Finally, we examined urine volume and sodium excretion during dietary sodium deficiency with or without overnight water deprivation and found that, whether or not rats were water deprived, and regardless of water consumption, sodium excretion was minimal. Thus, the combination of water deprivation and dietary sodium deficiency appears to arouse drives that stimulate compensatory behavioral responses. These behaviors, in conjunction with physiological adaptations to the treatments, underlie body sodium and volume repletion in the face of combined water deprivation and dietary sodium deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Combined application of autologous serum eye drops and silicone hydrogel lenses for the treatment of persistent epithelial defects.

PubMed

Choi, Jin A; Chung, So-Hyang

2011-11-01

We investigated the utility of a combination of autologous serum eye drops and a silicone-hydrogel (SH) lens in the treatment of persistent epithelial defects (PEDs). Eight patients who had distinct PED conditions were treated with 50% (v/v) autologous serum eye drops in combination with silicone hydrogel contact lenses and prospectively observed. The pathogenesis of PEDs included Sjogren-type dry eye syndrome, graft-versus-host disease, toxic keratitis, limbal cell deficiency, superior limbic keratoconjunctivitis, and neurotrophic keratitis. The patients had PEDs for 90±81.76 days (range: 30-240 days). Before the initiation of the combined treatment, three patients had already been unsuccessfully treated with SH lenses, and five patients had received serum eye drops alone. The PEDs of the eight eyes healed after a treatment period of 11.8±4.9 days. No visible deposits were noted on the surface of any contact lens. These findings demonstrate that the combination of an SH lens and serum eye drops may be effective in the treatment of intractable PEDs.

[Clinical observation on idiopathic tinnitus treated with acupuncture, buzhong yiqi tang and cizhu wan].

PubMed

Chen, Surong; Tan, Xuming; Fei, Lanbo; Xiang, Xiande

2018-04-12

To observe the differences in the clinical therapeutic effects on idiopathic tinnitus between the combined therapy with acupuncture and the modified formula of buzhong yiqi tang and cizhu wan and the simple administration of the modified formula of buzhong yiqi tang and cizhu wan . A total of 60 patients were randomized into a combined treatment group and an herbal medicine group, 30 cases in each one and 2 cases dropped out in the herbal medicine group. In the combined treatment group, acupuncture was given at the local acupoints for tinnitus, such as Yifeng (TE 17), penetrating needling technique from Ermen (TE 21) to Tinggong (SI 19) and Tinghui (GB 2) combined with the scalp acupuncture [the vertigo-auditory area, Baihui (GV 20)] and the oral administration of the modified formula of buzhong yiqi tang and cizhu wan . In the herbal medicine group, the oral administration of the modified formula of buzhong yiqi tang and cizhu wan was only applied. The treatment was given once a day in each group, 5 times a week for acupuncture and 7 times a week for the oral administration of herbal medicine. Totally, the treatment for 6 weeks was required in the two groups. Before and after treatment, the tinnitus severity score (TSS) and the score of tinnitus handicap inventory (THI) were observed and the clinical therapeutic effects were compared between the two groups. After treatment, the TSS and THI scores reduced as compared with those before treatment in the two groups (all P <0.05). The scores in the combined treatment group were lower than those in the herbal medicine group (both P <0.05). The total effective rate in the combined treatment group was 93.3% (28/30), better than 67.9% (19/28) in the herbal medicine group ( P <0.05). The combined treatment with scalp acupuncture, acupuncture around the ear and the modified formula of buzhong yiqi tang and cizhu wan achieve the superior therapeutic effects on idiopathic tinnitus as compared with the simple oral administration of the modified formula of buzhong yiqi tang and cizhu wan .

Gastrointestinal Toxicities With Combined Antiangiogenic and Stereotactic Body Radiation Therapy

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

Pollom, Erqi L.; Deng, Lei; Pai, Reetesh K.

2015-07-01

Combining the latest targeted biologic agents with the most advanced radiation technologies has been an exciting development in the treatment of cancer patients. Stereotactic body radiation therapy (SBRT) is an ablative radiation approach that has become established for the treatment of a variety of malignancies, and it has been increasingly used in combination with biologic agents, including those targeting angiogenesis-specific pathways. Multiple reports have emerged describing unanticipated toxicities arising from the combination of SBRT and angiogenesis-targeting agents, particularly of late luminal gastrointestinal toxicities. In this review, we summarize the literature describing these toxicities, explore the biological mechanism of action ofmore » toxicity with the combined use of antiangiogenic therapies, and discuss areas of future research, so that this combination of treatment modalities can continue to be used in broader clinical contexts.« less

Regulation Mechanism of Novel Thermomechanical Treatment on Microstructure and Properties in Al-Zn-Mg-Cu Alloy

NASA Astrophysics Data System (ADS)

Chen, Zhiguo; Ren, Jieke; Zhang, Jishuai; Chen, Jiqiang; Fang, Liang

2016-02-01

Scanning electron microscopy, transmission electron microscopy, tensile test, exfoliation corrosion test, and slow strain rate tensile test were applied to investigate the properties and microstructure of Al-Zn-Mg-Cu alloy processed by final thermomechanical treatment, retrogression reaging, and novel thermomechanical treatment (a combination of retrogression reaging with cold or warm rolling). The results indicate that in comparison with conventional heat treatment, the novel thermomechanical treatment reduces the stress corrosion susceptibility. A good combination of mechanical properties, stress corrosion resistance, and exfoliation corrosion resistance can be obtained by combining retrogression reaging with warm rolling. The mechanism of the novel thermomechanical treatment is the synergistic effect of composite microstructure such as grain morphology, dislocation substructures, as well as the morphology and distribution of primary phases and precipitations.

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

PubMed

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

2017-02-01

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

96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B.

PubMed

Hui, Chee-Kin; Zhang, Hai-Ying; Bowden, Scott; Locarnini, Stephen; Luk, John M; Leung, Kar-Wai; Yueng, Yui-Hung; Wong, April; Rousseau, Frank; Yuen, Kwok-Yung; Naoumov, Nikolai N; Lau, George K K

2008-05-01

In order to prevent the occurrence of drug-resistant mutants associated with treatment for chronic hepatitis B virus (HBV) infection, combination therapy is being developed. To determine the efficacy of adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy in chronic HBV infection. Thirty treatment-nai ve, HBeAg-positive patients were randomized to combination ADV plus FTC (n=14) or ADV plus placebo monotherapy (n=16) for 96 weeks. HBV DNA was measured by polymerase chain reaction. Treatment was stopped in those with HBeAg seroconversion. The median decrease in HBV DNA at week 96 was higher in the combination group (-5.30 vs. -3.98 log(10)copies/ml, p=0.05). More patients in the combination group had normalization of alanine aminotransaminase and HBV DNA<300 copies/ml at week 96 when compared with the monotherapy group [11 of the 14 patients (78.6%) vs. 6 of the 16 patients (37.5%), p=0.03]. However, HBeAg seroconversion at week 96 was similar in the 2 groups [2/14 (14.3%) vs. 4/16 (25.0%), p=NS]. No ADV or FTC resistance was detected at week 96. In those with HBeAg seroconversion, 50.0% had post-treatment relapse. Combination ADV plus FTC resulted in more potent suppression of HBV DNA over 96 weeks of therapy.

Mechanism of Chemoprevention against Colon Cancer Cells Using Combined Gelam Honey and Ginger Extract via mTOR and Wnt/β-catenin Pathways.

PubMed

Wee, Lee Heng; Morad, Noor Azian; Aan, Goon Jo; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2015-01-01

The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.

[Comparative study of combined local treatment (sulfadimidine, metronidazole and nystatin) and the standard monotherapy in uncomplicated bacterial vaginosis].

PubMed

Milánkovits, Márton; Baksay, László; Plachy, János

2002-12-22

Comparative, in vivo, human, prospective, single blind, clinical and microbiological diagnoses based and randomised study of the treatment of uncomplicated bacterial vaginosis with two forms of combined (metronidazole + nystatin + sulfadimidin) vaginal suppositories (laminated and mixed containing the same ingredients) and the standard preparations available in the Hungarian market (Dalacin vaginal cream and Klion vaginal suppository). The examinations involved 60 volunteers and were performed in the Gynecological Outpatient Clinic of the Council of Erd, the microbiological samples were examined at Saint Rókus Hospital in Budapest. The combined treatment was better tolerated and resulted in normal vaginal pH significantly more often at the same rate of recovery. The combined treatment is simultaneously effective in cases of the most prevalent coinfections too.

Combined treatment with cotylenin A and phenethyl isothiocyanate induces strong antitumor activity mainly through the induction of ferroptotic cell death in human pancreatic cancer cells.

PubMed

Kasukabe, Takashi; Honma, Yoshio; Okabe-Kado, Junko; Higuchi, Yusuke; Kato, Nobuo; Kumakura, Shunichi

2016-08-01

The treatment of pancreatic cancer, one of the most aggressive gastrointestinal tract malignancies, with current chemotherapeutic drugs has had limited success due to its chemoresistance and poor prognosis. Therefore, the development of new drugs or effective combination therapies is urgently needed. Cotylenin A (CN-A) (a plant growth regulator) is a potent inducer of differentiation in myeloid leukemia cells and exhibits potent antitumor activities in several cancer cell lines. In the present study, we demonstrated that CN-A and phenethyl isothiocyanate (PEITC), an inducer of reactive oxygen species (ROS) and a dietary anticarcinogenic compound, synergistically inhibited the proliferation of MIAPaCa-2, PANC-1 and gemcitabine-resistant PANC-1 cells. A combined treatment with CN-A and PEITC also effectively inhibited the anchorage-independent growth of these cancer cells. The combined treatment with CN-A and PEITC strongly induced cell death within 1 day at concentrations at which CN-A or PEITC alone did not affect cell viability. A combined treatment with synthetic CN-A derivatives (ISIR-005 and ISIR-042) or fusicoccin J (CN-A-related natural product) and PEITC did not have synergistic effects on cell death. The combined treatment with CN-A and PEITC synergistically induced the generation of ROS. Antioxidants (N-acetylcysteine and trolox), ferroptosis inhibitors (ferrostatin-1 and liproxstatin), and the lysosomal iron chelator deferoxamine canceled the synergistic cell death. Apoptosis inhibitors (Z-VAD-FMK and Q-VD-OPH) and the necrosis inhibitor necrostatin-1s did not inhibit synergistic cell death. Autophagy inhibitors (3-metyladenine and chloroquine) partially prevented cell death. These results show that synergistic cell death induced by the combined treatment with CN-A and PEITC is mainly due to the induction of ferroptosis. Therefore, the combination of CN-A and PEITC has potential as a novel therapeutic strategy against pancreatic cancer.

Fungicide seed treatments for evaluating the corn seedling disease complex following a winter rye cover crop

USDA-ARS?s Scientific Manuscript database

Seed treatments have been used to manage corn seedling diseases since the 1970’s and they contain a combination of active ingredients with specificity towards different pathogens. We hypothesized that using different seed treatment combinations and assessing seedling disease incidence and severity ...

Adherence to Pharmacological Treatment for Juvenile Bipolar Disorder

ERIC Educational Resources Information Center

Drotar, Dennis; Greenley, Rachel Neff; Demeter, Christine A.; McNamara, Nora K.; Stansbrey, Robert J.; Calabrese, Joseph R.; Stange, Jonathan; Vijay, Priya; Findling, Robert L.

2007-01-01

Objective: The objective of this study was to describe the prevalence and correlates of adherence to divalproex sodium (DVPX) and lithium carbonate (Li) combination treatment during the initial stabilization treatment phase. Method: Adherence to Li/DVPX combination therapy was measured by the presence or absence of minimum serum concentrations of…

[Impact on serum 5-HT and TH1/TH2 in patients of depressive disorder at acute stage treated with acupuncture and western medication].

PubMed

Liu, Yi; Feng, Hui; Mao, Hongjing; Mo, Yali; Yin, Yan; Liu, Wenjuan; Song, Mingfen; Wang, Shengdong

2015-06-01

To compare the difference in depression relief in the treatment of depressive disorder at the acute stage between the combined therapy of acupuncture and 5-HT (5-hydroxytryptamine) selective serotonini reuptake inhibitors (SSRIs) and the single application of SSRIs and explore the impact on the imbalance of 5-HT and TH1/TH2. Ninety cases of depressive disorder at the acute stage were randomized into a combined therapy group and a medication group, 45 cases in each one. In the medication group, SSRIs were prescribed forl oral administration, once or twice a day, continuously for 4 weeks. In the combined therapy group, on the basis of treatment as the medication group, acupuncture was combined. The main acupoints were Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), Fengchi (GB 20), Dazhui (GV 14) and Sishencong (EX-HN 1), once every two. days, continuously for 4 weeks. Before treatment, and after the 1st, 2nd and 4th weeks of treatment, the Hamilton depression scale (HAMD) was used to evaluate the depression severity. Separately, before and after the 4 weeks of treatment, the levels of serum 5-HT, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-10 (IL-10) were determined and compared with those in 45 cases of the healthy group. HAMD score was reduced in the 1st, 2nd and 4th weeks of treatment as compared with that before treatment in the combined therapy group (all P<0 01). HAMD score was reduced in the 2nd and 4th weeks of treatment as compared with that before treatment in the medication group (all P<0. 01). HAMD scores in the combined therapy group were lower than those in the medication group in the 1st, 2nd and 4th weeks of treatment (all P< 0. 01). Before treatment, in the combined therapy group and the medication group, the levels of serum 5-HT, IL-4 and IL-10 were all lower than those in the healthy group (all P<0. 01); the levels of IL-1β and IL-6 were higher than those in the healthy group (all P<0. 01). In the combined therapy group and the medication group, the levels of 5-HT, IL-4 and IL-10 in 4 weeks of treatment were all increased as compared with those before treatment (all P<0. 01), and the levels of IL-1β and IL-6 were lower than those before treatment (all P<0. 01). In the combined therapy group, the levels of IL-1β and IL-6 in 4 weeks of treatment were lower than those in the medication group, and the levels of 5-HT, IL-4 and IL-10 were higher than those in the medication group (P<0. 01, P< 0. 05). The combined therapy of acupuncture and SSRIs achieves much quicker and more effective re-' sult for relieving depression in the patients of depressive disorder as compared with simple oral administration of' SSRIs, and much more contributes to adjust the imbalance of serum 5-HT and TH1/TH2.

A retrospective study of treatment persistence and adherence to α-blocker plus antimuscarinic combination therapies, in men with LUTS/BPH in the Netherlands.

PubMed

Drake, Marcus J; Bowditch, Sally; Arbe, Emilio; Hakimi, Zalmai; Guelfucci, Florent; Amri, Ikbel; Nazir, Jameel

2017-05-22

To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47-164 days; adjusted HR range, 1.27-1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in the Netherlands showed that treatment persistence was significantly greater in those who received a FDC tablet compared with combination therapy given concomitantly. The study also shows that treatment persistence was extended in men who received combination therapy containing solifenacin compared with other antimuscarinics. Overall, these findings may be useful for prescribers, as improved persistence on-treatment may translate into improved outcomes for men with LUTS/BPH. Further study is warranted to establish the key drivers of persistence in men receiving combination therapy for LUTS/BPH.

Low-fluence Q-switched Nd: YAG 1064-nm laser and intense pulsed light for the treatment of melasma.

PubMed

Vachiramon, V; Sirithanabadeekul, P; Sahawatwong, S

2015-07-01

Low-fluence Q-switched Nd:YAG 1064 nm laser (LFQS) and intense pulsed light (IPL) have been shown to be effective in the treatment of melasma. LFQS can target deeper pigment, while IPL can target a wide range of cutaneous structures. However, there is limited information on efficacy and side-effects of the combined treatment. To compare the efficacy and safety of combined LFQS and IPL therapy with LFQS monotherapy in the treatment of melasma. Twenty female patients with mixed-type melasma on both cheeks were treated with LFQS on full face for five sessions at 1-week intervals. One side of the face was randomly assigned to receive additional three sessions of IPL treatments at 2-week intervals. Patients were evaluated 12 weeks after the last treatment. Outcome measures include the assessment by colorimeter and calculated as relative lightness index (R*LI), modified Melasma Area and Severity Index (mMASI), patient satisfaction and adverse effects. Eighteen patients completed the study. Both sides of the face showed significant improvement of R*LI and mMASI. A more rapid improvement of R*LI and mMASI was observed on combined side. At the end of treatment, 55% improvement and 37% improvement of R*LI was observed on combined side and monotherapy side respectively. The overall patients' satisfaction was in favour of the combined side. Recurrence occurred on both sides but there was still a significant decrease compared to baseline. No serious side effect was noted. The combination of LFQS and IPL results in faster clearance of melasma and is more effective than LFQS alone for melasma treatment. However, recurrence is still inevitable. © 2014 European Academy of Dermatology and Venereology.

Combined Treatment With Peroxisome Proliferator-Activated Receptor (PPAR) Gamma Ligands and Gamma Radiation Induces Apoptosis by PPARγ-Independent Up-Regulation of Reactive Oxygen Species-Induced Deoxyribonucleic Acid Damage Signals in Non-Small Cell Lung Cancer Cells

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

Han, Eun Jong; Im, Chang-Nim; Park, Seon Hwa

2013-04-01

Purpose: To investigate possible radiosensitizing activities of the well-known peroxisome proliferator-activated receptor (PPAR)γ ligand ciglitazone and novel PPARγ ligands CAY10415 and CAY10506 in non-small cell lung cancer (NSCLC) cells. Methods and Materials: Radiosensitivity was assessed using a clonogenic cell survival assay. To investigate the mechanism underlying PPARγ ligand-induced radiosensitization, the subdiploid cellular DNA fraction was analyzed by flow cytometry. Activation of the caspase pathway by combined PPARγ ligands and γ-radiation treatment was detected by immunoblot analysis. Reactive oxygen species (ROS) were measured using 2,7-dichlorodihydrofluorescein diacetate and flow cytometry. Results: The 3 PPARγ ligands induced cell death and ROS generation inmore » a PPARγ-independent manner, enhanced γ-radiation–induced apoptosis and caspase-3–mediated poly (ADP-ribose) polymerase (PARP) cleavage in vitro. The combined PPARγ ligand/γ-radiation treatment triggered caspase-8 activation, and this initiator caspase played an important role in the combination-induced apoptosis. Peroxisome proliferator-activated receptor-γ ligands may enhance the γ-radiation-induced DNA damage response, possibly by increasing γ-H2AX expression. Moreover, the combination treatment significantly increased ROS generation, and the ROS scavenger N-acetylcysteine inhibited the combined treatment-induced ROS generation and apoptotic cell death. Conclusions: Taken together, these results indicated that the combined treatment of PPARγ ligands and γ-radiation synergistically induced DNA damage and apoptosis, which was regulated by ROS.« less

Novel therapeutic strategy targeting the Hedgehog signalling and mTOR pathways in biliary tract cancer

PubMed Central

Zuo, M; Rashid, A; Churi, C; Vauthey, J-N; Chang, P; Li, Y; Hung, M-C; Li, D; Javle, M

2015-01-01

Background: Activation of the PI3K/mTOR and Hedgehog (Hh) signalling pathways occurs frequently in biliary tract cancer (BTC). Crosstalk between these pathways occurs in other gastrointestinal cancers. The respective signalling inhibitors rapamycin and vismodegib may inhibit BTC synergistically and suppress cancer stem cells (CSCs). Methods: Gene expression profiling for p70S6k and Gli1 was performed with BTC cell lines. Tumour and pathway inhibitory effects of rapamycin and vismodegib were investigated in BTC preclinical models and CSCs. Results: Rapamycin and vismodegib synergistically reduced BTC cell viability and proliferation. This drug combination arrested BTC Mz-ChA-1 cells in the G1 phase but had no significant effect on the cell cycle of BTC Sk-ChA-1 cells. Combined treatment inhibited the proliferation of CSCs and ALDH-positive cells. Nanog and Oct-4 expression in CSCs was decreased by the combination treatment. Western blotting results showed the p-p70S6K, p-Gli1, p-mTOR, and p-AKT protein expression were inhibited by the combination treatment in BTC cells. In an Mz-ChA-1 xenograft model, combination treatment resulted in 80% inhibition of tumour growth and prolonged tumour doubling time. In 4 of 10 human BTC specimens, tumour p-p70S6K and Gli1 protein expression levels were decreased with the combination treatment. Conclusions: Targeted inhibition of the PI3K/mTOR and Hhpathways indicates a new avenue for BTC treatment with combination therapy. PMID:25742482

Valproic Acid Induces Endocytosis-Mediated Doxorubicin Internalization and Shows Synergistic Cytotoxic Effects in Hepatocellular Carcinoma Cells

PubMed Central

Saha, Subbroto Kumar; Yin, Yingfu; Kim, Kyeongseok; Yang, Gwang-Mo; Abdal Dayem, Ahmed; Choi, Hye Yeon; Cho, Ssang-Goo

2017-01-01

Valproic acid (VPA), a well-known histone deacetylase (HDAC) inhibitor, is used as an anti-cancer drug for various cancers, but the synergistic anti-cancer effect of VPA and doxorubicin (DOX) combination treatment and its potential underlying mechanism in hepatocellular carcinoma (HCC) remain to be elucidated. Here, we evaluate the mono- and combination-therapy effects of VPA and DOX in HCC and identify a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and Western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC. PMID:28498322

Fixed-combination treatments for intraocular hypertension in Chinese patients – focus on bimatoprost-timolol

PubMed Central

Fang, Yuan; Ling, Zhihong; Sun, Xinghuai

2015-01-01

Glaucoma is a common eye disease that can lead to irreversible vision loss if left untreated. The early diagnosis and treatment of primary open-angle glaucoma is challenging, and visual impairment in Chinese glaucoma patients is a serious concern. Most of these patients need more than one topical antiglaucoma agent to control their intraocular pressures (IOPs). In the People’s Republic of China, the daily cost of different glaucoma medication varies greatly, and the treatment habits differ throughout the country. Prostaglandin analogs (PGAs) are recommended as first-line monotherapy, because of their efficacy and low risk of systemic side effects. Fixed-combination drops, particularly PGA-based fixed combinations, have recently been developed and used in patients with progression or who have failed to achieve their target IOPs. Here, we reviewed the current literature on the use of bimatoprost-timolol fixed combination (BTFC) in the People’s Republic of China. BTFC has achieved good efficacy and tolerability in Chinese clinical trials. In addition, BTFC is more cost effective compared with other fixed combinations available in the People’s Republic of China. Fixed-combination drops may offer benefits, such as keeping the ocular surface healthy, convenience of administration, and improvement in long-term adherence and quality of life. Therefore, BTFC has great potential for the treatment of Chinese glaucoma patients. However, the long-term efficacy of BTFC, comparisons of BTFC with other fixed-combination drugs, and treatment adherence and persistence with treatment in Chinese patients are unknown and will require further study. PMID:25999695

Combining naltrexone and prazosin in a single oral medication decreases alcohol drinking more effectively than does either drug alone.

PubMed

Froehlich, Janice C; Hausauer, Brett J; Rasmussen, Dennis D

2013-10-01

Naltrexone (NTX) is underutilized in clinical treatment settings because its efficacy is modest, and it is not effective for all alcoholics and, when it is effective, a significant number of alcoholics fail to maintain initial treatment gains and subsequently relapse to heavy drinking. This has slowed acceptance of NTX by the treatment community, and there is a clear need for additional treatments for alcoholism and alcohol use disorders. Given that NTX and prazosin can each reduce alcohol drinking in rats selectively bred for alcohol preference and high voluntary alcohol drinking (alcohol-preferring "P" rats), we tested whether a combination of NTX + prazosin is more effective in decreasing alcohol drinking than is either drug alone. P rats were given access to a 15% (v/v) alcohol solution for 2 hours daily. Rats were fed NTX and prazosin, alone or in combination, prior to onset of the daily 2-hour alcohol access period for 4 weeks and the effect of drug treatment on alcohol and water intake was assessed. During the first week of treatment, neither a low dose of NTX, nor prazosin, was effective in decreasing alcohol intake when each drug was administered alone, but combining the 2 drugs in a single medication significantly reduced alcohol intake. The combination was as effective as was a higher dose of NTX. Using a low dose of NTX in combination with prazosin may reduce the potential for undesirable side effects early in treatment which, in turn, may improve patient compliance and result in a more successful outcome when NTX is used for treating alcoholism and alcohol use disorders. Combining low-dose NTX and prazosin in a single medication may be more useful than is either drug alone for treating both inpatient and outpatient alcoholics and heavy drinkers early in the treatment process. Copyright © 2013 by the Research Society on Alcoholism.

Decontamination of Escherichia coli O157:H7 on green onions using pulsed light (PL) and PL-surfactant-sanitizer combinations.

PubMed

Xu, Wenqing; Chen, Haiqiang; Huang, Yaoxin; Wu, Changqing

2013-08-16

Imported green onion has been associated with three large outbreaks in the USA. Contamination has been found on both domestic and imported green onions. The objective of our study was to investigate Escherichia coli O157:H7 inactivation efficacy of pulsed light (PL) as well as its combination with surfactant and/or sanitizers on green onions. Green onions were cut into two segments, stems and leaves, to represent two different matrixes. Stems were more difficult to be decontaminated. Spot and dip inoculation methods were compared and dipped inoculated green onions were found to be more difficult to be decontaminated. Results showed that 5s dry PL (samples were not immersed in water during PL treatment) and 60s wet PL (samples were immersed in water and stirred during PL treatment) treatments provided promising inactivation efficacy (>4log10CFU/g) for spot inoculated stems and leaves. For dip inoculated green onions, 60s wet PL treatment was comparable with 100ppm chlorine washing, demonstrating that PL could be used as an alternative to chlorine. To further increase the degree of microbial inactivation, combined treatments were applied. PL combined with surfactant (SDS) was found to be more effective than single treatments of PL, SDS, chlorine, citric acid, thymol, and hydrogen peroxide, and binary combined treatments of PL with one of those chemicals. Addition of chlorine or hydrogen peroxide to the PL-SDS combination did not further enhanced its microbial inactivation efficacy. The combination of PL and 1000ppm of SDS reduced the E. coli O157:H7 populations dip inoculated on the stems and leaves of green onions by 1.4 and 3.1log10CFU/g, respectively. Our findings suggest that PL could potentially be used for decontamination of E. coli O157:H7 on green onions, with wet PL added with SDS being the most effective PL treatment. © 2013.

MDMA ("ecstasy"), methamphetamine and their combination: long-term changes in social interaction and neurochemistry in the rat.

PubMed

Clemens, Kelly J; Van Nieuwenhuyzen, Petra S; Li, Kong M; Cornish, Jennifer L; Hunt, Glenn E; McGregor, Iain S

2004-05-01

3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are illicit drugs that are increasingly used in combination. The acute and long-term effects of MDMA/METH combinations are largely uncharacterised. The current study investigated the behavioural, thermal and neurotoxic effects of MDMA and METH when given alone or in combined low doses. Male rats received four injections, one every 2 h, of vehicle, MDMA (2.5 or 5 mg/kg per injection), METH (2.5 or 5 mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per injection or 2+2 mg/kg per injection). Drugs were given at an ambient temperature of 28 degrees C to simulate hot nightclub conditions. Body temperature, locomotor activity and head-weaving were assessed during acute drug administration while social interaction, anxiety-related behavior on the emergence test and neurochemical parameters were assessed 4-7 weeks later. All treatments acutely increased locomotor activity, while pronounced head-weaving was seen with both MDMA/METH treatments and the higher dose METH treatment. Acute hyperthermia was greatest with the higher dose MDMA/METH treatment and was also seen with MDMA but not METH treatment. Several weeks after drug administration, both MDMA/METH groups, both METH groups and the higher dose MDMA group showed decreased social interaction relative to controls, while both MDMA/METH groups and the lower dose MDMA group showed increased anxiety-like behaviour on the emergence test. MDMA treatment caused 5-HT and 5-HIAA depletion in several brain regions, while METH treatment reduced dopamine in the prefrontal cortex. Combined MDMA/METH treatment caused 5-HT and 5-HIAA depletion in several brain regions and a unique depletion of dopamine and DOPAC in the striatum. These results suggest that MDMA and METH in combination may have greater adverse acute effects (head-weaving, body temperature) and long-term effects (decreased social interaction, increased emergence anxiety, dopamine depletion) than equivalent doses of either drug alone.

Feasibility Study Combining Art Therapy or Cognitive Remediation Therapy with Family-based Treatment for Adolescent Anorexia Nervosa.

PubMed

Lock, James; Fitzpatrick, Kathleen Kara; Agras, William S; Weinbach, Noam; Jo, Booil

2018-01-01

Adolescents with anorexia nervosa who have obsessive-compulsive (OC) features respond poorly to family-based treatment (FBT). This study evaluated the feasibility of combining FBT with either cognitive remediation therapy (CRT) or art therapy (AT) to improve treatment response in this at-risk group. Thirty adolescents with anorexia nervosa and OC features were randomized to 15 sessions of FBT + CRT or AT. Recruitment rate was 1 per month, and treatment attrition was 16.6% with no differences between groups. Suitability, expectancy and therapeutic relationships were acceptable for both combinations. Correlations between changes in OC traits and changes in cognitive inefficiencies were found for both combinations. Moderate changes in cognitive inefficiencies were found in both groups but were larger in the FBT + AT combination. This study suggests that an RCT for poor responders to FBT because of OC traits combining FBT with either CRT or AT is feasible to conduct. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Effect of combined topical heparin and steroid on corneal neovascularization in children.

PubMed

Michels, Rike; Michels, Stephan; Kaminski, Stephan

2012-01-01

To demonstrate the effect of topical heparin combined with topical steroid on corneal neovascularization (CN) in children. Four children (5 eyes) with new-onset progressive CN in at least one eye received topical rimexolone or dexamethasone in combination with heparin until complete regression of CN was obtained. The regression of CN was documented by slit-lamp or anterior segment photography. All 5 eyes showed complete regression of CN within 5 months. An anti-angiogenic effect was found as early as 1 week after starting topical combination treatment. No ocular and systemic side effects were detected and treatment was well tolerated by all children. In the 3 eyes with involvement of the optical axis, symmetrical visual acuity was obtained by amblyopia treatment. Recurrence of the CN was detectable in 2 eyes at 1 and 6 months, respectively, after ending combination therapy. Both eyes responded favorably to re-treatment. Combination of topical heparin and steroid leads to rapid regression and complete inactivity of CN. This therapeutic approach is promising, especially in children with limited therapeutic alternatives and a high risk for amblyopia. Copyright 2012, SLACK Incorporated.

Combinations of Drugs in the Treatment of Obesity

PubMed Central

Halpern, Bruno; Oliveira, Eduardo S. L.; Faria, André M.; Halpern, Alfredo; de Melo, Maria Edna; Cercato, Cintia; Mancini, Marcio C.

2010-01-01

Obesity is a chronic disease associated with excess morbidity and mortality. Clinical treatment, however, currently offers disappointing results, with very high rates of weight loss failure or weight regain cycles, and only two drugs (orlistat and sibutramine) approved for long-term use. Drugs combinations can be an option for its treatment but, although widely used in clinical practice, very few data are available in literature for its validation. Our review focuses on the rationale for their use, with advantages and disadvantages; on combinations often used, with or without studies; and on new perspectives of combinations being studied mainly by the pharmaceutical industry. PMID:27713360

Preliminary report on the efficiency of combined haemodialysis-haemoperfusion treatment in chronic uraemia.

PubMed

Albertazzi, A; Cappelli, P; Di Paolo, B; Evangelista, M

1984-01-01

The use of activated charcoal haemoperfusion can play a complementary role in the substitutive treatment of chronic uraemia. This study reports the preliminary results of a regular combined haemodialysis-haemoperfusion treatment. The effectiveness of this treatment was observed on the subjective symptomatology (anorexia, nausea, asthenia) and on the polyneuropathy evaluated by electrophysiological assessments. The biocompatability of the system proved satisfactory.

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)

Experiences and psychological distress of fertility treatment and employment.

PubMed

Payne, Nicola; Seenan, Susan; van den Akker, Olga

2018-04-16

This study examined experiences and psychological distress about fertility treatment in people combining work and treatment. Five hundred and sixty-three participants in the UK completed an online survey asking about difficulties in combining work and treatment; workplace disclosure, support, absence and policy; and psychological distress about treatment. Absence from work and perceptions that treatment has an impact on work and career prospects were reported by the majority of participants and this was related to the psychological distress of treatment. Around three quarters of participants disclosed to their employer and colleagues. The key reason for disclosure was needing to ask for absence from work and the main reason for non-disclosure was privacy. Workplace policy relating to managing fertility treatment and support from colleagues and their employer was related to reduced psychological distress but workplace policy was reported by less than one quarter of participants. Difficulties experienced in combining work and treatment suggest that support is needed. Specific workplace policy, guidance for supervisors and flexibility in fertility clinic times should help support employees during treatment and reduce psychological distress, thereby potentially influencing physical health and treatment outcomes.

Clinical efficacy and safety of chelation treatment with typical penicillamine in cross combination with DMPS repeatedly for Wilson's disease.

PubMed

Xu, San-Qing; Li, Xu-Fang; Zhu, Hui-Yun; Liu, Yan; Fang, Feng; Chen, Ling

2013-10-01

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.

Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

PubMed

Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

2004-12-01

Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

Addition of pimecrolimus cream 1% to a topical corticosteroid treatment regimen in paediatric patients with severe atopic dermatitis: a randomized, double-blind trial.

PubMed

Meurer, Michael; Eichenfield, Lawrence F; Ho, Vincent; Potter, Paul C; Werfel, Thomas; Hultsch, Thomas

2010-05-01

Pimecrolimus and topical corticosteroids (TCS) combination therapy may provide an alternative treatment for patients with severe atopic dermatitis (AD), with faster clearance of disease flares, consequently reducing the duration of TCS treatment. To assess the safety profile of pimecrolimus cream 1% combined with fluticasone versus fluticasone alone in paediatric patients with severe AD. Patients (n = 376) were randomized to a combination of pimecrolimus cream 1% with fluticasone or vehicle plus fluticasone for 4 weeks. The primary outcome measure was the frequency of clinically relevant pre-defined adverse events (AEs) associated with the topical use of corticosteroids in patients with severe AD. Erythematous rash was the only AE, occurring more frequently in the combination group, while there were no noticeable differences in the frequency of other AEs of clinical interest between treatment groups. Efficacy variables were comparable between the two groups. A trend for greater time to relapse was observed for the combination of pimecrolimus cream 1% with fluticasone in patients who were clear at the end of treatment, with a marked improvement in facial AD. In paediatric patients with severe AD the overall safety profile of pimecrolimus cream 1% combined with fluticasone was similar to that of fluticasone alone.

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

Bostroem, P.A.

In order to evaluate the therapeutic effects of metoprolol, nifedipine, and their combination, 11 patients with secondary angina pectoris and with thallium tomographic findings indicating coronary artery disease were studied before and after these three treatment regimes in a single-blind cross-over study. The therapeutic effect was measured by standardized working test and isotope angiocardiography, which enabled evaluation of left ventricular ejection fraction, stroke volume, and phase analysis of left ventricular contraction. Treatment with metoprolol and combination therapy increased work performance. Ejection fraction did not differentiate the treatment regimes, whereas stroke volume was significantly lower at work and heart rate highermore » at rest and at work during nifedipine treatment compared to either metoprolol or combination treatment (p less than 0.05). Cardiac output was significantly reduced during nifedipine and metoprolol treatment during work (p less than 0.05). Phase improved after all therapeutic regimes, but reached significance only during the metoprolol treatment period at rest (p less than 0.05).« less

TREATMENT OF STROKE WITH DETA-NONOATE AND BONE MARROW STROMAL CELLS UPREGULATES ANGIOPOIETIN-1/TIE2 AND ENHANCES NEOVASCULARIZATION

PubMed Central

CUI, X.; CHEN, J.; ZACHAREK, A.; ROBERTS, C.; SAVANT-BHONSALE, S.; CHOPP, M.

2008-01-01

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, DETA-NONOate and bone marrow stromal cells promote functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates Angiopoietin1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhances cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were intravenously administered PBS, bone marrow stromal cells 5×105, DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated Angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean ± SE, p<0.05). In vitro, DETA-NONOate significantly increased Angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased Angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (p<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cells conditioned medium compared with cells treated with bone marrow stromal cells conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that Angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared to vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of Angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the Angiopoietin-1/Tie2 axis. PMID:18691637

Review of the contemporary cytotoxic and biologic combinations available for the treatment of metastatic breast cancer.

PubMed

Tkaczuk, Katherine H Rak

2009-01-01

Treatment of metastatic breast cancer (MBC) with > or =2 chemotherapeutic agents concurrently has been shown to increase response rates, often at the cost of a substantial increase in toxicity, and with minimal impact on the overall survival. However, some combinations of the newer cytotoxic agents, as well as combinations of chemotherapeutic agents and targeted biologic anticancer agents, can produce synergistic efficacy with a manageable toxicity profile. The aims of this work were to provide an overview of the currently approved combination regimens available for the treatment of MBC and to consider the clinical data supporting other drug combinations that may supplement the current therapeutic choices in the near future. Literature searches were performed using MEDLINE/PubMed, with a focus on combination therapies for the treatment of MBC that are approved by the US Food and Drug Administration (FDA) or in Phase III clinical trials. The National Institutes of Health's Clinical Trial Registry was searched for relevant ongoing clinical trials in specific areas. Bibliographies were also searched for additional relevant material. Preference was given to recently published, larger, well-designed clinical trials that influence current prescribing practices. Phase I and II studies, and/or studies older than 10 years (ie, published earlier than 1999), were afforded less emphasis or were disregarded. Combinations of taxanes with capecitabine or gemcitabine, and ixabepilone plus capecitabine, are approved by the FDA as combination regimens for the treatment of MBC. The use of targeted therapies such as trastuzumab, bevacizumab, or lapatinib in combination with taxanes (for the former two) or capecitabine (for lapatinib) is also approved. Several investigational drug combinations are also currently undergoing evaluation in clinical trials, including combinations of bevacizumab and gemcitabine with capecitabine or alternative taxanes. Although results from Phase I and II studies are largely encouraging so far, the data from ongoing Phase III studies will ultimately dictate changes in clinical practice. It seems unlikely that any single agent or combination regimen will emerge as superior in all patients with MBC, given the heterogeneous nature of the disease and patient population. New combination regimens for MBC may broaden the range of treatment options currently available to delay disease progression for as long as possible. Copyright 2009 Excerpta Medica Inc. All rights reserved.

Long-term Safety and Efficacy of Mirabegron and Solifenacin in Combination Compared with Monotherapy in Patients with Overactive Bladder: A Randomised, Multicentre Phase 3 Study (SYNERGY II).

PubMed

Gratzke, Christian; van Maanen, Rob; Chapple, Christopher; Abrams, Paul; Herschorn, Sender; Robinson, Dudley; Ridder, Arwin; Stoelzel, Matthias; Paireddy, Asha; Yoon, Sang Jin; Al-Shukri, Salman; Rechberger, Tomasz; Mueller, Elizabeth R

2018-06-01

The long-term potential of solifenacin and mirabegron combination treatment for patients with overactive bladder (OAB) has not been previously assessed. To evaluate the safety and efficacy of solifenacin succinate 5mg plus mirabegron 50mg tablets (combination treatment) versus solifenacin or mirabegron monotherapy in patients with OAB over 12 mo. Randomised, double-blind, multicentre, phase 3 trial (SYNERGY II) of patients with "wet" OAB symptoms (urinary frequency and urgency with incontinence) for ≥3 mo. The study was conducted from March 2014 to September 2016; with 1829 patients randomised. The full analysis set was comprised of 1794 patients. The primary objective was safety, measured as treatment-emergent adverse events (TEAEs). Efficacy was measured as the change from baseline to the end of treatment in the mean number of incontinence episodes/24h and micturitions/24h. The median age was 60 yr (range 19-86 yr) and 1434 patients (80%) were female. Overall, 856 patients (47%) experienced ≥1 TEAE. TEAE frequency was slightly higher in the combination group (596 patients, 49%; mirabegron 126 patients, 41%; solifenacin 134 patients, 44%). Serious TEAEs were reported by 67 patients (3.7%); one was considered possibly treatment-related (mirabegron group, atrial fibrillation). Dry mouth was the most common TEAE (combination 74 patients, 6.1%; solifenacin 18 patients, 5.9%; mirabegron 12 patients, 3.9%). Combination therapy was statistically superior to mirabegron and solifenacin for the number of incontinence episodes (vs mirabegron: adjusted mean difference [AMD] -0.5, 95% confidence interval [CI] -0.7 to -0.2, p<0.001; vs solifenacin: AMD -0.1, 95% CI -0.4 to 0.1, p=0.002) and micturitions (vs mirabegron: AMD -0.5, 95% CI -0.8 to -0.2, p<0.001; vs solifenacin: AMD -0.4, 95% CI -0.7 to -0.1, p=0.004). Mirabegron and solifenacin combination treatment for OAB symptoms was well tolerated over 12 mo and led to efficacy improvements over each monotherapy. This innovative combination is a treatment option that could become widely used in the clinic. This study looked at the safety and efficacy of a combination of solifenacin succinate 5mg plus mirabegron 50mg tablets over 12 mo in patients with the overactive bladder (OAB) symptoms of increased urination frequency, heightened urgency to urinate, and unintentional passing of urine. We compared this treatment with solifenacin succinate 5mg or mirabegron 50mg alone, and found that the combination treatment was well tolerated by patients and led to greater improvements in symptoms. This novel combination could be an improved treatment option in the clinical setting for patients with OAB. This study is registered at ClinicalTrials.gov as NCT02045862. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

PubMed

Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

2017-03-01

In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a willingness-to-pay threshold of $100 000. In probabilistic sensitivity analysis, the combination of naloxone distribution, PrEP, and linkage to addiction treatment was the optimal strategy in 37% of iterations and the combination of naloxone distribution and linkage to addiction treatment was the optimal strategy in 34% of iterations. Naloxone distribution through syringe service programmes is cost-effective compared with syringe distribution alone, but when combined with linkage to addiction treatment is cost saving compared with no additional services. A strategy that combines naloxone distribution, PrEP, and linkage to addiction treatment results in greater health benefits in people who inject drugs and is also cost-effective. State of Connecticut Department of Public Health and the National Institute of Mental Health. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.

Sodium valproate and clonazepam for treatment-resistant panic disorder.

PubMed Central

Ontiveros, A; Fontaine, R

1992-01-01

Sodium valproate (VA) and clonazepam (CLZ) were combined in the treatment of 4 patients with panic disorders (PD) who were resistant to several antipanic drug treatments. A significant improvement was found in the symptomatology of these patients, but relapses occurred when CLZ dosage was reduced. A potentiation of the GABAergic properties of VA and clonazepam is postulated. This combined treatment could be advantageous for some treatment-resistant PD patients but needs to be studied further. PMID:1637803

Supervised exercises for adults with acute lateral ankle sprain: a randomised controlled trial

PubMed Central

van Rijn, Rogier M; van Os, Anton G; Kleinrensink, Gert-Jan; Bernsen, Roos MD; Verhaar, Jan AN; Koes, Bart W; Bierma-Zeinstra, Sita MA

2007-01-01

Background During the recovery period after acute ankle sprain, it is unclear whether conventional treatment should be supported by supervised exercise. Aim To evaluate the short- and long-term effectiveness of conventional treatment combined with supervised exercises compared with conventional treatment alone in patients with an acute ankle sprain. Design Randomised controlled clinical trial. Setting A total of 32 Dutch general practices and the hospital emergency department. Method Adults with an acute lateral ankle sprain consulting general practices or the hospital emergency department were allocated to either conventional treatment combined with supervised exercises or conventional treatment alone. Primary outcomes were subjective recovery (0–10 point scale) and the occurrence of a re-sprain. Measurements were carried out at intake, 4 weeks, 8 weeks, 3 months, and 1 year after injury. Data were analysed using intention-to-treat analyses. Results A total of 102 patients were enrolled and randomised to either conventional treatment alone or conventional treatment combined with supervised exercise. There was no significant difference between treatment groups concerning subjective recovery or occurrence of re-sprains after 3 months and 1-year of follow-up. Conclusion Conventional treatment combined with supervised exercises compared to conventional treatment alone during the first year after an acute lateral ankle sprain does not lead to differences in the occurrence of re-sprains or in subjective recovery. PMID:17925136

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.

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.

Combination of Pre-Treatment DWI-Signal Intensity and S-1 Treatment: A Predictor of Survival in Patients with Locally Advanced Pancreatic Cancer Receiving Stereotactic Body Radiation Therapy and Sequential S-1.

PubMed

Zhang, Yu; Zhu, Xiaofei; Liu, Ri; Wang, Xianglian; Sun, Gaofeng; Song, Jiaqi; Lu, Jianping; Zhang, Huojun

2018-04-01

To identify whether the combination of pre-treatment radiological and clinical factors can predict the overall survival (OS) in patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiation and sequential S-1 (a prodrug of 5-FU combined with two modulators) therapy with improved accuracy compared with that of established clinical and radiologic risk models. Patients admitted with LAPC underwent diffusion weighted imaging (DWI) scan at 3.0-T (b = 600 s/mm 2 ). The mean signal intensity (SI b = 600) of region-of-interest (ROI) was measured. The Log-rank test was done for tumor location, biliary stent, S-1, and other treatments and the Cox regression analysis was done to identify independent prognostic factors for OS. Prediction error curves (PEC) were used to assess potential errors in prediction of survival. The accuracy of prediction was evaluated by Integrated Brier Score (IBS) and C index. 41 patients were included in this study. The median OS was 11.7 months (2.8-23.23 months). The 1-year OS was 46%. Multivariate analysis showed that pre-treatment SI b = 600 value and administration of S-1 were independent predictors for OS. The performance of pre-treatment SI b = 600 and S-1 treatment in combination was better than that of SI b = 600 or S-1 treatment alone. The combination of pre-treatment SI b = 600 and S-1 treatment could predict the OS in patients with LAPC undergoing SBRT and sequential S-1 therapy with improved accuracy compared with that of established clinical and radiologic risk models. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Combination cisplatin and sulforaphane treatment reduces proliferation, invasion, and tumor formation in epidermal squamous cell carcinoma.

PubMed

Kerr, Candace; Adhikary, Gautam; Grun, Daniel; George, Nicholas; Eckert, Richard L

2018-01-01

Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet-derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma. Both agents suppress cell proliferation, growth of cancer stem cell spheroids, matrigel invasion and migration of SCC-13 and HaCaT cells, and combination treatment is more efficient. In addition, SCC-13 cell derived cancer stem cells are more responsive to these agents than non-stem cancer cells. Both agents suppress tumor formation, but enhanced suppression is observed with combined treatment. Moreover, both agents reduce the number of tumor-resident cancer stem cells. SFN treatment of cultured cells or tumors increases apoptosis and p21 Cip1 level, and both agents increase tumor apoptosis. We suggest that combined therapy with sulforaphane and cisplatin is efficient in suppressing tumor formation and may be a treatment option for advanced epidermal squamous cell carcinoma. © 2017 Wiley Periodicals, Inc.

Combination of UV-C treatment and Metschnikowia pulcherrimas for controlling Alternaria rot in postharvest winter jujube fruit.

PubMed

Guo, Dongqi; Zhu, Lixia; Hou, Xujie

2015-01-01

The potential of using antagonistic yeast Metschnikowia pulcherrimas alone or in combination with ultraviolet-C (UV-C) treatment for controlling Alternaria rot of winter jujube, and its effects on postharvest quality of fruit was investigated. The results showed that spore germination of Alternaria alternata was significantly inhibited by each of the 3 doses (1, 5, and 10 kJ m(-2) ) in vitro. In vivo, UV-C treatment (5 kJ m(-2) ) or antagonist yeast was capable of reducing the percentage of infected wounds and lesion diameter in artificially inoculated jujube fruits, however, in fruit treated with combination of UV-C treatment and M. pulcherrima, the percentage of infected wounds and lesion diameter was only 16.0% and 0.60 cm, respectively. The decay incidence on winter jujube fruits treated with the combination of UV-C treatment and M. pulcherrima was 23% after storage at 0 ± 1 °C for 45 d followed by 22 °C for 7 d. None of the treatments impaired quality parameters of jujube fruit. Thus, the combination of UV-C radiation and M. pulcherrima could be an alternative to synthetic fungicides for controlling postharvest Alternaria rot of winter jujube. © 2014 Institute of Food Technologists®

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

PubMed

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

2016-07-01

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

Efficacy of Punch Elevation Combined with Fractional Carbon Dioxide Laser Resurfacing in Facial Atrophic Acne Scarring: A Randomized Split-face Clinical Study

PubMed Central

Faghihi, Gita; Nouraei, Saeid; Asilian, Ali; Keyvan, Shima; Abtahi-Naeini, Bahareh; Rakhshanpour, Mehrdad; Nilforoushzadeh, Mohammad Ali; Hosseini, Sayed Mohsen

2015-01-01

Background: A number of treatments for reducing the appearance of acne scars are available, but general guidelines for optimizing acne scar treatment do not exist. The aim of this study was to compare the clinical effectiveness and side effects of fractional carbon dioxide (CO2) laser resurfacing combined with punch elevation with fractional CO2 laser resurfacing alone in the treatment of atrophic acne scars. Materials and Methods: Forty-two Iranian subjects (age range 18–55) with Fitzpatrick skin types III to IV and moderate to severe atrophic acne scars on both cheeks received randomized split-face treatments: One side received fractional CO2 laser treatment and the other received one session of punch elevation combined with two sessions of laser fractional CO2 laser treatment, separated by an interval of 1 month. Two dermatologists independently evaluated improvement in acne scars 4 and 16 weeks after the last treatment. Side effects were also recorded after each treatment. Results: The mean ± SD age of patients was 23.4 ± 2.6 years. Clinical improvement of facial acne scarring was assessed by two dermatologists blinded to treatment conditions. No significant difference in evaluation was observed 1 month after treatment (P = 0.56). Their evaluation found that fractional CO2 laser treatment combined with punch elevation had greater efficacy than that with fractional CO2 laser treatment alone, assessed 4 months after treatment (P = 0.02). Among all side effects, coagulated crust formation and pruritus at day 3 after fractional CO2 laser treatment was significant on both treatment sides (P < 0.05). Conclusion: Concurrent use of fractional laser skin resurfacing with punch elevation offers a safe and effective approach for the treatment of acne scarring. PMID:26538695

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

PubMed Central

Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

2016-01-01

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

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

PubMed

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

2015-05-01

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

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.

Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

PubMed Central

Bondarenko, Maryna; Laluce, Nahuel Cesatti; Rozados, Viviana; Nicolas, André; Carré, Manon; Scharovsky, O. Graciela; Márquez, Mauricio Menacho

2017-01-01

Discovery of new drugs for cancer treatment is an expensive and time-consuming process and the percentage of drugs reaching the clinic remains quite low. Drug repositioning refers to the identification and development of new uses for existing drugs and represents an alternative drug development strategy. In this work, we evaluated the antitumor effect of metronomic treatment with a combination of two repositioned drugs, metformin and propranolol, in triple negative breast cancer models. By in vitro studies with five different breast cancer derived cells, we observed that combined treatment decreased proliferation (P < 0.001), mitochondrial activity (P < 0.001), migration (P < 0.001) and invasion (P < 0.001). In vivo studies in immunocompetent mice confirmed the potential of this combination in reducing tumor growth (P < 0.001) and preventing metastasis (P < 0.05). Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity. PMID:27926515

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

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

On the vicissitudes of combining individual and group psychotherapy.

PubMed

Schermer, Victor L

2009-01-01

Abstract Reviewing a series of articles in this special issue on combined treatment incorporating individual and group therapy, and in one instance couples therapy and a relationship group, the author provides a synoptic history of combined treatment, noting that the relational perspectives of psychoanalysis and systems theories of groups now provide conceptual frameworks for combined therapies. Taking up each article in turn, he considers that combined treatment poses particular problems while having certain advantages. He discusses the theoretical emphases and biases of each article, whether relational psychology, classical psychoanalysis, object relations theory, or self-psychology. He considers the roles of transference and countertransference, patient-therapist enactments, empathic attunement, "surrogate therapy" by the group members, and ethics in determining outcomes. In addition, the author notes how so-called difficult or regressed patients impact upon and are affected by the use of combined therapy modalities.

Combined effects of lanthanum (III) chloride and acid rain on photosynthetic parameters in rice.

PubMed

Wang, Lihong; Wang, Wen; Zhou, Qing; Huang, Xiaohua

2014-10-01

Rare earth elements (REEs) pollution and acid rain are environmental issues, and their deleterious effects on plants attract worldwide attention. These two issues exist simultaneously in many regions, especially in some rice-growing areas. However, little is known about the combined effects of REEs and acid rain on plants. Here, the combined effects of lanthanum chloride (LaCl3), one type of REE salt, and acid rain on photosynthesis in rice were investigated. We showed that the combined treatment of 81.6 μM LaCl3 and acid rain at pH 4.5 increased net photosynthetic rate (Pn), stomatic conductance (Gs), intercellular CO2 concentration (Ci), Hill reaction activity (HRA), apparent quantum yield (AQY) and carboxylation efficiency (CE) in rice. The combined treatment of 81.6 μM LaCl3 and acid rain at pH 3.5 began to behave toxic effects on photosynthesis (decreasing Pn, Gs, HRA, AQY and CE, and increasing Ci), and the maximally toxic effects were observed in the combined treatment of 2449.0 μM LaCl3 and acid rain at pH 2.5. Moreover, the combined effects of LaCl3 and acid rain on photosynthesis in rice depended on the growth stage of rice, with the maximal effects occurring at the booting stage. Furthermore, the combined treatment of high-concentration LaCl3 and low-pH acid rain had more serious effects on photosynthesis in rice than LaCl3 or acid rain treatment alone. Finally, the combined effect of LaCl3 and acid rain on Pn in rice resulted from the changes in stomatic (Gs, Ci) and non-stomatic (HRA, AQY and CE) factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Complex treatment of tobacco dependence by means of psychotherapeutic correction in combination with mesodiencephalic modulation in patients with chronic diseases of digestive organs].

PubMed

Rassulova, M A; Safonova, O V; Ksenofontova, I V; Firsova, L D

2010-01-01

This paper deals with the problem of tobacco dependence and its medical treatment. Various methods available for this purpose are considered with special reference to their clinical efficiency. A scheme for combined treatment of the given pathology is proposed.

Development of a biocidal treatment regime to inhibit biological growths on cultural heritage: BIODAM

NASA Astrophysics Data System (ADS)

Young, M. E.; Alakomi, H.-L.; Fortune, I.; Gorbushina, A. A.; Krumbein, W. E.; Maxwell, I.; McCullagh, C.; Robertson, P.; Saarela, M.; Valero, J.; Vendrell, M.

2008-12-01

Existing chemical treatments to prevent biological damage to monuments often involve considerable amounts of potentially dangerous and even poisonous biocides. The scientific approach described in this paper aims at a drastic reduction in the concentration of biocide applications by a polyphasic approach of biocides combined with cell permeabilisers, polysaccharide and pigment inhibitors and a photodynamic treatment. A variety of potential agents were screened to determine the most effective combination. Promising compounds were tested under laboratory conditions with cultures of rock deteriorating bacteria, algae, cyanobacteria and fungi. A subsequent field trial involved two sandstone types with natural biofilms. These were treated with multiple combinations of chemicals and exposed to three different climatic conditions. Although treatments proved successful in the laboratory, field trials were inconclusive and further testing will be required to determine the most effective treatment regime. While the most effective combination of chemicals and their application methodology is still being optimised, results to date indicate that this is a promising and effective treatment for the control of a wide variety of potentially damaging organisms colonising stone substrates.

Biomechanical evaluation of the natural abutment teeth in combined tooth-implant-supported telescopic prostheses: a three-dimensional finite element analysis.

PubMed

Chen, Yu; Wang, Chao; Huang, Yuanding; Feng, Tianming; Zou, Huawei; Fan, Yubo

2017-07-01

Telescopic overdentures supported by the combination of natural teeth and implants have been thought a valuable treatment for the severely compromised partially edentulous patients. But the combination of teeth and implants involves highly complex biomechanical problems. This study is to evaluate biomechanical behaviors of the natural abutment teeth with the treatment of combined tooth-implant supported telescopic crown prostheses in mandible through 3D FEA. According to this study, the prosthetic option supported by a combination of teeth and implants and retained by double crowns could protect teeth and their periodontal support tissues acting as a rigid splint, and may be a valuable treatment option for partially edentulous patients with severely reduced remaining teeth in mandible.

Efficacy of 694-nm fractional Q-switched ruby laser (QSRL) combined with sonophoresis on levorotatory vitamin C for treatment of melasma in Chinese patients.

PubMed

Zhou, H L; Hu, B; Zhang, C

2016-07-01

Melasma is a common acquired and distressing pigmentary disorder presenting to dermatology clinics. It is notably difficult to cure and has a tendency to relapse. The efficacy of classical Q-switched laser in treatment of melasma remains controversial. This study aims to investigate the efficacy and safety of 694-nm fractional QSRL combined with sonophoresis on levorotatory vitamin C for the treatment of melasma patients. Twenty-six patients with melasma were enrolled. Each patient received four to six fractional QSRL treatments at pulse energies of 2.5 to 4 J/cm(2) combined with sonophoresis on levorotatory vitamin C at 2-week intervals. The severity and the area of melasma were assessed by two investigators using the melasma area and severity index (MASI). Side effects were documented. Mean MASI score decreased from 15.51 ± 3.00 before treatment to 10.02 ± 4.39 3 months after the final treatment (P < 0.01). Side effects were few and transient. High-density coverage fractional QSRL combined with sonophoresis on levorotatory vitamin C is safe and effective for the treatment of melasma in Chinese patients.

Neonatal Abstinence Syndrome (NAS): Transitioning Methadone Treated Infants From An Inpatient to an Outpatient Setting

PubMed Central

Backes, Carl H.; Backes, Carl R.; Gardner, Debra; Nankervis, Craig A.; Giannone, Peter J.; Cordero, Leandro

2013-01-01

Background Each year in the US approximately 50,000 neonates receive inpatient pharmacotherapy for the treatment of neonatal abstinence syndrome (NAS). Objective To compare the safety and efficacy of a traditional inpatient only approach with a combined inpatient and outpatient methadone treatment program. Design/Methods Retrospective review (2007-9). Infants were born to mothers maintained on methadone or buprenorphine in an antenatal substance abuse program. All infants received methadone for NAS treatment as inpatient. Methadone weaning for the traditional group (75 pts) was inpatient while the combined group (46 pts) was outpatient. Results Infants in the traditional and combined groups were similar in demographics, obstetrical risk factors, birth weight, GA and the incidence of prematurity (34 & 31%). Hospital stay was shorter in the combined than in the traditional group (13 vs 25d; p < 0.01). Although the duration of treatment was longer for infants in the combined group (37 vs 21d, p<0.01), the cumulative methadone dose was similar (3.6 vs 3.1mg/kg, p 0.42). Follow-up: Information was available for 80% of infants in the traditional and 100% of infants in the combined group. All infants in the combined group were seen ≤ 72 hours from hospital discharge. Breast feeding was more common among infants in the combined group (24 vs. 8% p<0.05). Following discharge there were no differences between the two groups in hospital readmissions for NAS. Prematurity (<37w GA) was the only predictor for hospital readmission for NAS in both groups (p 0.02, OR 5). Average hospital cost for each infant in the combined group was $13,817 less than in the traditional group. Conclusions A combined inpatient and outpatient methadone treatment in the management of NAS decreases hospital stay and substantially reduces cost. Additional studies are needed to evaluate the potential long term benefits of the combined approach on infants and their families. PMID:21852772

[Physical factors in the treatment of patients with osteoarthrosis and venous insufficiency].

PubMed

Tereshina, L G; Oranskiĭ, I E; Kozlova, L A; Veselkova, E E

1995-01-01

Comparative evaluation of two variants of multiple modality treatment for osteoarthritis gives preference to combination of decimetric wave radiation and effervescent baths over magnetotherapy combination with effervescent baths.

New Combinational Method for Noninvasive Treatments of Superficial Tissues for Body Aesthetics Applications

NASA Astrophysics Data System (ADS)

Rybyanets, A. N.; Naumenko, A. A.

The paper introduces an innovative combinational treatment method based on ultrasonic standing waves (USW) technology for noninvasive surgical, therapeutic, lypolitic or cosmetic treatment of tissues including subcutaneous adipose tissue, cellulite or skin on arbitrary body part of patient. The method is based on simultaneous or successive applying of constructively interfering physically and biologically sensed influences: USW, ultrasonic shear waves, radio-frequency (RF) heating, and vacuum massage. The paper provides basic physical principles of USW as well as critical comparison of USW and HIFU methods. The results of finite-elements and finite- difference modeling of USW transducer design and nodal pattern structure in tissue are presented. Biological effects of USW-tissue interaction and synergetic aspects of USW and RF combination are explored. Combinational treatment transducer designs and original in-vitro experiments on tissues are described.

Synergistic effect of eribulin and CDK inhibition for the treatment of triple negative breast cancer.

PubMed

Rao, Shreyas S; Stoehr, Jenna; Dokic, Danijela; Wan, Lei; Decker, Joseph T; Konopka, Kristine; Thomas, Alexandra L; Wu, Jia; Kaklamani, Virginia G; Shea, Lonnie D; Jeruss, Jacqueline S

2017-10-13

Activation of CDK2 in triple negative breast cancer (TNBC) can contribute to non-canonical phosphorylation of a TGFβ signaling component, Smad3, promoting cell proliferation and migration. Inhibition of CDK2 was shown to decrease breast cancer oncogenesis. Eribulin chemotherapy was used effectively in the treatment of TNBC. To this end, we tested therapeutic efficacy of a novel CDK2/9 inhibitor, CYC065, eribulin, and the combination of CYC065 and eribulin in 3 different TNBC cell lines, and an in vivo xenograft model. Specifically, we characterized cell proliferation, apoptosis, migration, cell cycle associated protein expression, treatment-related transcription factor activity, and tumor growth in TNBC. Treatment with CYC065 and eribulin in combination had a superior effect on decreasing cell proliferation, inducing apoptosis, and inhibiting migration in TNBC cell lines in vitro . Combination therapy inhibited non-canonical Smad3 phosphorylation at the T179 site in the protein linker region, and resulted in increased p15 and decreased c-myc expression. In a transcription factor array, combination treatment significantly increased activity of AP1 and decreased activity of factors including NFκB, SP1, E2F, and SMAD3. In an in vivo xenograft model of TNBC, individual and combination treatments resulted in a decrease in both tumor volume and mitotic indices. Taken together, these studies highlight the potential of this novel drug combination, CYC065 and eribulin, to suppress the growth of TNBC cells in vitro and in vivo, warranting further clinical investigation.

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

PubMed Central

2012-01-01

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

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.

Endovascular Treatments in Combination with Extracranial-Intracranial Bypass for Complex Intracranial Aneurysms.

PubMed

Sato, Kenichi; Endo, Hidenori; Fujimura, Miki; Endo, Toshiki; Matsumoto, Yasushi; Shimizu, Hiroaki; Tominaga, Teiji

2018-05-01

Although most intracranial aneurysms can be treated with microsurgery or endovascular procedure alone, a subset of aneurysms may require a combined approach. The purpose of this study was to assess the efficacy of endovascular interventions combined with bypass surgery for the treatment of complex intracranial aneurysms. We retrospectively reviewed medical records from a prospectively maintained patient database to identify patients who underwent endovascular treatment of an intracranial aneurysm at our institutes between 2007 and 2017. We recruited patients who received a preplanned combination of endovascular treatment and extracranial-intracranial bypass surgery. Forty-four patients (44 aneurysms) were treated with a combined approach. Twenty-four patients presented with subarachnoid hemorrhage. Treatment strategies included endovascular parent artery occlusion with the bypass surgery to restore cerebral blood flow (n = 12), endovascular trapping with bypass surgery to isolate incorporated branches (n = 12), and intra-aneurysmal coil embolization with bypass surgery to isolate incorporated branches (n = 20). During a mean period of 35.6 months, follow-up catheter angiography was performed in 35 of 44 patients (79.5%) and demonstrated complete aneurysm obliteration in 29 patients (82.9%) and bypass patency in 33 (94.3%). The postoperative aneurysm-related mortality and morbidity rates were 6.8% and 13.6%, respectively. Combined endovascular and surgical bypass procedures are useful for the treatment of complex intracranial aneurysms when conventional surgical or endovascular techniques are not feasible and show acceptable rates of morbidity and mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

Efficacy of combination of glycolic acid peeling with topical regimen in treatment of melasma.

PubMed

Chaudhary, Savita; Dayal, Surabhi

2013-10-01

Various treatment modalities are available for management of melasma, ranging from topical and oral to chemical peeling, but none is promising alone. Very few studies are available regarding efficacy of combination of topical treatment with chemical peeling. Combination of chemical peeling and topical regimen can be a good treatment modality in the management of this recalcitrant disorder. To assess the efficacy of combination of topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling in the treatment of melasma in Indian patients. Forty Indian patients of moderate to severe epidermal variety melasma were divided into two groups of 20 each. One Group i.e. peel group received topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling and other group i.e. control group received topical regimen (2% hydroquinone, 1% hydrocortisone, 0.05% tretinoin). There was an overall decrease in MASI from baseline in 24 weeks of therapy in both the groups (P value < 0.05). The group receiving the glycolic acid peel with topical regimen showed early and greater improvement than the group which was receiving topical regimen only. This study concluded that combining topical regimen (2% hydroquinone, 1% hydrocortisone and 0.05% tretinoin) with serial glycolic acid peeling significantly enhances the therapeutic efficacy of glycolic acid peeling. The combination of glycolic acid peeling with the topical regimen is a highly effective, safe and promising therapeutic option in treatment of melasma.

Efficacy Evaluation of Fungus Syncephalastrum racemosum and Nematicide Avermectin against the Root-Knot Nematode Meloidogyne incognita on Cucumber

PubMed Central

Huang, Wen-Kun; Sun, Jian-Hua; Cui, Jiang-Kuan; Wang, Gang-Feng; Kong, Ling-An; Peng, Huan; Chen, Shu-Long; Peng, De-Liang

2014-01-01

The root-knot nematode (RKN) is one of the most damaging agricultural pests.Effective biological control is need for controlling this destructive pathogen in organic farming system. During October 2010 to 2011, the nematicidal effects of the Syncephalastrum racemosum fungus and the nematicide, avermectin, alone or combined were tested against the RKN (Meloidogyne incognita) on cucumber under pot and field condition in China. Under pot conditions, the application of S. racemosum alone or combined with avermectin significantly increased the plant vigor index by 31.4% and 10.9%, respectively compared to the M. incognita-inoculated control. However, treatment with avermectin alone did not significantly affect the plant vigor index. All treatments reduced the number of root galls and juvenile nematodes compared to the untreated control. Under greenhouse conditions, all treatments reduced the disease severity and enhanced fruit yield compared to the untreated control. Fewer nematodes infecting plant roots were observed after treatment with avermectin alone, S. racemosum alone or their combination compared to the M. incognita-inoculated control. Among all the treatments, application of avermectin or S. racemosum combined with avermectin was more effective than the S. racemosum treatment. Our results showed that application of S. racemosum combined with avermectin not only reduced the nematode number and plant disease severity but also enhanced plant vigor and yield. The results indicated that the combination of S. racemosum with avermectin could be an effective biological component in integrated management of RKN on cucumber. PMID:24586982

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots.

PubMed

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants.

Combined Effects of Lanthanum (III) and Acid Rain on Antioxidant Enzyme System in Soybean Roots

PubMed Central

Zhang, Xuanbo; Du, Yuping; Wang, Lihong; Zhou, Qing; Huang, Xiaohua; Sun, Zhaoguo

2015-01-01

Rare earth element pollution (REEs) and acid rain (AR) pollution simultaneously occur in many regions, which resulted in a new environmental issue, the combined pollution of REEs and AR. The effects of the combined pollution on the antioxidant enzyme system of plant roots have not been reported. Here, the combined effects of lanthanum ion (La3+), one type of REE, and AR on the antioxidant enzyme system of soybean roots were investigated. In the combined treatment of La3+ (0.08 mM) and AR, the cell membrane permeability and the peroxidation of cell membrane lipid of soybean roots increased, and the superoxide dismutase, catalase, peroxidase and reduced ascorbic acid served as scavengers of reactive oxygen species. In other combined treatments of La3+ (0.40 mM, 1.20 mM) and AR, the membrane permeability, malonyldialdehyde content, superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content increased, while the catalase activity decreased. The increased superoxide dismutase activity, peroxidase activity and reduced ascorbic acid content were inadequate to scavenge the excess hydrogen peroxide and superoxide, leading to the damage of the cell membrane, which was aggravated with the increase in the concentration of La3+ and the level of AR. The deleterious effects of the combined treatment of La3+ and AR were stronger than those of the single treatment of La3+ or AR. Moreover, the activity of antioxidant enzyme system in the combined treatment group was affected directly and indirectly by mineral element content in soybean plants. PMID:26230263

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

PubMed

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

2013-05-01

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

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

PubMed Central

Chen, Xiwei; Yu, Jihnhee

2014-01-01

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

Evaluation of a biological wastewater treatment system combining an OSA process with ultrasound for sludge reduction.

PubMed

Romero-Pareja, P M; Aragon, C A; Quiroga, J M; Coello, M D

2017-05-01

Sludge production is an undesirable by-product of biological wastewater treatment. The oxic-settling-anaerobic (OSA) process constitutes one of the most promising techniques for reducing the sludge produced at the treatment plant without negative consequences for its overall performance. In the present study, the OSA process is applied in combination with ultrasound treatment, a lysis technique, in a lab-scale wastewater treatment plant to assess whether sludge reduction is enhanced as a result of mechanical treatment. Reported sludge reductions of 45.72% and 78.56% were obtained for the two regimes of combined treatment tested in this study during two respective stages: UO1 and UO2. During the UO1 stage, the general performance and nutrient removal improved, obtaining 47.28% TN removal versus 21.95% in the conventional stage. However, the performance of the system was seriously damaged during the UO2 stage. Increases in dehydrogenase and protease activities were observed during both stages. The advantages of the combined process are not necessarily economic, but operational, as US treatment acts as contributing factor in the OSA process, inducing mechanisms that lead to sludge reduction in the OSA process and improving performance parameters. Copyright © 2016 Elsevier B.V. All rights reserved.

Field testing of a fenbendazole treatment combined with hygienic and management measures against a natural Giardia infection in calves.

PubMed

Geurden, Thomas; Vercruysse, Jozef; Claerebout, Edwin

2006-12-20

The need of a combination of animal treatment and environmental measures against a natural Giardia infection in calves between the age of 1 and 6 months was emphasized and evaluated. Ten commercial farms with a total of 94 calves suffering from chronic diarrhea, ill thriving and impaired growth, were included in two subsequent studies. The first study indicated that treatment of all animals with fenbendazole at 15 mg/kg during 3 consecutive days combined with environmental measures on the final day of treatment, which were either removal of bedding, thorough cleaning and ammonia 10% disinfection or relocation of the treated animals to a Giardia free environment, resulted in a total reduction in cyst excretion for at least 2 weeks. In the second study, the immunofluorescence assay (Merifluor Cryptosporidium/Giardia; Meridian Diagnostics Inc., Cincinnati, Ohio) was used quantitatively and confirmed that the combination of treatment and environmental measures resulted in a total reduction of cyst excretion during 2 weeks and in a significant (P<0.05; >or=98.0%) reduction of the cyst excretion until at least 4 weeks after treatment. Furthermore, there was a noticeable improvement of the clinical symptoms in all animals towards day 28 after treatment and 4 months after treatment health in all calves was normal.

Chinese Herbal Medicine for Postpartum Depression: A Systematic Review of Randomized Controlled Trials

PubMed Central

Li, Yongle; Chen, Zijie; Yu, Ning; Yao, Keyu; Che, Yiwen; Xi, Yupeng

2016-01-01

Background. Postpartum depression (PPD) does great harm to women following childbirth. The aim of this study was to conduct a systematic review of the literature to assess the efficacy and safety of CHM for the treatment of PPD. Methods. Published or ongoing registered trials were searched for from the inception of the various databases to December 31, 2015. Data extraction and methodology assessment were conducted independently by two researchers. RevMan 5.3 software was used to analyze the data. Results. Forty-seven registered clinical trials (RCTs) were identified and reviewed. The results showed CHM alone or in combination with routine treatments could reduce HAMD score, EPDS score, incidence of adverse events, TESS, and SERS. CHM combined with routine treatment was more effective in increasing serum estradiol levels and reducing progesterone levels than routine treatment alone. Meanwhile, pooled data revealed that MRLQS combined with routine treatments or MRLQS plus MSHS combined with routine treatments were more effective than other therapeutic methods in TCM. MRLQS plus MSHS alone was found to be an effective alternative when compared to routine treatments. Conclusions. This review suggested that CHM was safe and effective in the treatment of PPD. However, this could not be proven conclusively. To ensure evidence-based clinical practice, more rigorously designed trials are warranted. PMID:27774110

Femara® and the future: tailoring treatment and combination therapies with Femara

PubMed Central

Ma, Cynthia

2007-01-01

Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs. PMID:17912640

The theoretical foundation and research progress for WBRT combined with erlotinib for the treatment of multiple brain metastases in patients with lung adenocarcinoma.

PubMed

Zhuang, Hongqing; Wang, Jun; Zhao, Lujun; Yuan, Zhiyong; Wang, Ping

2013-11-15

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung adenocarcinoma, and a theoretical basis exists for utilising whole brain radiotherapy (WBRT) combined with erlotinib for the treatment for brain metastases in patients with lung adenocarcinoma. This therapeutic regimen has the potential to be a revolutionary treatment for which the most appropriate indication is lung adenocarcinoma. Currently, there is no difference in the treatment of brain metastasis, especially multiple brain metastases, in patients with lung adenocarcinoma of patients with other lung carcinomas. Furthermore, limited clinical trials that combine a TKI with WBRT to treat multiple lung adenocarcinoma metastases have been conducted, and many clinical questions remain unanswered. Lung adenocarcinoma has a high propensity to metastasize to the brain, and targeted therapy has been widely used; however, clinical trials are necessary to provide data to support the combination of erlotinib and WBRT. Copyright © 2013 UICC.

Transvenous Endovascular Treatment for Scalp Arteriovenous Fistulas: Results with Combined Use of Onyx and Coils.

PubMed

Ni, Wei; Tian, Yanlong; Gu, Yuxiang; Mao, Ying

2017-11-01

Scalp arteriovenous fistulas (AVFs) are rare lesions that may occur spontaneously or secondary to head trauma. A standard treatment strategy for these lesions has not been established to date. We present 3 cases of successful treatment of scalp AVFs using a combination of Onyx-18 and coils via a transvenous approach. The patient database at Huashan Hospital, Fudan University, Shanghai, China was reviewed, and patients with scalp AVFs treated with Onyx-18 and coils via a transvenous approach were identified for analysis. Between 2014 and 2016, 3 consecutive patients with scalp AVFs were treated transvenously with Onyx embolization in combination with coil placement at our hospital. No procedure-related complications were noted. Postembolization angiography demonstrated successful and complete occlusion of the AVFs immediately after treatment. Clinical follow-up showed resolution of symptoms. The technique of transvenous "armored concrete" embolization using a combination of coils and Onyx is an effective treatment modality for scalp AVFs, particularly in type C cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Enhanced high-energy protocol using a fractional bipolar radiofrequency device combined with bipolar radiofrequency and infrared light for improving facial skin appearance and wrinkles.

PubMed

Gold, Michael H; Biesman, Brian S; Taylor, Mark

2017-06-01

Fractional bipolar radiofrequency treatment and treatment with bipolar radiofrequency combined with infrared light have been shown in previous trials to safely and effectively improve the appearance of facial wrinkles. To evaluate a high-energy protocol with combined bipolar radiofrequency and infrared light energies for improvement in photoaged facial skin. Seventy-two patients presenting with mild to moderate facial wrinkles underwent a single full-face treatment (n=54) or two treatments (n=18) at 6-week intervals. Independent blinded assessment and investigator assessment were performed, using the Fitzpatrick Wrinkle and Elastosis Scale (0-9) and the Global Aesthetic Improvement scale. Patients also completed a self-assessment questionnaire concerning satisfaction with the treatment. All patients achieved some degree of improvement in their wrinkles and skin appearance, following a single treatment or two treatments with the enhanced-energy protocol. Blinded evaluation demonstrated 71% and 70% of the patients showing improvement of one unit or greater on the Fitzpatrick Scale, at the 12-week and 24-week follow-ups post-treatment, respectively. Similar results were reported by investigators. Under the Global Aesthetic Improvement Scale, investigators observed 87%, 91% and 81% of patients showing improvement at the 6-, 12-, and 24-week post-treatment end, respectively. Patients tolerated the treatments well and were satisfied with the clinical results. The enhanced-energy treatment protocol, with fractional bipolar radiofrequency treatment and treatment with bipolar radiofrequency combined with infrared light applications, yields significant improvement of skin texture, wrinkling, and overall appearance following a single treatment. The results appear gradually over time and are maintained for at least 6 months' post-treatment. © 2017 Wiley Periodicals, Inc.

Jianpi Bushen, a Traditional Chinese Medicine Therapy, Combined with Chemotherapy for Gastric Cancer Treatment: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Chen, Yunbo; Zhang, Guijuan; Chen, Xiaoping; Jiang, Xuefeng; Yuan, Naijun; Wang, Yurong; Hao, Xiaoqian

2018-01-01

Objective. To investigate the effects of Jianpi Bushen (JPBS), a traditional Chinese medicine that is used to invigorate the spleen and tonify the kidney, combined with chemotherapy for the treatment of gastric cancer. Methods. Literature retrieval was performed in PubMed, EMBASE, Cochrane Library, MEDLINE, CNKI, Wanfang Data Information Site, and VIP from inception to October 2017. Randomized controlled trials to evaluate the effects of JPBS combined with chemotherapy were identified. The primary reported outcomes were KPS (Karnofsky Performance Status), clinical curative efficiency, immune function, blood system, and nonhematologic system. Review Manager 5.3 (RevMan 5.3) was used for data analysis, and the quality of the studies was also appraised. Results. A total of 26 studies were included with 3098 individuals. The results of the meta-analysis indicated that treatment of gastric cancer with the combination of JPBS and chemotherapy resulted in better outcomes compared to chemotherapy alone. Conclusion. Evidence from the meta-analysis suggested that JPBS combined with chemotherapy has a positive effect on gastric cancer treatment. However, additional rigorously designed and large sample randomized controlled trials are required to confirm the efficacy and safety of this treatment. PMID:29675052

Efficacy of IPL device combined with intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with regards to the recovery of skin barrier function: A pilot study.

PubMed

Kim, Dong Young; Park, Hyun Sun; Yoon, Hyun-Sun; Cho, Soyun

2015-10-01

Keloids and hypertrophic scars are prevalent and psychologically distressful dermatologic conditions. Various treatment modalities have been tried but without complete success by any one method. We evaluated the efficacy of a combination of intense pulsed light (IPL) device and intralesional corticosteroid injection for the treatment of keloids and hypertrophic scars with respect to the recovery of skin barrier function. Totally 52 Korean patients were treated by the combined treatment at 4-8-week intervals. Using digital photographs, changes in scar appearance were assessed with modified Vancouver Scar Scale (MVSS), physicians' global assessment (PGA) and patient's satisfaction score. In 12 patients, the stratum corneum (SC) barrier function was assessed by measuring transepidermal water loss (TEWL) and SC capacitance. Most scars demonstrated significant clinical improvement in MVSS, PGA and patient's satisfaction score after the combined therapy. A significant decrease of TEWL and elevation of SC capacitance were also documented after the treatment. The combination therapy (IPL + corticosteroid injection) not only improves the appearance of keloids and hypertrophic scars but also increases the recovery level of skin hydration status in terms of the skin barrier function.

Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells.

PubMed

Li, Xu; Zhu, Feng; Jiang, Jianxin; Sun, Chengyi; Wang, Xin; Shen, Ming; Tian, Rui; Shi, Chengjian; Xu, Meng; Peng, Feng; Guo, Xingjun; Wang, Min; Qin, Renyi

2015-02-01

Application of oxaliplatin for the treatment of pancreatic cancer (PC) is restricted owing to its toxic side effects and drug resistance. We investigated how withaferin A (WA), a bioactive component isolated from the medicinal plant Withania somnifera, acts synergistically with oxaliplatin on human PC in vitro and in vivo. We found that WA enhanced oxaliplatin-induced growth suppression and apoptosis in PC cells dramatically through a mechanism involving mitochondrial dysfunction and inactivation of the PI3K/AKT pathway. Combination treatment resulted in significant accumulation of intracellular reactive oxygen species (ROS). Pretreatment of cells with the ROS scavenger N-acetylcysteine completely blocked the apoptosis induced by combination treatment, and recovered expression of AKT inactivation, which revealed the important role of ROS in apoptosis and AKT regulation. In vivo, combination therapy showed the strongest anti-tumor effects compared with single agents, without obvious additional toxicity. These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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.

Combination of Rapamycin and Resveratrol for Treatment of Bladder Cancer.

PubMed

Alayev, Anya; Salamon, Rachel S; Schwartz, Naomi S; Berman, Adi Y; Wiener, Sara L; Holz, Marina K

2017-02-01

Loss of TSC1 function, a crucial negative regulator of mTOR signaling, is a common alteration in bladder cancer. Mutations in other members of the PI3K pathway, leading to mTOR activation, are also found in bladder cancer. This provides rationale for targeting mTOR for treatment of bladder cancer characterized by TSC1 mutations and/or mTOR activation. In this study, we asked whether combination treatment with rapamycin and resveratrol could be effective in concurrently inhibiting mTOR and PI3K signaling and inducing cell death in bladder cancer cells. In combination with rapamycin, resveratrol was able to block rapamycin-induced Akt activation, while maintaining mTOR pathway inhibition. In addition, combination treatment with rapamycin and resveratrol induced cell death specifically in TSC1 -/- MEF cells, and not in wild-type MEFs. Similarly, resveratrol alone or in combination with rapamycin induced cell death in human bladder cancer cell lines. These data indicate that administration of resveratrol together with rapamycin may be a promising therapeutic option for treatment of bladder cancer. J. Cell. Physiol. 232: 436-446, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Kelp waste extracts combined with acetate enhances the biofuel characteristics of Chlorella sorokiniana.

PubMed

Zheng, Shiyan; He, Meilin; Sui, Yangsui; Gebreluel, Temesgen; Zou, Shanmei; Kemuma, Nyabuto Dorothy; Wang, Changhai

2017-02-01

To probe the effect of kelp waste extracts (KWE) combined with acetate on biochemical composition of Chlorella sorokiniana, the cultures were performed under independent/combined treatment of KWE and acetate. The results showed that high cell density and biomass were obtained by KWE combined with acetate treatments, whose biomass productivity increased by 79.69-102.57% and 20.04-35.32% compared with 3.0gL -1 acetate and KWE treatments respectively. The maximal neutral lipid per cell and lipid productivity were gained in KWE combined with 3.0gL -1 acetate treatment, which increased by 16.32% and 129.03% compared with 3.0gL -1 acetate, and 253.35% and 70.74% compared with KWE treatment. Meanwhile, C18:3n3 and C18:2n6c contents were reduced to 4.90% and 11.88%, whereas C16:0 and C18:1n9c were improved to 28.71% and 37.76%. Hence, supplementing appropriate acetate in KWE cultures is supposed to be a great potential method for large-scale cultivation of C. sorokiniana to generate biofuel. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

PubMed

Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

2017-08-15

We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall efficacy of cancer immunotherapy.

Combined treatment with Ad-hTRAIL and DTIC or SAHA is associated with increased mitochondrial-mediated apoptosis in human melanoma cell lines.

PubMed

Lillehammer, Trine; Engesaeter, Birgit O; Prasmickaite, Lina; Maelandsmo, Gunhild M; Fodstad, Oystein; Engebraaten, Olav

2007-06-01

Currently, dacarbazine (DTIC) is the only approved systemic treatment for metastatic malignant melanoma. However, the modest treatment effect encourages studies on novel therapeutic molecules, delivery systems and combination therapies. Full-length TRAIL, delivered from an adenoviral vector (Ad-hTRAIL), was studied in combination with DTIC or the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in human melanoma cell lines. The cytotoxic potential of the combination treatments was assessed by cell viability measurements and CalcuSyn analysis. Involvement of apoptosis was analyzed by TUNEL staining, mitochondrial membrane potential measurements, and activation and expression levels of caspases and other mediators of apoptosis. Ad-hTRAIL in combination with DTIC or SAHA resulted in additive or synergistic growth inhibition compared to each treatment used as single agent. Both combinations augmented apoptosis, which was mediated through the death receptor (DR) pathway by enhanced activation of caspase-8, and through increased loss of mitochondrial integrity. Provoked cleavage of Bid, which bridges the extrinsic and intrinsic apoptosis pathways, and downregulation of the anti-apoptotic mediators Bcl-X(L), Mcl-1 and XIAP (but not Bcl-2) were critical contributing factors. Increased levels of DR4 and DR5 were not a common underlying mechanism as DTIC did not affect the levels of either of the receptors. However, SAHA-induced expression of DR4 may have reduced the TRAIL resistance in the SKMEL-28 cell line. Administration of Ad-hTRAIL in combination with DTIC or SAHA enhances apoptosis in human melanoma cell lines, and suggests that the therapeutic potential of such treatment strategies should be further evaluated for possible clinical use.

HIFU and Chemotherapy Synergistic Inhibitory Effect on Dunning AT2 Tumour-Bearing Rats

NASA Astrophysics Data System (ADS)

Curiel, Laura; Paparel, Philipe; Chesnais, Sabrina; Gelet, Albert; Chapelon, Jean-Yves

2005-03-01

Since there is no 100% satisfactory treatment for localized prostate cancer in patients presenting symptoms representing a poor prognosis (stage T3, high Gleason score, PSA level greater than 15 ng/ml, etc.), this study aimed to evaluate the therapeutic and synergistic inhibition effects of using High Intensity Focused Ultrasound (HIFU) in combination with chemotherapy (Taxane + Estramustine). Forty-one Dunning AT2 tumour-bearing Copenhagen rats receiving HIFU and/or chemotherapy were divided into four groups: control group; chemotherapy group; HIFU group; and HIFU-chemotherapy combined group. Increase in the tumour volume was observed over 3 weeks and the tumour volume doubling time was evaluated. Growth curves for each group were then plotted and statistically evaluated. HIFU treatment combined with Taxane + Estramusine was found to have a significant synergistic effect; on day 30, the distribution of tumour volume relative to the treatment group was significantly different (p = 0.0007). The control group volumes were significantly greater than those of the chemotherapy-only (p = 0.006) or HIFU-only group (p = 0.006). The greatest difference was observed between the chemotherapy plus HIFU combined group and the control group. Additionally, tumour-doubling times were 7.7 days for the control group, 13.2 days for the HIFU-only group, and 31.2 days for the chemotherapy plus HIFU group. The differences in tumour growth rates between the chemotherapy plus HIFU combined group and a chemotherapy-only + HIFU-only grouping was 3.8% (p = 0.0020). Thus, the combined chemotherapy plus HIFU treatment was clearly more effective in reducing the tumour size than HIFU only or chemotherapy only, which indicates a synergy between the two types of treatment. Our results suggest that this combined therapy could be useful for the treatment of high-risk prostate cancer.

Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor alpha combination treatment of EL4-lymphoma-bearing C57BL/6 mice.

PubMed

Krawczyk, C M; Verstovsek, S; Ujházy, P; Maccubbin, D; Ehrke, M J

1995-06-01

A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor alpha (TNF alpha, 1000 units injection) on days 13, 16, 18, 21, and 23, resulted in about 60% long-term survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNF alpha was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNF alpha. These results indicate that treatment with a single moderate dose of CY in combination with TNF alpha is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

Pharmacological treatment optimization for stable chronic obstructive pulmonary disease. Proposals from the Société de Pneumologie de Langue Française.

PubMed

Zysman, M; Chabot, F; Devillier, P; Housset, B; Morelot-Panzini, C; Roche, N

2016-12-01

The Société de Pneumologie de Langue Française proposes a decision algorithm on long-term pharmacological COPD treatment. A working group reviewed the literature published between January 2009 and May 2016. This document lays out proposals and not guidelines. It only focuses on pharmacological treatments except vaccinations, smoking cessation treatments and oxygen therapy. Any COPD diagnosis, based on pulmonary function tests, should lead to recommend smoking cessation, vaccinations, physical activity, pulmonary rehabilitation in case of activity limitation, and short-acting bronchodilators. Symptoms like dyspnea and exacerbations determine the therapeutic choices. In case of daily dyspnea and/or exacerbations, a long-acting bronchodilator should be suggested (beta-2 agonist, LABA or anticholinergics, LAMA). A clinical and lung function reevaluation is suggested 1 to 3 months after any treatment modification and every 3-12 months according to the severity of the disease. In case of persisting dyspnea, a fixed dose LABA+LAMA combination improves pulmonary function (FEV1), quality of life, dyspnea and decreases exacerbations without increasing side effects. In case of frequent exacerbations and a FEV1≤70%, a fixed dose long-acting bronchodilator combination or a LABA+ inhaled corticosteroids (ICS) combination can be proposed. A triple combination (LABA+LAMA+ICS) is indicated when exacerbations persist despite one of these combinations. Dyspnea in spite of a bronchodilator combination or exacerbations in spite of a triple combination should lead to consider other pharmacological treatments (theophylline if dyspnea, macrolides if exacerbations, low-dose opioids if refractory dyspnea). Copyright © 2016. Published by Elsevier Masson SAS.

Combination strategy targeting VEGF and HGF/c-met in human renal cell carcinoma models.

PubMed

Ciamporcero, Eric; Miles, Kiersten Marie; Adelaiye, Remi; Ramakrishnan, Swathi; Shen, Li; Ku, ShengYu; Pizzimenti, Stefania; Sennino, Barbara; Barrera, Giuseppina; Pili, Roberto

2015-01-01

Alternative pathways to the VEGF, such as hepatocyte growth factor or HGF/c-met, are emerging as key players in tumor angiogenesis and resistance to anti-VEGF therapies. The aim of this study was to assess the effects of a combination strategy targeting the VEGF and c-met pathways in clear cell renal cell carcinoma (ccRCC) models. Male SCID mice (8/group) were implanted with 786-O tumor pieces and treated with either a selective VEGF receptor tyrosine kinase inhibitor, axitinib (36 mg/kg, 2×/day); a c-met inhibitor, crizotinib (25 mg/kg, 1×/day); or combination. We further tested this drug combination in a human ccRCC patient-derived xenograft, RP-R-01, in both VEGF-targeted therapy-sensitive and -resistant models. To evaluate the resistant phenotype, we established an RP-R-01 sunitinib-resistant model by continuous sunitinib treatment (60 mg/kg, 1×/day) of RP-R-01-bearing mice. Treatment with single-agent crizotinib reduced tumor vascularization but failed to inhibit tumor growth in either model, despite also a significant increase of c-met expression and phosphorylation in the sunitinib-resistant tumors. In contrast, axitinib treatment was effective in inhibiting angiogenesis and tumor growth in both models, with its antitumor effect significantly increased by the combined treatment with crizotinib, independently from c-met expression. Combination treatment also induced prolonged survival and significant tumor growth inhibition in the 786-O human RCC model. Overall, our results support the rationale for the clinical testing of combined VEGF and HGF/c-met pathway blockade in the treatment of ccRCC, both in first- and second-line setting. ©2014 American Association for Cancer Research.

Effects of topical combinations of clonidine and pentoxifylline on capsaicin-induced allodynia and postcapsaicin tourniquet-induced pain in healthy volunteers: a double-blind, randomized, controlled study.

PubMed

Ragavendran, J Vaigunda; Laferrière, André; Bennett, Gary J; Ware, Mark A; Gandhi, Wiebke; Bley, Keith; Schweinhardt, Petra; Coderre, Terence J

2016-10-01

This double-blind randomized controlled study was designed to evaluate the analgesic effects of topical treatments with clonidine (CLON) and pentoxifylline (PTX) tested alone or as low- and high-dose combinations in a human experimental model of pain. Of 69 healthy subjects aged 18 to 60 years, 23 each were randomly allocated to low-dose (0.04% + 2%) and high-dose (0.1% + 5%) CLON + PTX groups. Both of these groups also received their corresponding placebos in one of 2 treatment periods separated by at least 48 hours. Twenty-three additional subjects received either CLON (0.1%) or PTX (5%) as single drug treatments, in each of 2 treatment periods. Assessment of analgesic efficacy was based on allodynic effects of previous intraepidermal capsaicin injection, as well as postcapsaicin tourniquet-induced pain 50 minutes following capsaicin injection. Visual Analogue Scale (VAS) ratings of pain intensity and the area of dynamic mechanical allodynia were the primary outcome measures, whereas area of punctate mechanical allodynia (PMA) served as a secondary outcome measure. Topical treatments with high- or low-dose combinations significantly reduced VAS ratings compared with corresponding placebo treatments throughout the period of postcapsaicin tourniquet-induced pain. Importantly, the high-dose combination produced lower VAS ratings than CLON alone, which were lower than PTX alone. Results also revealed significant inhibition of postcapsaicin dynamic mechanical allodynia and PMA for the high-dose combination compared with placebo, and of PMA for CLON compared with the low-dose combination. Hence, the present data are supportive of further clinical investigation of the high-dose topical combination of CLON + PTX in complex regional pain syndrome and neuropathic pain patients, for which our preclinical data predict efficacy.

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

PubMed

Patel, Pinaki B; Thakkar, Vasudev R

2015-03-01

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

Subacute combined degeneration of the cord due to folate deficiency: response to methyl folate treatment.

PubMed Central

Lever, E G; Elwes, R D; Williams, A; Reynolds, E H

1986-01-01

Subacute combined degeneration of the cord is a rare complication of folate deficiency. Disturbance of methylation reactions in nervous tissue probably underlie subacute combined degeneration of the cord arising from folate as well as vitamin B12 deficiency. Methyl tetrahydrofolate is the form in which folic acid is transported into the CNS. Therefore methyl tetrahydrofolate treatment of the neurological and psychiatric manifestations of folate deficiency would seem to be theoretically advantageous. A case of subacute combined degeneration of the cord due to dietary folate deficiency and associated with an organic brain syndrome is reported. There was striking haematological, neurological and psychiatric response to methyl folate treatment. PMID:3783183

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.

Synergetic effects of ultrasound and slightly acidic electrolyzed water against Staphylococcus aureus evaluated by flow cytometry and electron microscopy.

PubMed

Li, Jiao; Ding, Tian; Liao, Xinyu; Chen, Shiguo; Ye, Xingqian; Liu, Donghong

2017-09-01

This study evaluated the synergetic effects of ultrasound and slightly acidic electrolyzed water (SAEW) on the inactivation of Staphylococcus aureus using flow cytometry and electron microscopy. The individual ultrasound treatment for 10min only resulted in 0.36logCFU/mL reductions of S. aureus, while the SAEW treatment alone for 10min resulted in 3.06logCFU/mL reductions. The log reductions caused by combined treatment were enhanced to 3.68logCFU/mL, which were greater than the sum of individual treatments. This phenomenon was referred to as synergistic effects. FCM analysis distinguished live and dead cells as well as revealed dynamic changes in the physiological states of S. aureus after different treatments. The combined treatment greatly reduced the number of viable but nonculturable (VBNC) bacteria to 0.07%; in contrast, a single ultrasound treatment for 10min induced the formation of VBNC cells to 45.75%. Scanning and transmission electron microscopy analysis revealed that greater damage to the appearance and ultrastructure of S. aureus were achieved after combined ultrasound-SAEW treatment compared to either treatment alone. These results indicated that combining ultrasound with SAEW is a promising sterilization technology with potential uses for environmental remediation and food preservation. Copyright © 2016 Elsevier B.V. All rights reserved.

Combination of selenium-enriched green tea polysaccharides and Huo-ji polysaccharides synergistically enhances antioxidant and immune activity in mice.

PubMed

Yuan, Chengfu; Li, Zhihong; Peng, Fan; Xiao, Fangxiang; Ren, Dongming; Xue, Hui; Chen, Tao; Mushtaq, Gohar; Kamal, Mohammad Amjad

2015-12-01

The aim of this study was to investigate the influence of a combination of selenium-enriched green tea polysaccharides (Se-GTP) and Huo-ji polysaccharides (HJP) on the immune function and antioxidant activity in mice. The results showed that the indices of spleen and thymus were markedly increased, and the activity of natural killer (NK) cell was promoted in mice treated with the combination of Se-GTP and HJP. The combined treatment of Se-GTP and HJP also reduced the content of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in splenocytes. In addition, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were remarkably enhanced, and malondialdehyde (MDA) levels were significantly reduced in mice treated with combination of Se-GTP and HJP. Furthermore, the combined treatment of Se-GTP and HJP increased nuclear factor erythroid 2-related factor (Nrf2) expression at mRNA and protein levels in splenocytes. The effects of the combination treatment of Se-GTP and HJP in mice were stronger than with Se-GTP or HJP treatment alone. Our study suggests that the combined administration of Se-GTP and HJP can synergistically improve immune function and decrease the oxidative stress by enhancing the mechanisms involved in the clearance of free radicals. © 2015 Society of Chemical Industry.

Effect of preventive (beta blocker) treatment, behavioural migraine management, or their combination on outcomes of optimised acute treatment in frequent migraine: randomised controlled trial.

PubMed

Holroyd, Kenneth A; Cottrell, Constance K; O'Donnell, Francis J; Cordingley, Gary E; Drew, Jana B; Carlson, Bruce W; Himawan, Lina

2010-09-29

To determine if the addition of preventive drug treatment (β blocker), brief behavioural migraine management, or their combination improves the outcome of optimised acute treatment in the management of frequent migraine. Randomised placebo controlled trial over 16 months from July 2001 to November 2005. Two outpatient sites in Ohio, USA. 232 adults (mean age 38 years; 79% female) with diagnosis of migraine with or without aura according to International Headache Society classification of headache disorders criteria, who recorded at least three migraines with disability per 30 days (mean 5.5 migraines/30 days), during an optimised run-in of acute treatment. Addition of one of four preventive treatments to optimised acute treatment: β blocker (n=53), matched placebo (n=55), behavioural migraine management plus placebo (n=55), or behavioural migraine management plus β blocker (n=69). The primary outcome was change in migraines/30 days; secondary outcomes included change in migraine days/30 days and change in migraine specific quality of life scores. Mixed model analysis showed statistically significant (P≤0.05) differences in outcomes among the four added treatments for both the primary outcome (migraines/30 days) and the two secondary outcomes (change in migraine days/30 days and change in migraine specific quality of life scores). The addition of combined β blocker and behavioural migraine management (-3.3 migraines/30 days, 95% confidence interval -3.2 to -3.5), but not the addition of β blocker alone (-2.1 migraines/30 days, -1.9 to -2.2) or behavioural migraine management alone (-2.2 migraines migraines/30 days, -2.0 to -2.4), improved outcomes compared with optimised acute treatment alone (-2.1 migraines/30 days, -1.9 to -2.2). For a clinically significant (≥50% reduction) in migraines/30 days, the number needed to treat for optimised acute treatment plus combined β blocker and behavioural migraine management was 3.1 compared with optimised acute treatment alone, 2.6 compared with optimised acute treatment plus β blocker, and 3.1 compared with optimised acute treatment plus behavioural migraine management. Results were consistent for the two secondary outcomes, and at both month 10 (the primary endpoint) and month 16. The addition of combined β blocker plus behavioural migraine management, but not the addition of β blocker alone or behavioural migraine management alone, improved outcomes of optimised acute treatment. Combined β blocker treatment and behavioural migraine management may improve outcomes in the treatment of frequent migraine. Clinical trials NCT00910689.

[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.

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2015-03-01

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

A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias.

PubMed

Goldberg, Henrique; Mibielli, Marco Antonio; Nunes, Carlos Pereira; Goldberg, Stephanie Wrobel; Buchman, Luiz; Mezitis, Spyros Ge; Rzetelna, Helio; Oliveira, Lisa; Geller, Mauro; Wajnsztajn, Fernanda

2017-01-01

This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B 12 . To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B 12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B 12 . A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B 12, and Group B (n=200) receiving vitamin B 12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B 12 , with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. The combination of uridine, cytidine, and vitamin B 12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma.

Combined effects of Lanthanum(III) and elevated Ultraviolet-B radiation on root nitrogen nutrient in soybean seedlings.

PubMed

Huang, Guangrong; Wang, Lihong; Sun, Zhaoguo; Li, Xiaodong; Zhou, Qing; Huang, Xiaohua

2015-02-01

Rare earth element pollution and elevated ultraviolet-B (UV-B) radiation occur simultaneously in some regions, but the combined effects of these two factors on plants have not attracted enough attention. Nitrogen nutrient is vital to plant growth. In this study, the combined effects of lanthanum(III) and elevated UV-B radiation on nitrate reduction and ammonia assimilation in soybean (Glycine max L.) roots were investigated. Treatment with 0.08 mmol L(-1) La(III) did not change the effects of elevated UV-B radiation on nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), glutamate synthase (GOGAT), glutamate dehydrogenase (GDH), nitrate, ammonium, amino acids, or soluble protein in the roots. Treatment with 0.24 mmol L(-1) La(III) and elevated UV-B radiation synergistically decreased the NR, NiR, GS, and GOGAT activities as well as the nitrate, amino acid, and soluble protein levels, except for the GDH activity and ammonium content. Combined treatment with 1.20 mmol L(-1) La(III) and elevated UV-B radiation produced severely deleterious effects on all test indices, and these effects were stronger than those induced by La(III) or elevated UV-B radiation treatment alone. Following the withdrawal of La(III) and elevated UV-B radiation, all test indices for the combined treatments with 0.08/0.24 mmol L(-1) La(III) and elevated UV-B radiation recovered to a certain extent, but they could not recover for treatments with 1.20 mmol L(-1) La(III) and elevated UV-B radiation. In summary, combined treatment with La(III) and elevated UV-B radiation seriously affected nitrogen nutrition in soybean roots through the inhibition of nitrate reduction and ammonia assimilation.

Effect of using a combination of lid wipes, eye drops, and omega-3 supplements on meibomian gland functionality in patients with lipid deficient/evaporative dry eye.

PubMed

Korb, Donald R; Blackie, Caroline A; Finnemore, Victor M; Douglass, Teresa

2015-04-01

The aim of this study was to assess the efficacy of using a combination treatment approach consisting of lipid emulsion eye drops, eyelid cleansing wipes, and omega-3 vitamin supplements compared with warm compresses in improving meibomian gland functionality in patients with lipid-deficient/evaporative dry eye disease (LDDE). This single-center, open-label, investigator-masked, randomized study enrolled patients aged ≥18 years, clinically diagnosed with LDDE defined as having ≤6 functional meibomian glands [meibomian gland yielding liquid secretion (MGYLS)] and positive for dry eye symptoms at screening. Patients were randomized to receive either the combination treatment (lipid emulsion eye drops, omega-3 supplements, and lid hygiene with eyelid wipes) or to apply warm, wet compresses once daily, 8 minutes per day, for 3 months. Meibomian gland functionality (number of MGYLS; primary outcome) and patient-reported subjective assessments (SPEED and OSDI questionnaires; secondary outcomes) were evaluated. Adverse events (AEs) and visual acuity were assessed as safety endpoints. Mean patient age was 41.7 years (n = 26; n = 13 per group). Mean ± SD number of MGYLS was not statistically significantly different between groups at baseline (combination treatment, 3.5 ± 1.5; warm compresses, 4.2 ± 1.4, P > 0.5), and was significantly greater with combination treatment versus warm compresses after 3 months of treatment (9.3 ± 2.7 vs. 4.7 ± 2.3; P = 0.006). Dry eye symptoms were significantly improved in both groups at all follow-up visits. Two AEs unrelated to treatment were reported; the BCVA was unchanged from baseline in both groups. The combination treatment regimen resulted in significant improvement in meibomian gland functionality and dry eye symptoms. No safety issues were observed.

Combined local and systemic bleomycin administration in electrochemotherapy to reduce the number of treatment sessions

PubMed Central

Tellado, Matias; Olaiz, Nahuel; Michinski, Sebastian; Marshall, Guillermo

2016-01-01

Background Electrochemotherapy (ECT), a medical treatment widely used in human patients for tumor treatment, increases bleomycin toxicity by 1000 fold in the treated area with an objective response rate of around 80%. Despite its high response rate, there are still 20% of cases in which the patients are not responding. This could be ascribed to the fact that bleomycin, when administered systemically, is not reaching the whole tumor mass properly because of the characteristics of tumor vascularization, in which case local administration could cover areas that are unreachable by systemic administration. Patients and methods We propose combined bleomycin administration, both systemic and local, using companion animals as models. We selected 22 canine patients which failed to achieve a complete response after an ECT treatment session. Eleven underwent another standard ECT session (control group), while 11 received a combined local and systemic administration of bleomycin in the second treatment session. Results According to the WHO criteria, the response rates in the combined administration group were: complete response (CR) 54% (6), partial response (PR) 36% (4), stable disease (SD) 10% (1). In the control group, these were: CR 0% (0), PR 19% (2), SD 63% (7), progressive disease (PD) 18% (2). In the combined group 91% objective responses (CR+PR) were obtained. In the control group 19% objective responses were obtained. The difference in the response rate between the treatment groups was significant (p < 0.01). Conclusions Combined local and systemic bleomycin administration was effective in previously to ECT non responding canine patients. The results indicate that this approach could be useful and effective in specific population of patients and reduce the number of treatment sessions needed to obtain an objective response. PMID:27069450

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine.

PubMed

Swalve, Natashia; Smethells, John R; Zlebnik, Natalie E; Carroll, Marilyn E

2016-06-01

Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e., relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-primed reinstatement of cocaine-seeking. Adult male and female Wistar rats lever-pressed under a FR 1 schedule for cocaine infusions (0.4mg/kg/inf). After 14 sessions of stable responding in daily 2-h sessions, rats underwent a 21-day extinction period when no drug or drug-related stimuli were present. Rats were then separated into four groups that received PRO (0.5mg/kg) alone (PRO+SAL), ATO (1.5mg/kg) alone (VEH+ATO), control (VEH+SAL) or combination (PRO+ATO) treatments prior to the reinstatement condition. Reinstatement of cocaine-seeking to cues and/or drug injections of cocaine or caffeine was tested after extinction. During maintenance, females self-administered more cocaine than males, but no sex differences were seen during extinction. Females showed greater cocaine-seeking than males after a CAF priming injection. Individual treatment with ATO did not decrease reinstatement under any priming condition; however, the combination treatment decreased cocaine-seeking under the COC+CUES priming condition in males, and both PRO alone and the combination treatment decreased cocaine-seeking in the CAF+CUES condition in females. Overall, PRO alone was only effective in reducing reinstatement in females, while the combination treatment was consistently effective in reducing reinstatement in both sexes. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of Electrocautery Needle Knife Combined with Balloon Dilatation versus Balloon Dilatation in the Treatment of Tracheal Fibrotic Scar Stenosis.

PubMed

Bo, Liyan; Li, Congcong; Chen, Min; Mu, Deguang; Jin, Faguang

Electrocautery needle knives can largely reduce scar and granulation tissue hyperplasia and play an important role in treating patients with benign stricture. The aim of this retrospective study was to evaluate the efficacy and safety of electrocautery needle knife combined with balloon dilatation versus balloon dilatation alone in the treatment of tracheal stenosis caused by tracheal intubation or tracheotomy. We retrospectively analysed the clinical data of 43 patients with tracheal stenosis caused by tracheotomy or tracheal intubation in our department from January 2013 to January 2016. Among these 43 patients, 23 had simple web-like stenosis and 20 had complex steno sis. All patients were treated under general anaesthesia, and the treatment methods were (1) balloon dilatation alone, (2) needle knife excision of fibrotic tissue combined with balloon dilatation, and (3) needle knife radial incision of fibrotic tissue combined with balloon dilatation. After treatment the symptoms, such as shortness of breath, were markedly improved immediately in all cases. The stenosis degree of patients who were treated with the elec-trocautery needle knife combined with balloon dilatation had better improvement compared with that of those treated with balloon dilatation treatment alone after 3 months (0.45 ± 0.04 vs. 0.67 ± 0.05, p < 0.01), and the proportion of restenosis occurrence that required further treatment was decreased at 6 months (46.9 vs. 81.8%), especially for the web-like stenosis patients, as most of their stenoses dilated with no obvious restenosis and achieved clinical cure. Electrocautery needle knife combined with balloon dilatation is an effective and safe treatment for tracheal fibrotic stenosis compared with balloon dilatation alone. © 2017 S. Karger AG, Basel.

Efficacy of Combined Therapy with Liposome-Encapsulated Meglumine Antimoniate and Allopurinol in Treatment of Canine Visceral Leishmaniasis

PubMed Central

da Silva, Sydnei M.; Amorim, Izabela F. G.; Ribeiro, Raul R.; Azevedo, Erly G.; Demicheli, Cynthia; Melo, Maria N.; Tafuri, Wagner L.; Gontijo, Nelder F.; Michalick, Marilene S. M.

2012-01-01

An innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months after treatment, parasites were still found in the bone marrow of all treated dogs. In order to improve treatment with LMA, the present study aimed to evaluate its efficacy in combination with allopurinol. Mongrel dogs naturally infected with Leishmania infantum were treated with six doses of LMA (6.5 mg Sb/kg of body weight/dose) given at 4-day intervals, plus allopurinol (20 mg/kg/24 h per os) for 140 days. Comparison was made with groups treated with LMA, allopurinol, empty liposomes plus allopurinol, empty liposomes, and saline. Dogs remained without treatment from day 140 to 200 after the start of treatment. The drug combination promoted both clinical improvement of dogs and significant reduction in the parasitic load in bone marrow and spleen on days 140 and 200 compared to these parameters in the pretreatment period. This is in contrast with the other protocols, which did not result in significant reduction of the bone marrow parasite load on day 200. Strikingly, the combined treatment, in contrast to the other regimens, induced negative quantitative PCR (qPCR) results in the liver of 100% of the dogs. Both xenodiagnosis and skin parasite determination by qPCR indicated that the drug combination was effective in blocking the transmission of skin parasites to sand flies. Based on all of the parasitological tests performed on day 200, 50% of the animals that received the combined treatment were considered cured. PMID:22411610

“This is Not Who I Want to be:” Experiences of Opioid-Dependent Youth Before, and During, Combined Buprenorphine and Behavioral Treatment

PubMed Central

Moore, Sarah K.; Guarino, Honoria; Marsch, Lisa A.

2018-01-01

Novel, qualitative data were collected from youth in treatment for opioid dependence (2009–2010) regarding their experiences with opioid dependence and combined behavioral–pharmacological treatment. Urban youth participants were recruited from a larger randomized controlled trial examining the relative efficacy of two tapers of buprenorphine–naloxone, combined with behavioral treatment (ages 13–24 eligible). Twenty-two youth participated in 1- to 1.5-hour semi-structured interviews. A grounded theory approach guided the analysis. The results have the potential to inform the development of efficacious treatments for this growing, yet understudied, group of youth. Study implications and limitations are noted, and future research is prescribed. (NIDA #1R01 DA018297). PMID:24041131

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells

PubMed Central

Hsieh, Chih-Hsiung; Lu, Chueh-Hsuan; Chen, Wei-Ting; Ma, Bo-Lun

2017-01-01

Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy. PMID:29186186

Application of non-invasive low strength pulsed electric field to EGCG treatment synergistically enhanced the inhibition effect on PANC-1 cells.

PubMed

Hsieh, Chih-Hsiung; Lu, Chueh-Hsuan; Chen, Wei-Ting; Ma, Bo-Lun; Chao, Chih-Yu

2017-01-01

Traditional therapies for pancreatic cancer are usually expensive and likely to cause side effects, and most patients have the risk of recurrence and suffering pain. Here, we investigated combination treatment of epigallocatechin-3-gallate (EGCG) and non-invasive low strength pulsed electric field (PEF) on the human pancreatic cell line PANC-1. Cells were cultured in various concentrations of EGCG and exposed to trains of PEF. The results showed that the low strength PEF alone or single treatment with low concentration of EGCG did not obviously affect the cell proliferation and migration in PANC-1. However, the EGCG-induced inhibitions of cell viability and migration ability in PANC-1 were dramatically enhanced by the further exposure of low strength PEF (60 V/cm). In particular, the same combination treatment caused less inhibition of cell viability in non-malignant HEK293 cells. We also found the combination treatment significantly decreased the ratio of Bcl-2/Bax protein and increased caspase activity in PANC-1 cells, resulting in the promotion of apoptotic responses, evidenced by chromatin condensation. The findings of the present study reveal the synergistic reactions in the combination treatment may severely disturb mitochondria, enhance the intrinsic pathway transduction, and effectively induce apoptosis; moreover, the migration and invasion of PANC-1 cancer cells were also significantly suppressed. Since normal cells are less sensitive to this combination treatment, and the non-invasive PEF could be modified to focus on a specific location, this treatment may serve as a promising method for anti-cancer therapy.

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.

Comparison of the clinical outcomes between antiviral-naïve patients treated with entecavir and lamivudine-resistant patients receiving adefovir add-on lamivudine combination treatment

PubMed Central

Kim, Hong Joo; Park, Soo Kyung; Yang, Hyo Joon; Jung, Yoon Suk; Park, Jung Ho; Park, Dong Il; Cho, Yong Kyun; Sohn, Chong Il; Jeon, Woo Kyu; Kim, Byung Ik; Choi, Kyu Yong

2016-01-01

Background/Aims To analyze the effects of preexisting lamivudine (LAM) resistance and applying antiviral treatment (adefovir [ADV] add-on LAM combination treatment) on long-term treatment outcomes, and comparing the clinical outcomes of antiviral-naïve chronic hepatitis B patients receiving entecavir (ETV) monotherapy. Methods This study enrolled 73 antiviral-naïve patients who received 0.5-mg ETV as an initial therapy and 54 patients who received ADV add-on LAM combination treatment as a rescue therapy from July 2006 to July 2010. Results During 24-month treatments, the decreases in serum log10HBV-DNA values (copies/mL) were significantly greater in the antiviral-naïve patients treated with ETV than the patients receiving ADV add-on LAM combination treatment. The biochemical response rates for alanine aminotransferase normalization at 6 months (ETV) and 12 months (ADV add-on LAM) were 90.4% (66/73) and 77.8% (42/54), respectively (P=0.048). A Kaplan-Meier analysis indicated that the rates of serologic response, viral breakthrough, and emergence of genotypic resistance did not differ significantly between the two patient groups. There were also no significant intergroup differences in the rates of disease progression (PD) and new development of hepatocellular carcinoma (HCC). Conclusion The long-term clinical outcomes of antiviral-naïve patients treated with ETV and LAM-resistant patients receiving ADV add-on LAM combination treatment were comparable in terms of the emergence of HCC and disease progression. PMID:27729626

Combined immunotherapy and antiangiogenic therapy of cancer with microencapsulated cells.

PubMed

Cirone, Pasquale; Bourgeois, Jacqueline M; Shen, Feng; Chang, Patricia L

2004-10-01

An alternative form of gene therapy involves immunoisolation of a nonautologous cell line engineered to secrete a therapeutic product. Encapsulation of these cells in a biocompatible polymer serves to protect these allogeneic cells from host-versus-graft rejection while recombinant products and nutrients are able to pass by diffusion. This strategy was applied to the treatment of cancer with some success by delivering either interleukin 2 or angiostatin. However, as cancer is a complex, multifactorial disease, a multipronged approach is now being developed to attack tumorigenesis via multiple pathways in order to improve treatment efficacy. A combination of immunotherapy with angiostatic therapy was investigated by treating B16-F0/neu melanoma-bearing mice with intraperitoneally implanted, microencapsulated mouse myoblasts (C2C12) genetically modified to deliver angiostatin and an interleukin 2 fusion protein (sFvIL-2). The combination treatment resulted in improved survival, delayed tumor growth, and increased histological indices of antitumor activity (apoptosis and necrosis). In addition to improved efficacy, the combination treatment also ameliorated some of the undesirable side effects from the individual treatments that have led to the previous failure of the single treatments, for example, inflammatory response to IL-2 or vascular mimicry due to angiostatin. In conclusion, the combination of immuno- and antiangiogenic therapies delivered by immunoisolated cells was superior to individual treatments for antitumorigenesis activity, not only because of their known mechanisms of action but also because of unexpected protection against the adverse side effects of the single treatments. Thus, the concept of a "cocktail" strategy, with microencapsulation delivering multiple antitumor recombinant molecules to improve efficacy, is validated.

Combining Lactic Acid Spray with Near-Infrared Radiation Heating To Inactivate Salmonella enterica Serovar Enteritidis on Almond and Pine Nut Kernels

PubMed Central

Ha, Jae-Won

2015-01-01

The aim of this study was to investigate the efficacy of near-infrared radiation (NIR) heating combined with lactic acid (LA) sprays for inactivating Salmonella enterica serovar Enteritidis on almond and pine nut kernels and to elucidate the mechanisms of the lethal effect of the NIR-LA combined treatment. Also, the effect of the combination treatment on product quality was determined. Separately prepared S. Enteritidis phage type (PT) 30 and non-PT 30 S. Enteritidis cocktails were inoculated onto almond and pine nut kernels, respectively, followed by treatments with NIR or 2% LA spray alone, NIR with distilled water spray (NIR-DW), and NIR with 2% LA spray (NIR-LA). Although surface temperatures of nuts treated with NIR were higher than those subjected to NIR-DW or NIR-LA treatment, more S. Enteritidis survived after NIR treatment alone. The effectiveness of NIR-DW and NIR-LA was similar, but significantly more sublethally injured cells were recovered from NIR-DW-treated samples. We confirmed that the enhanced bactericidal effect of the NIR-LA combination may not be attributable to cell membrane damage per se. NIR heat treatment might allow S. Enteritidis cells to become permeable to applied LA solution. The NIR-LA treatment (5 min) did not significantly (P > 0.05) cause changes in the lipid peroxidation parameters, total phenolic contents, color values, moisture contents, and sensory attributes of nut kernels. Given the results of the present study, NIR-LA treatment may be a potential intervention for controlling food-borne pathogens on nut kernel products. PMID:25911473

Alendronate (ALN) combined with Osteoprotegerin (OPG) significantly improves mechanical properties of long bone than the single use of ALN or OPG in the ovariectomized rats

PubMed Central

2011-01-01

Background Alendronate (ALN) is the most common form of bisphosphonates used for the treatment of osteoporosis. Osteoprotegerin (OPG) has also been shown to reduce osteoporotic changes in both humans and experimental animals after systemic administration. The aim of this current study was to test if the anti-resorption effects of ALN may be enhanced when used in combination with OPG. Objectives To investigate the effects of ALN, OPG or combined on bone mass and bone mechanical properties in ovariectomized (OVX) rats. Methods OVX rats were treated with ALN, OPG-Fc, or OPG-Fc and ALN. Biochemical markers, trabecular bone mass, biomechanics, histomorphometry and RANKL expression in the bone tissues were examined following the treatments. Results The treatment of ALN, OPG-Fc and ALN+OPG-Fc all prevented bone loss in the OVX-rats, there was no statistical difference among the three treatment groups in terms of vertebrae BMD, mineralizing surfaces, mineral apposition rate, BFR/BS. The ALN+OPG-Fc treatment group had significantly increased the mechanical strength of lumber vertebral bodies and femoral shafts when compared to the ALN and OPG-Fc treatment groups. The RANKL protein expression in the vertebral bones was significantly decreased in the ALN and ALN+OPG-Fc treatment groups, suggesting the combined use of OPG-Fc and ALN might have amplified inhibition of bone resorption through inhibiting RANKL-dependent osteoclastogenesis. Conclusion The combined use of OPG-Fc and ALN may be a new treatment strategy for reversing bone loss and restoring bone quality in osteoprotic disorders. PMID:21752290

Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

PubMed

Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

2010-01-01

To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

Efficacy of manual and manipulative therapy in the perception of pain and cervical motion in patients with tension-type headache: a randomized, controlled clinical trial.

PubMed

Espí-López, Gemma V; Gómez-Conesa, Antonia

2014-03-01

The purpose of this study was to evaluate the efficacy of manipulative and manual therapy treatments with regard to pain perception and neck mobility in patients with tension-type headache. A randomized clinical trial was conducted on 84 adults diagnosed with tension-type headache. Eighty-four subjects were enrolled in this study: 68 women and 16 men. Mean age was 39.76 years, ranging from 18 to 65 years. A total of 57.1% were diagnosed with chronic tension-type headache and 42.9% with tension-type headache. Participants were divided into 3 treatment groups (manual therapy, manipulative therapy, a combination of manual and manipulative therapy) and a control group. Four treatment sessions were administered during 4 weeks, with posttreatment assessment and follow-up at 1 month. Cervical ranges of motion pain perception, and frequency and intensity of headaches were assessed. All 3 treatment groups showed significant improvements in the different dimensions of pain perception. Manual therapy and manipulative treatment improved some cervical ranges of motion. Headache frequency was reduced with manipulative treatment (P < .008). Combined treatment reported improvement after the treatment (P < .000) and at follow-up (P < .002). Pain intensity improved after the treatment and at follow-up with manipulative therapy (P < .01) and combined treatment (P < .01). Both treatments, administered both separately and combined together, showed efficacy for patients with tension-type headache with regard to pain perception. As for cervical ranges of motion, treatments produced greater effect when separately administered.

Toxic effects and antitumor response of gemcitabine in combination with piroxicam treatment in dogs with transitional cell carcinoma of the urinary bladder.

PubMed

Marconato, Laura; Zini, Eric; Lindner, Donna; Suslak-Brown, Lisa; Nelson, Victoria; Jeglum, Ann K

2011-04-15

To investigate whether combined treatment with gemcitabine and piroxicam in dogs with transitional cell carcinoma (TCC) of the urinary bladder is tolerated and provides an advantage in terms of survival time over previously reported treatments. Clinical trial. Animals-38 dogs with TCC of the urinary bladder. Dogs were treated with gemcitabine (800 mg/m(2), IV over 30 to 60 minutes, q 7 d) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h). Complete blood cell counts were monitored prior to each gemcitabine treatment. All toxic effects of gemcitabine in dogs were recorded. Primary tumors were ultrasonographically reevaluated after 4 gemcitabine treatments. Dogs received a median of 8 gemcitabine treatments (range, 1 to 38 treatments/dog). In response to treatment, 10 of 38 (26.3%) dogs had grade 1 gastrointestinal tract signs, 11 (28.9%) had grade 2, and 5 (13.2%) had grade 3. Grade 1 neutropenia developed in 6 (15.8%) dogs and grade 2 and 3 neutropenia in 2 (5.3%) dogs each. Thrombocytopenia was rare. All dogs had improvement of clinical signs of disease. Two dogs had a complete tumor response, 8 had a partial response, 19 had stable disease, and 8 had progressive disease. Median survival time with treatment was 230 days. Administration of gemcitabine in combination with piroxicam treatment failed to provide a longer overall survival time in dogs with TCC of the urinary bladder, compared with previously reported treatment strategies. However, this combination of chemotherapy did provide a new treatment alternative with fewer adverse effects.

Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder

PubMed Central

Hollon, Steven D.; DeRubeis, Robert J.; Fawcett, Jan; Amsterdam, Jay D.; Shelton, Richard C.; Zajecka, John; Young, Paula R.; Gallop, Robert

2015-01-01

IMPORTANCE Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. OBJECTIVE To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD). DESIGN, SETTING, AND PARTICIPANTS A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved. INTERVENTIONS Antidepressant medication with or without CT. MAIN OUTCOMES AND MEASURES Blind evaluations of recovery with a modified version of the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation. RESULTS Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451 = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06–1.68; number needed to treat [NNT], 10; 95% CI, 5–72). This effect was conditioned on interactions with severity (t451 = 1.97; P = .05; NNT, 5) and chronicity (χ2 = 7.46; P = .02; NNT, 6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54–3.57; NNT, 3; 95% CI, 2–5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451 = −2.04; P = .04; HR, 0.66; 95% CI, 0.45–0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P = .01). Patients who received combined treatment reported fewer serious adverse events than did patients who received ADMs alone (49 vs 71; P = .02), largely because they experienced less time in an MDD episode. CONCLUSIONS AND RELEVANCE Cognitive therapy combined with ADM treatment enhances the rates of recovery from MDD relative to ADMs alone, with the effect limited to patients with severe, nonchronic depression. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00057577 PMID:25142196

Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial.

PubMed

Hollon, Steven D; DeRubeis, Robert J; Fawcett, Jan; Amsterdam, Jay D; Shelton, Richard C; Zajecka, John; Young, Paula R; Gallop, Robert

2014-10-01

Antidepressant medication (ADM) is efficacious in the treatment of depression, but not all patients achieve remission and fewer still achieve recovery with ADM alone. To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD). A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved. Antidepressant medication with or without CT. Blind evaluations of recovery with a modified version of the 17-item Hamilton Rating Scale for Depression and the Longitudinal Interval Follow-up Evaluation. Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451 = 2.45; P = .01; hazard ratio [HR], 1.33; 95% CI, 1.06-1.68; number needed to treat [NNT], 10; 95% CI, 5-72). This effect was conditioned on interactions with severity (t451 = 1.97; P = .05; NNT, 5) and chronicity (χ2 = 7.46; P = .02; NNT, 6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n = 146; t145 = 3.96; P = .001; HR, 2.34; 95% CI, 1.54-3.57; NNT, 3; 95% CI, 2-5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451 = -2.04; P = .04; HR, 0.66; 95% CI, 0.45-0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P = .01). Patients who received combined treatment reported fewer serious adverse events than did patients who received ADMs alone (49 vs 71; P = .02), largely because they experienced less time in an MDD episode. Cognitive therapy combined with ADM treatment enhances the rates of recovery from MDD relative to ADMs alone, with the effect limited to patients with severe, nonchronic depression. clinicaltrials.gov Identifier: NCT00057577.

Relative Cost-Effectiveness of Treatments for Adolescent Depression: 36-Week Results from the TADS Randomized Trial

ERIC Educational Resources Information Center

Domino, Marisa Elena; Foster, E. Michael; Vitiello, Benedetto; Kratochvil, Christopher J.; Burns, Barbara J.; Silva, Susan G.; Reinecke, Mark A.; March, John S.

2009-01-01

Randomized controlled trials that involve 327 participants aged 12 to 18 who were diagnosed with major depression were given either fluoxetine alone, cognitive-behavioral therapy, or a combination of both. Cost-effectiveness acceptability curves suggest that combination treatment is highly likely to be the most cost-effective treatment than…

A combined treatment of UV-light and radio frequency electric field for the inactivation of Escherichia coli K-12 in apple juice

USDA-ARS?s Scientific Manuscript database

Radio frequency electric fields (RFEF) and UV-light treatments have been reported to inactivate bacteria in liquid foods. However, information on the efficacy of bacterial inactivation by combined treatments of RFEF and UV-light technologies is limited. In this study, we investigated the relationshi...

[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.

The effect of EDTA, EGTA, EDTAC, and tetracycline-HCl with and without subsequent NaOCl treatment on the microhardness of root canal dentin.

PubMed

Sayin, Taner Cem; Serper, Ahmet; Cehreli, Zafer C; Otlu, Harika G

2007-09-01

The purpose of this study was to evaluate the effect of single and combined use of ethylenediamine tetra acetic acid (EDTA), ethylene glycol bis [b-aminoethylether] N,N,N',N'-tetraacetic acid (EGTA), EDTA plus Cetavlon (EDTAC), tetracycline-HCl, and NaOCl on the microhardness of root canal dentin. The crowns of 30 single-rooted human teeth were discarded at the cementoenamel junction and the roots were bisected longitudinally to obtain root halves (N = 60). The specimens were embedded in autopolymerizing acrylic resin, leaving the root canal dentin exposed. Dentin surfaces were prepared for microhardness test by grinding and polishing. The reference microhardness values of untreated specimens were recorded using a Vicker's microhardness tester at the apical, midroot, and cervical levels of the root canal. Thereafter, the specimens treated with single (test solution only) or combined (test solution, followed by 2.5% NaOCl) versions of the irrigants for 5 minutes. Posttreatment microhardness values were obtained as with initial ones. Statistical comparisons between the test groups and among single and combined treatments were carried out using 2-way ANOVA with repeated measures (P =.05). Comparisons within each group with respect to application regions were made with Friedman's nonparametric 2-way analysis of variance at the same level of significance. All treatment regimens except distilled water significantly decreased the microhardness of the root canal dentin (P < . 05). The single and combined use of EDTA decreased the microhardness of the root canal dentin significantly more than all other treatment regimens (P < .05). Compared with their single-treatment versions, all combined treatment regimens decreased the mean microhardness values significantly (P < .05). A comparison of single and combined treatment regimens revealed significant decreases only for EDTA and EDTA + NaOCl in the coronal region and for EDTAC and EDTAC + NaOCl in the apical and middle regions of the root canal (P < .05). The use of EDTA alone or prior to NaOCl resulted in the maximum decrease in dentin microhardness. The softening effect of subsequent NaOCl treatment was both material and region dependent. However, for combined treatment regimens, subsequent use of NaOCl levels the statistical differences between the regional microhardness values obtained after treatment with EGTA, EDTAC, and tetracycline-HCl.

The chemical and mechanical effects of binding chitosan to implant quality titanium

NASA Astrophysics Data System (ADS)

Martin, Holly Joy

Biomedical implants are commonly made from commercially pure titanium and other metal alloys, which are chosen for their strength and density. To improve the stability and promote bone cell growth into the implant, efforts to bond coatings to metal have been extensively studied. Many coatings used are considered bioactive, which promote the adhesion and growth of the bone cells surrounding the implant [A.1]. Of these, the most commonly investigated coating is a ceramic called hydroxyapatite, which is brittle, leading to flaking and inadequate bone cell growth [A.2]. Alternate bioactive coatings are being examined, including chitosan, the deacetylated form of chitin. Chitin is the second most abundant polymer in nature [A.3] and is found in the exoskeletons of insects and shellfish [A.4]. Chitosan has been proven to have excellent biocompatibility [A.5], be non-toxic [A.3], and promote the adhesion and growth of bone cells [A.6 - A.7]. In this research, four treatment combinations were developed and tested in an attempt to improve film bonding. These treatment combinations were created using one of two silane molecules, aminopropyltriethoxysilane and triethoxsilylbutyraldehyde, and one of two metal treatments, passivation and piranha treatment. XPS was used to characterize the reaction steps for each of the treatment combinations. A significant decrease in TiO, along with significant increases in SiO x groups, C - N - H, and C = O, indicated that the reactions were proceeding as expected. XPS also indicated that, chemically, the chitosan films were not significantly different and were unchanged by the treatment combinations. Following chemical analysis, mechanical testing was performed on the four treatment combinations. No changes to the bulk properties were seen as demonstrated by nano-indentation, further indicating that the four treatment combinations did not change the chemical properties of chitosan. The bulk adhesion of the films was greatly improved for all four treatment combinations, as demonstrated by tensile testing. The highest value from this research, 19.50 +/- 1.63 MPa, was significantly higher than the previously published results of 1.6-1.8 MPa [A.10]. Overall, the treatments developed in this study significantly improved the adhesion of the chitosan film on the titanium substrate, without modifying the chemical or structural properties of chitosan.

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.

Nogo-receptor 1 antagonization in combination with neurotrophin-4/5 is not superior to single factor treatment in promoting survival and morphological complexity of cultured dopaminergic neurons.

PubMed

Seiler, Stefanie; Di Santo, Stefano; Sahli, Sebastian; Andereggen, Lukas; Widmer, Hans Rudolf

2017-08-01

Cell transplantation using ventral mesencephalic tissue is an experimental approach to treat Parkinson's disease. This approach is limited by poor survival of the transplants and the high number of dopaminergic neurons needed for grafting. Increasing the yield of dopaminergic neurons in donor tissue is of great importance. We have previously shown that antagonization of the Nogo-receptor 1 by NEP1-40 promoted survival of cultured dopaminergic neurons and exposure to neurotrophin-4/5 increased dopaminergic cell densities in organotypic midbrain cultures. We investigated whether a combination of both treatments offers a novel tool to further improve dopaminergic neuron survival. Rat embryonic ventral mesencephalic neurons grown as organotypic free-floating roller tube or primary dissociated cultures were exposed to neurotrophin-4/5 and NEP1-40. The combined and single factor treatment resulted in significantly higher numbers of tyrosine hydroxylase positive neurons compared to controls. Significantly stronger tyrosine hydroxylase signal intensity was detected by Western blotting in the combination-treated cultures compared to controls but not compared to single factor treatments. Neurotrophin-4/5 and the combined treatment showed significantly higher signals for the neuronal marker microtubule-associated protein 2 in Western blots compared to control while no effects were observed for the astroglial marker glial fibrillary acidic protein between groups, suggesting that neurotrophin-4/5 targets mainly neuronal cells. Finally, NEP1-40 and the combined treatment significantly augmented tyrosine hydroxylase positive neurite length. Summarizing, our findings substantiate that antagonization of the Nogo-receptor 1 promotes dopaminergic neurons but does not further increase the yield of dopaminergic neurons and their morphological complexity when combined with neurotrophin-4/5 hinting to the idea that these treatments might exert their effects by activating common downstream pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

High-flow vascular malformation treatment using ultrasound-guided laser combined with polidocanol sclerotherapy.

PubMed

Zhang, Yan; Zhou, Ping; Li, Lan; Li, Jia-le

2015-07-01

The current treatment for vascular malformations includes surgery, sclerotherapy, and embolization. However, each method has its limitations, such as recurrence, complications, scarring, and radiation exposure. Therefore, identifying an effective, minimally invasive treatment that reduces lesion recurrence is particularly important. We describe in detail a patient who received treatment with ultrasound-guided laser interruption of feeding vessels combined with polidocanol sclerotherapy after the recurrence of forearm high-flow vascular malformation.

Brushkiller to control scrub oak sprouts...combinations of broadcast and individual plant applications tested

Treesearch

T. R. Plumb

1967-01-01

ABSTRACT:Combinations of three annual broadcast and individual plant spray applications of brushkiller (a 50-50 mixture of 2,4-dichloro- and 2,4,5-trichlorophenoxyacetic acid) in water-oil emulsion were compared to find the most effective, economical sequence of treatments to kill sprouting scrub oak (Quercus dumosa Nutt.) plants. No one treatment combination had a...

Evaluation of antifungal activity of carbonate and bicarbonate salts alone or in combination with biocontrol agents in control of citrus green mold.

PubMed

Zamani, M; Sharifi Tehrani, A; Ali Abadi, A Alizadeh

2007-01-01

The aim of this research was to determine if the attacks of green mold on orange could be reduced by edible salts alone or in combination with biocontrol agent. For this purpose toxicity to Pantoea digitatum and practical use of sodium carbonate (SC), sodium bicarbonate (SBC) and potassium carbonate, and potassium bicarbonate alone or in combination with antagonistic bacteria (Pseudomonas fluorescens isolate PN, Bacillus subtilis isolate VHN, Pantoea agglomerans isolate CA) to control green mold were determined. All were fungistatic. SC and SBC were equal and superior to the other salts for control of green mold on oranges inoculated 6h before treatment and were chosen for subsequent trails under cold storage conditions. The biocontrol agents were found completely tolerant to 3% sodium bicarbonate and sodium carbonate at room temperature; although their culturability was reduced by > 1000-fold after 60 min in 1% other salt solutions. Satisfactory results were also obtained with the combined treatment for control of green mold. A significant increase in biocontrol activity of all isolate was observed when combined with sodium carbonate and sodium bicarbonate. The treatments comprising CA combined with SB was as effective as fungicide treatment. Thus, use of sodium bicarbonate treatment at 3% followed by the antagonist P. agglomerans CA could be an alternative to chemical fungicides for control of green mold on oranges.

Protein loss in human hair from combination straightening and coloring treatments.

PubMed

França-Stefoni, Simone Aparecida; Dario, Michelli Ferrera; Sá-Dias, Tânia Cristina; Bedin, Valcinir; de Almeida, Adriano José; Baby, André Rolim; Velasco, Maria Valéria R

2015-09-01

Hair chemical treatments, such as dyeing and straightening products, are known to cause damage that can be assessed by protein loss. The aim of this study was to evaluate the hair protein loss caused by combined chemical treatments (dye and relaxer) using the validated bicinchoninic acid (BCA) method. Three kinds of straighteners, based on ammonium thioglycolate, guanidine hydroxide and sodium hydroxide, were evaluated and the least harmful combination indicated. Caucasian virgin dark brown hair tresses were treated with developed natural brown color oxidative hair dyeing and/or straightening commercial products based on ammonium thioglycolate, sodium hydroxide, or guanidine hydroxide. Protein loss quantification was assessed by the validated BCA method which has several advantages for quantifying protein loss in chemically treated hair. When both treatments (straightening and dyeing) were combined, a higher negative effect was observed, particularly for dyed hair treated with sodium hydroxide. In this case, a 356% increase in protein loss relative to virgin hair was observed and 208% in relation to only dyed hair. The combination of dying and relaxers based on ammonium thioglycolate or guanidine hydroxide caused a small increase in protein loss, suggesting that these straightening products could be the best alternatives for individuals wishing to combine both treatments. These results indicated that when application of both types of products is desired, ammonium thioglycolate or guanidine hydroxide should be chosen for the straightening process. © 2015 Wiley Periodicals, Inc.

Enhancements in crystallinity, thermal stability, tensile modulus and strength of sisal fibres and their PP composites induced by the synergistic effects of alkali and high intensity ultrasound (HIU) treatments.

PubMed

Krishnaiah, Prakash; Ratnam, Chantara Thevy; Manickam, Sivakumar

2017-01-01

In this investigation, sisal fibres were treated with the combination of alkali and high intensity ultrasound (HIU) and their effects on the morphology, thermal properties of fibres and mechanical properties of their reinforced PP composites were studied. FTIR and FE-SEM results confirmed the removal of amorphous materials such as hemicellulose, lignin and other waxy materials after the combined treatments of alkali and ultrasound. X-ray diffraction analysis revealed an increase in the crystallinity of sisal fibres with an increase in the concentration of alkali. Thermogravimetric results revealed that the thermal stability of sisal fibres obtained with the combination of both alkali and ultrasound treatment was increased by 38.5°C as compared to the untreated fibres. Morphology of sisal fibre reinforced composites showed good interfacial interaction between fibres and matrix after the combined treatment. Tensile properties were increased for the combined treated sisal fibres reinforced PP composites as compared to the untreated and pure PP. Tensile modulus and strength increased by more than 50% and 10% respectively as compared to the untreated sisal fibre reinforced composite. It has been found that the combined treatment of alkali and ultrasound is effective and useful to remove the amorphous materials and hence to improve the mechanical and thermal properties. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of rotigotine-loaded microspheres and their combination use with L-DOPA to modify dyskinesias in 6-OHDA-lesioned rats.

PubMed

Wang, Aiping; Wang, Lexi; Sun, Kaoxiang; Liu, Wanhui; Sha, Chunjie; Li, Youxin

2012-09-01

To prepare rotigotine loaded microspheres (RoMS) to achieve continuous dopaminergic stimulation (CDS) for the treatment of Parkinson's disease (PD) and investigate both the therapeutic benefit and inducibility of AIMs of administration of RoMS combination with L-DOPA in 6-OHDA-leisioned rats. Rotigotine was encapsulated into poly(lactic-co-glycolic acid) (PLGA) microspheres by an oil-in-water emulsion solvent evaporation technique. In vitro characteristics and in vivo pharmacokinetics of RoMS either in rat blood or brain (by microdialysis) were investigated. Contraversive rotations and AIMs were observed to investigate the therapeutic benefit and the propensity to induce dyskinesia of RoMS or RoMS combination with L-DOPA in 6-OHDA-lesioned rats. RoMS displayed continuous-release characteristics of rotigotine in animals and exhibited a steady efficacy lasted for 2 weeks in 6-OHDA-lesioned rats. No significant difference of the therapeutic benefit between the treatment of RoMS and pulsatile L-DOPA combination and mono L-DOPA was found. While the dyskinesia was significantly decreased with the treatment of RoMS and pulsatile L-DOPA combination compared to mono L-DOPA. RoMS could supply an alternative of CDS for the treatment of PD and the study indicates a potential advantage of RoMS for the treatment of mild and advanced PD patient in combination with L-DOPA.

A self-controlled study of intralesional injection of diprospan combined with topical timolol cream for treatment of thick superficial infantile hemangiomas.

PubMed

Xu, Peng; Yu, Qian; Huang, Huizhen; Zhang, Wenjie; Li, Wei

2018-04-30

Topical application of timolol cream is effective and convenient for treating superficial infantile hemangiomas. Intralesional injection of corticosteroids, such as diprospan, is useful for the treatment of superficia infantile hemangiomas without systemic side effects. We conducted a self-controlled study to investigate whether a combination of intralesional injection of diprospan with topical timolol 0.5% cream would be more efficient than timolol cream alone in thick superficial infantile hemangiomas. Thirty-eight patients with 39 thick superficial infantile hemangiomas were recruited. Each lesion was randomly divided into two equal parts: one part was treated with topical timolol 0.5% cream (timolol cream group), while the other part was treated with injection of diprospan combined with topical timolol 0.5% cream (combined treatment group). Infants were followed every 4 weeks to determine whether injections should be continued, and timolol cream was applied four times daily for 5 months. During 5 months of treatment, three specialist physicians were invited to evaluate the therapeutic effects. The combined treatment group showed better lesion involution than did the timolol cream group regarding lesion thickness and color of lesions. The combination of intralesional injection of diprospan with topical timolol 0.5% cream is a suitable and safe strategy for thick superficial infantile hemangiomas. © 2018 Wiley Periodicals, Inc.

Memantine and donepezil: a fixed drug combination for the treatment of moderate to severe Alzheimer's dementia.

PubMed

Owen, R T

2016-04-01

Donepezil (and other cholinesterase inhibitors [ChEIs]) and memantine are the mainstays of treatment in Alzheimer's dementia, addressing respectively, the cholinergic and glutamatergic dysregulation which underlies or results from its pathophysiology. To alleviate the pill burden and swallowing difficulties associated with the condition, a fixed drug combination of extended-release memantine and donepezil was developed. This combination was shown to be both bioequivalent to the components administered separately and could be administered sprinkled over soft food. The mode of action, pharmacokinetics, clinical efficacy and safety and tolerability of the combination are discussed together with the wider, often conflicting trial literature of combination versus monotherapy with memantine and ChEIs, their meta-analyses and treatment guidelines. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

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.

[A paclitaxel-resistant case of recurrent breast cancer responded to combination therapy of capecitabine and trastuzumab].

PubMed

Marutaka, Masahito; Suguri, Takayasu; Miyake, Mikio; Yoshimura, Kouichi

2005-12-01

The patient was a 72-year-old female. Under the supervision of her former doctor, this patient had an operation and adjuvant chemotherapy for progressive breast cancer. During the following period, local recurrence of breast cancer and pulmonary lymphopathia developed. Although medication with paclitaxel was attempted, the focus was resistant to this treatment, and metastasis to the brain was also observed. Due to the dyscrasia above, the patient had difficulty breathing and became bedridden. Subsequently, combination treatment of capecitabine and trastuzumab was attempted. As a result,metastasis in the brain and pulmonary lymphopathia were improved. The patient recovered enough to be discharged at one time. However, his condition took a turn for the worse after the interruption of the combination treatment by a side effect. In conclusion, the combination treatment of capecitabine and trastuzumab is thought to be effective for non-responders to paclitaxel.

Effects of catechins and caffeine on the development of atherosclerosis in mice.

PubMed

Liu, Litong; Nagai, Izumi; Gao, Ying; Matsushima, Yoshibumi; Kawai, Yoshichika; Sayama, Kazutoshi

2017-10-01

Atherosclerosis is one of the diseases related to metabolic syndrome which is caused by obesity. Previous reports have shown that green tea and its components have anti-obesity effect. We examined whether catechins and caffeine can prevent the development of atherosclerosis by oral administration, singly or in combination to the atherosclerosis model mice. Results demonstrated that the number of atherosclerotic regions in the aorta was significantly reduced by the combined treatment, and the atherosclerotic area was also improved. Serum HDL-C increased by caffeine single treatment, but no effect on the TG and TC by any treatments. Moreover, ECG illuviated to atheromatous lesions in aorta and the illuviation was enhanced by caffeine. The mRNA expression levels of LOX-1 and TNF-α showed a tendency to suppress by the combined treatment. These results indicated that the combined administration of catechins and caffeine has the inhibitory effect on the development of atherosclerosis in mice.

Doxycycline synergizes with doxorubicin to inhibit the proliferation of castration-resistant prostate cancer cells.

PubMed

Zhu, Chao; Yan, Xueting; Yu, Ao; Wang, Yongjian

2017-11-01

Castration-resistant prostate cancer (CRPC) is fatal and there is currently no effective clinical treatment. The antibiotic doxycycline has shown anti-cancer effect in several kinds of solid tumors including prostate cancer. In this study, a combination of doxycycline and doxorubicin was used to investigate the synergistic effect on CRPC cells. MTT assay was employed to determine the viability of cells in two-dimensional (2D) cultures. Apoptosis was determined by Annexin V/propidium iodide (PI) double staining assay. Cell cycle was analyzed by PI staining, and reverse transcription-PCR (RT-PCR) was used to determine the expressions of apoptosis-related genes at mRNA level. Western blot analysis was used to analyze the expressions of Bcl-2, Bax, and Poly (ADP-ribose) polymerase proteins. Cytotoxicity assay and morphological observation of PC3 cells in three-dimensional (3D) cultures were used to determine the effect of combination treatment. Results showed that doxycycline combined with doxorubicin significantly inhibited PC3 cells in both 2D and 3D cultures, enhanced apoptosis, and increased the accumulation of cells in G2/M phase. RT-PCR showed down-regulation of Bcl-2 and up-regulation of Bax mRNA after combination treatment. Meanwhile, western blot analysis showed that combination treatment resulted in down-regulation of Bcl-2 protein and up-regulation of Bax protein, and that PARP cleavage was obviously exhibited after combination treatment. Confocal imaging analysis indicated that doxorubicin penetrated deeply into the core of spheroids when combined with doxycycline. These data indicated that doxycycline in combination with doxorubicin had a synergistic effect on PC3 cells and may provide a potential novel strategy for the treatment of CRPC. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

PubMed Central

Solís García del Pozo, Julián; Solera, Javier

2012-01-01

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

Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms

PubMed Central

Chaudhry, Waqas Nasir; Concepción-Acevedo, Jeniffer; Park, Taehyun; Andleeb, Saadia; Bull, James J.

2017-01-01

In contrast to planktonic cells, bacteria imbedded biofilms are notoriously refractory to treatment by antibiotics or bacteriophage (phage) used alone. Given that the mechanisms of killing differ profoundly between drugs and phages, an obvious question is whether killing is improved by combining antibiotic and phage therapy. However, this question has only recently begun to be explored. Here, in vitro biofilm populations of Pseudomonas aeruginosa PA14 were treated singly and with combinations of two phages and bactericidal antibiotics of five classes. By themselves, phages and drugs commonly had only modest effects in killing the bacteria. However some phage-drug combinations reduced bacterial densities to well below that of the best single treatment; in some cases, bacterial densities were reduced even below the level expected if both agents killed independently of each other (synergy). Furthermore, there was a profound order effect in some cases: treatment with phages before drugs achieved maximum killing. Combined treatment was particularly effective in killing in Pseudomonas biofilms grown on layers of cultured epithelial cells. Phages were also capable of limiting the extent to which minority populations of bacteria resistant to the treating antibiotic ascend. The potential of combined antibiotic and phage treatment of biofilm infections is discussed as a realistic way to evaluate and establish the use of bacteriophage for the treatment of humans. PMID:28076361

Social learning requires plasticity enhanced by fluoxetine through prefrontal Bdnf-TrkB signaling to limit aggression induced by post-weaning social isolation

PubMed Central

Umemori, Juzoh; Tóth, Máté; Biró, László; Miskolczi, Christina; Balázsfi, Diána; Zelena, Dóra; Castrén, Eero

2017-01-01

Escalated or abnormal aggression induced by early adverse experiences is a growing issue of social concern and urges the development of effective treatment strategies. Here we report that synergistic interactions between psychosocial and biological factors specifically ameliorate escalated aggression induced by early adverse experiences. Rats reared in isolation from weaning until early adulthood showed abnormal forms of aggression and social deficits that were temporarily ameliorated by re-socialization, but aggression again escalated in a novel environment. We demonstrate that when re-socialization was combined with the antidepressant fluoxetine, which has been shown to reactivate juvenile-like state of plasticity, escalated aggression was greatly attenuated, while neither treatment alone was effective. Early isolation induced a permanent, re-socialization resistant reduction in Bdnf expression in the amygdala and the infralimbic cortex. Only the combined treatment of fluoxetine and re-socialization was able to recover Bdnf expression via epigenetic regulation. Moreover, the behavior improvement after the combined treatment was dependent on TrkB activity. Combined treatment specifically strengthened the input from the ventral hippocampus to the mPFC suggesting that this pathway is an important mediator of the beneficial behavioral effects of the combined psychosocial and pharmacological treatment of abnormal aggression. Our findings suggest that synergy between pharmacological induction of plasticity and psychosocial rehabilitation could enhance the efficacy of therapies for pathological aggression. PMID:28685757

Cigarette Smoking Predicts Differential Benefit from Naltrexone for Alcohol Dependence

PubMed Central

Fucito, Lisa M.; Park, Aesoon; Gulliver, Suzy Bird; Mattson, Margaret E.; Gueorguieva, Ralitza V.; O’Malley, Stephanie S.

2012-01-01

Background Identifying factors that modify responsiveness to pharmacotherapies for alcohol dependence is important for treatment planning. Cigarette smoking predicts more severe alcohol dependence and poorer treatment response in general. Nevertheless, there is limited research on cigarette smoking as a potential predictor of differential response to pharmacological treatment of alcoholism. Methods We examined the association between cigarette smoking and drinking outcomes in the COMBINE study, a randomized, double-blind placebo-controlled 16-week trial comparing combinations of medications (i.e., acamprosate and naltrexone) and behavioral interventions (i.e., medical management (MM), combined behavioral therapy (CBI)) in 1383 alcohol dependent individuals. Results Smokers (i.e., more than half the sample) significantly differed from nonsmokers on several demographic and drinking-related variables at baseline and generally had poorer treatment outcomes than nonsmokers. However, smokers who received naltrexone had better drinking outcomes than smokers who received placebo, whereas alcohol use among nonsmokers did not vary by naltrexone assignment. This pattern of findings occurred independent of whether patients received CBI or MM and remained after controlling for alcoholism typology and baseline demographic differences. Approximately 9% of smokers quit smoking and an additional 10% reduced their cigarette intake during treatment. Reductions in smoking did not vary by treatment assignment. Conclusions These results suggest that naltrexone may be particularly beneficial for improving alcohol use outcomes in alcohol dependent smokers. Trial Registration The COMBINE Study, NCT000626, http://www.cscc.unc.edu/combine/. PMID:22541040

A randomized, open-label pilot of the combination of low-level laser therapy and lorcaserin for weight loss.

PubMed

Croghan, Ivana T; Ebbert, Jon O; Schroeder, Darrell R; Hurt, Ryan T; Hagstrom, Victoria; Clark, Matthew M

2016-01-01

Obesity is a significant public health problem and innovative treatments are needed. The purpose of this pilot study was to assess the preliminary efficacy and safety of a combined treatment of low-level laser therapy (LLLT) and lorcaserin on weight loss, health quality of life (QOL) measures, and cardiovascular risk factors. Forty-five overweight and obese adult participants with a body mass index (BMI) >26.9 and <40 were randomized to receive LLLT, lorcaserin, or a combination of the two therapies. All study participants received treatment for 3 months and were followed for 3 months post-treatment. Participants were recruited from June 2014 through September 2014. The majority of the 44 participants accrued to this study were female (84 %) with an average age of 43.9 years (range 22 to 64 years). Most participants (93 % LLLT alone, 87 % LLLT + lorcaserin) completed at least 80 % of the LLLT treatments. From baseline to end of treatment, significant reductions in waist circumference were noted for each treatment group (-2.3 ± 4.1 cm, -6.0 ± 7.3 cm, and -4.0 ± 5.5 cm for LLLT, lorcaserin and combination respectively); however, the reduction in body weight was only significant in those receiving lorcaserin and combination treatment (-0.4 ± 1.5 kg, -1.3 ± 1.2 kg and -1.3 ± 1.3 kg). No significant differences were noted between the groups. Self-reported satisfaction was higher in the lorcaserin versus the LLLT group. This small pilot demonstrates that when combined with behavioral intervention, Lorcaserin and LLLT may be effective components of a comprehensive approach to the treatment of overweight and obesity in the clinical setting. Further studies with larger sample size and longer duration of treatment and follow-up are needed to further address efficacy. Trial registration: NCT02129608. Registered June 15, 2014.

Effect of fentanyl and lidocaine on the end-tidal sevoflurane concentration preventing motor movement in dogs.

PubMed

Suarez, Martin A; Seddighi, Reza; Egger, Christine M; Rohrbach, Barton W; Cox, Sherry K; KuKanich, Butch K; Doherty, Thomas J

2017-01-01

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MAC NM ) in dogs. ANIMALS 6 adult Beagles. PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MAC NM (MAC NM-B ) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MAC NM (MAC NM-T ) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MAC NM measurement for determination of plasma concentrations of fentanyl and lidocaine. RESULTS Mean ± SEM overall MAC NM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MAC NM decreased from MAC NM-B to MAC NM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination. CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MAC NM of sevoflurane in dogs.

Metabolomic Profiling of the Synergistic Effects of Melittin in Combination with Cisplatin on Ovarian Cancer Cells

PubMed Central

Alonezi, Sanad; Tusiimire, Jonans; Wallace, Jennifer; Dufton, Mark J.; Parkinson, John A.; Young, Louise C.; Clements, Carol J.; Park, Jin-Kyu; Jeon, Jong-Woon; Ferro, Valerie A.; Watson, David G.

2017-01-01

Melittin, the main peptide present in bee venom, has been proposed as having potential for anticancer therapy; the addition of melittin to cisplatin, a first line treatment for ovarian cancer, may increase the therapeutic response in cancer treatment via synergy, resulting in improved tolerability, reduced relapse, and decreased drug resistance. Thus, this study was designed to compare the metabolomic effects of melittin in combination with cisplatin in cisplatin-sensitive (A2780) and resistant (A2780CR) ovarian cancer cells. Liquid chromatography (LC) coupled with mass spectrometry (MS) was applied to identify metabolic changes in A2780 (combination treatment 5 μg/mL melittin + 2 μg/mL cisplatin) and A2780CR (combination treatment 2 μg/mL melittin + 10 μg/mL cisplatin) cells. Principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) multivariate data analysis models were produced using SIMCA-P software. All models displayed good separation between experimental groups and high-quality goodness of fit (R2) and goodness of prediction (Q2), respectively. The combination treatment induced significant changes in both cell lines involving reduction in the levels of metabolites in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, purine and pyrimidine metabolism, and the arginine/proline pathway. The combination of melittin with cisplatin that targets these pathways had a synergistic effect. The melittin-cisplatin combination had a stronger effect on the A2780 cell line in comparison with the A2780CR cell line. The metabolic effects of melittin and cisplatin in combination were very different from those of each agent alone. PMID:28420117

Impact of methylene blue and atorvastatin combination therapy on the apparition of cerebral malaria in a murine model.

PubMed

Dormoi, Jérome; Briolant, Sébastien; Desgrouas, Camille; Pradines, Bruno

2013-04-15

Proveblue®, a methylene blue dye that complies with European Pharmacopoeia and contains limited organic impurities and heavy metals of recognized toxicity, showed in vitro synergy against Plasmodium falciparum when combined with atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase. The objective of this study was to evaluate the in vivo efficacy of Proveblue® when combined with atorvastatin in a murine model of experimental cerebral malaria. Forty female C57Bl6/N mice were divided into four groups (control, atorvastatin 40 mg/kg for seven days, Proveblue® 10 mg/kg for five days and atorvastatin combined with Proveblue®), infected with Plasmodium berghei ANKA parasites by intraperitoneal inoculation and observed for 45 days. Treatment with atorvastatin alone did not demonstrate an effect significantly different from no treatment (p = 0.0573). All the mice treated by atorvastatin alone died. Treatment with Proveblue® or a combination of Proveblue® and atorvastatin was significantly increased survival of cerebral malaria (p = 0.0011 and 0.0002, respectively). Although there was only one death in the atorvastatin and Proveblue® combination treatment group (10%) versus two deaths (22%) with Proveblue® treatment, the effect on cerebral malaria was not significant (p = 0.283). The present work demonstrated, for the first time, the high efficacy of Proveblue® in preventing cerebral malaria. Atorvastatin alone or in combination appears to possess limited use for preventing cerebral malaria. Combination of atorvastatin with lower doses of Proveblue® (<10 mg/kg/day) should be evaluated to show potential synergistic effects in cerebral malaria prevention.

Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

PubMed Central

Arnold, L. Eugene; Hodgkins, Paul; Caci, Hervé; Kahle, Jennifer; Young, Susan

2015-01-01

Background Evaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood. Methods A systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment. Results The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length. Conclusions While the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age or longer durations did not markedly affect proportion of improved outcomes reported, but measurement of outcomes long periods after treatment cessation may attenuate results. PMID:25714373

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

PubMed

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

2015-11-25

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

Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension.

PubMed

Reddi, A S; Nimmagadda, V R; Arora, R

2001-05-01

We have previously demonstrated that antihypertensive treatment with doxazosin (DZN), an alpha-adrenergic blocker, and lisinopril (LIS), an ACE inhibitor, reverse glomerular sclerosis in corpulent spontaneously hypertensive rats with type 2 diabetes. In this study, we examined the effects of the above-mentioned antihypertensive drugs alone and in combination on the structure of interlobular and arcuate arteries in these rats. Both male and female rats aged 6 months were treated with antihypertensive drugs for 16 weeks. Various structural parameters were evaluated by light microscopy, with the use of digital image analysis, in kidney sections stained with periodic acid-SCHIFF: Systolic blood pressure was significantly lower in treated than in untreated rats. Untreated diabetic rats had a significantly higher media/lumen ratio (smaller luminal diameter) of both arteries compared with the ratio in treated rats (for interlobular artery, 0.72+/-0.06 [no treatment], 0.49+/-0.03 [DZN treatment], 0.54+/-0.06 [LIS treatment], and 0.52+/-0.04 [combination therapy], P<0.05 to <0.001 for no treatment versus treatment; for arcuate artery, 0.66+/-0.11 [no treatment], 0.40+/-0.02 [DZN treatment], 0.39+/-0.04 [LIS treatment], and 0.40+/-0.03 [combination therapy], P<0.05 for no treatment versus treatment). Antihypertensive treatment caused significant increases in total arterial cross-sectional area, internal and external diameters, luminal and medial cross-sectional area, and medial thickness in both interlobular and arcuate arteries. The improvement in arterial structure after antihypertensive treatment was due to remodeling and growth of the vessels. Both DZN and LIS were equally efficacious, and combination therapy had no additive or synergistic effect.

Gold Rods Irradiated with Ultrasound for Combination of Hyperthermia and Cancer Chemotherapy.

PubMed

Barros, Andre; Austerlitz, Carlos; Gkigkitzis, Ioannis; Campos, Diana; Andrade, Jeyce; Peixoto, Christina; Aguiar, Jaciana; Nascimento, Silene; Silva, Teresinha G; Haranas, Ioannis

2017-01-01

The aim of this study was to analyze feasibility (in vitro and in vivo) the use of hyperthermia produced by gold rods irradiated with ultrasound and their combination with chemotherapy with doxorubicin. initially was determined the cell viability and Hsp70 levels after treatment by gold rods irradiated with ultrasound (GR+U) in cell culture. The pretreatment with GR+U combined with doxorubicin (DOX) was evaluated from IC 50 , caspase-3 expression and mechanisms of cell death by electron microscopy. For evaluate the in vivo effects was used solid Ehrlich carcinoma (SEC) Tumor. The animals received three treatments with the combination of GR+U+DOX over 16 days. The cell viability was completely inhibited after 40 min of treatment with GR+U and significant increases the expression of HSP70 was only observed after 10 min of treatment. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. GR+U+DOX presented significant reduction of IC 50 representing 50.7%, 76.5% 45.2% and 46.6% for cell lines K562, NCI-H292, Hep-2 and MCF-7 respectively. The caspase-3 level and ultraestructural analysis showed that treatment with GR+U+DOX enhances induction of apoptosis. Pretreatment with GR+U combined with doxorubicin (1 mg) showed 87% inhibition against SEC. and no showed cardiotoxic effect. The combined treatment of GR+U and DOX exhibit synergistic characteristics observed by increasing the efficiency of doxorubicin.

A small molecule norspermidine in combination with silver ion enhances dispersal and disinfection of multi-species wastewater biofilms.

PubMed

Wu, Yachuan; Quan, Xiangchun; Si, Xiurong; Wang, Xinrui

2016-06-01

Detrimental biofilms have become a great concern in many areas due to their strong resistance and insensitivity to traditional antimicrobial agents. Norspermidine is a potent small molecule for biofilm dispersal. In this study, silver ion, a conventional inorganic biocide, was combined with norspermidine and used for control and removal of multi-species biofilms formed by a mixed culture from wastewater treatment systems. Results showed that silver ion (0.01-1 mg/L) treatment alone failed to remove the existing wastewater biofilms. Norspermidine at the concentrations of 500-1000 μM was capable to disrupt and disperse the existing biofilms with a biofilm reduction of 21-34 % after 24-h exposure. The combined treatment with norspermidine (500 μM) and silver ion (0.01 mg/L) increased biofilm reduction to 48 % (24-h exposure). The combined treatment also enhanced biofilm disinfection ratio (82 %, 2-h exposure) by 2.0- and 2.6-folds compared to norspermidine (27 %) or silver ion (23 %) treatment alone, respectively. Confocal laser scanning microscopic (CLSM) observations found that norspermidine could disrupt biofilm matrix and promote biofilm dispersal via breaking down exopolysaccharides. The combined treatment increased the reduction in biofilm cell density and viability, possibly due to the damage of biofilm matrix, enhanced silver ion diffusion in biofilms, and increased biofilm sensitivity. These findings indicate that the combination of a small molecule norspermidine with a traditional biocide silver ion presents a novel strategy to remove and kill biofilms, which have a potential application in addressing wastewater biofilm-related issues.

Acupuncture combined with Chinese herbs for the treatment in hemivertebral French bulldogs with emergent paraparesis.

PubMed

Liu, Ching Ming; Holyoak, G Reed; Lin, Chung Tien

2016-10-01

This study follows the treatment of six French bulldogs with paraparesis caused by congenital hemivertebra which were structurally mild but clinically severe. A standardized acupuncture ( zhēn jiǔ) treatment using Hua-Tuo-Jiaji (HTJJ) as local points and other distant points combined with Chinese herbs improved the clinical signs. Few, if any, published papers mention Traditional Chinese Veterinary Medicine (TCVM) for treatment of hemivertebral paraparesis in French bulldogs. Based on the rapid treatment outcome, we encourage practitioners to integrate this form of conservative management into emergency treatment.

Effect of ultraviolet light irradiation and sandblasting treatment on bond strengths between polyamide and chemical-cured resin.

PubMed

Asakawa, Yuya; Takahashi, Hidekazu; Iwasaki, Naohiko; Kobayashi, Masahiro

2014-01-01

The aim of this study was to evaluate the effects of ultraviolet light (UV) irradiation and sandblasting treatment on the shear bond strength between polyamide and chemical-cured resin. Three types of commercial polyamides were treated using UV irradiation, sandblasting treatment, and a combining sandblasting and UV irradiation. The shear bond strength was measured and analyzed using the Kruskal-Wallis test (α=0.05). Comparing shear bond strengths without surface treatment, from 4.1 to 5.7 MPa, the UV irradiation significantly increased the shear bond strengths except for Valplast, whose shear bond strengths ranged from 5.2 to 9.3 MPa. The sandblasting treatment also significantly increased the shear bond strengths (8.0 to 11.4 MPa). The combining sandblasting and UV irradiation significantly increased the shear bond strengths (15.2 to 18.3 MPa) comparing without surface treatment. This combined treatment was considered the most effective at improving the shear bond strength between polyamide and chemical-cured resin.

Treatment preference among suicidal and self-injuring women with borderline personality disorder and PTSD.

PubMed

Harned, Melanie S; Tkachuck, Mathew A; Youngberg, Kelly A

2013-07-01

This study examined treatment preferences among suicidal and self-injuring women with borderline personality disorder (BPD) and PTSD. Women (N = 42, M(age) = 34) with BPD, PTSD and recent intentional self-injury were evaluated upon entry into a psychotherapy outcome study. The majority preferred a combined dialectical behavior therapy (DBT) and prolonged exposure (PE) treatment (73.8%), followed by DBT alone (26.2%), and PE alone (0%). Women who preferred the combined treatment were more likely to report a desire to obtain relief from PTSD and to receive specific DBT and PE treatment components as reasons underlying this preference. Few women (21.4%) reported concerns about PE, but those who did were more likely to prefer DBT alone. More severe PTSD re-experiencing symptoms, a childhood index trauma, and less reduction in positive affect after a trauma interview predicted a preference for the combined treatment. These results may help to inform treatment for these complex patients. © 2013 Wiley Periodicals, Inc.

Erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) combined responders to tadalafil after 12 weeks of treatment.

PubMed

Roehrborn, Claus G; Egan, Kathryn B; Miner, Martin M; Ni, Xiao; Wong, David G; Rosen, Raymond C

2016-07-01

To analyse the proportion of men taking tadalafil 5 mg once daily who experience a combined improvement in symptoms of both erectile dysfunction (ED) and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). The data from men aged ≥45 years randomized to tadalafil 5 mg once daily or placebo enrolled in one of four randomized, placebo-controlled LUTS/BPH clinical trials were analysed (N = 927). A novel classification of 'combined responders' to ED and LUTS/BPH treatment was defined, based on published criteria for men who showed improvement in both International Index of Erectile Function - Erectile Function domain (IIEF-EF) score and total International Prostate Symptom Score (IPSS). Descriptive analyses assessed the covariate distribution by responder status. Unadjusted and adjusted logistic regressions provided odds ratios with 95% confidence intervals comparing combined responders with all others (partial and non-responders). Among men randomized to tadalafil 5 mg, 40.5% were combined responders (n = 189). Among placebo randomized men, 18.3% were combined responders (n = 84). Combined responders, in the total population, had the highest baseline IPSS and lowest baseline IIEF-EF scores, corresponding to the highest level of dysfunction. The majority of men were aged ≤65 years, white, non-obese, non-smokers, and regular alcohol consumers. Only treatment, baseline IPSS, baseline IIEF-EF, obesity and psychoactive medication use were significantly associated with responder status (P ≤ 0.05). Tadalafil-treated men had 2.8 times significantly increased adjusted odds of being combined responders vs non-responders (P < 0.001). For each unit decrease in baseline IIEF-EF or alcoholic drink consumption per week there was a 4% significant increase in the adjusted odds of being a combined responder to tadalafil therapy. This novel measure of combined response is useful in differentiating patients with clinically relevant symptom improvement for both ED and LUTS/BPH after treatment with tadalafil 5 mg once daily vs placebo. This combined responder measure may be useful in future assessment of treatment benefits across patient groups after various types of treatment intervention (e.g. surgical vs pharmacotherapy vs non-pharmacological intervention). © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

A 12-year follow-up study of combined treatment of post-severe acute respiratory syndrome patients with femoral head necrosis.

PubMed

Liu, Tiansheng; Ma, Jinchao; Su, Bin; Wang, Hao; Wang, Qi; Ma, Xinlong

2017-01-01

To investigate the long-term efficacy of a combination treatment of alendronate, extracorporeal shock and hyperbaric oxygen for osteonecrosis of the femoral head (ONFH) of post-severe acute respiratory syndrome (SARS) patients. The retrospective study was performed including a total of 37 post-SARS ONFH patients (66 hip joints) in the Department of Orthopedics of the General Hospital of Tianjin Medical University between November 2003 and November 2015, consisting of 6 males (11 hip joints) and 31 females (55 hip joints), with age between 19 and 47 years (average 29.9 years). Visual analog scale (VAS) score, Harris score and Association Research Circulation Osseous (ARCO) stage of imaging examination were compared among those before treatment, and at 1, 3, 6, 9 and 12 years after treatment. Paired t -test was used for statistical analysis of VAS and Harris score before and after treatment. Difference of effective rate on all stages was analyzed with Chi-square test. With 12-year follow-up, significant improvements on VAS (6.81 of pre-treatment vs 3.94 of 12-year post-treatment) and Harris score (74.54 of pre-treatment vs 80.14 of 12-year post-treatment) were observed (all p <0.05). Effective rate showed statistical significance among three stages of ARCO ( p <0.05). The combined treatment showed different efficacies on different ARCO stages; the best was on ARCO Phase I. The combined treatment may delay or discontinue the development of ONFH in post-SARS patients.

[Clinical efficacy of porcine pulmonary surfactant combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome].

PubMed

Tan, Xiu-Zhen; Wu, Shi-Guang; Zhang, Jian-Hua; Li, Xiao-Fen; Gao, Ping-Ming; Wang, Yu

2016-12-01

To study the clinical efficacy of porcine pulmonary surfactant (PS) combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome (MAS). Seventy neonates with MAS were enrolled for a prospective study. The neonates were randomly assigned to PS alone treatment group and PS+budesonide treatment group (n=35 each). The PS alone treatment group was given PS (100 mg/kg) by intratracheal instillation. The treatment group was given budesonide suspension (0.25 mg/kg) combined with PS (100 mg/kg). The rate of repeated use of PS in the PS+ budesonide group was significantly lower than that in the PS alone group 12 hours after treatment (p<0.05). The improvement of PaO 2 /FiO 2 , TcSaO 2 , PaO 2 , and PaCO 2 in the PS+ budesonide group was significantly greater than that in the PS alone group 6, 12, and 24 hours after treatment (p<0.05). The chest X-ray examination showed that the pulmonary inflammation absorption in the PS+ budesonide group was significantly better than that in the PS alone group 48 hours after treatment (p<0.05). The incidence of complications in the PS+budesonide group was significantly lower than that in the PS alone group (p<0.05), and the average hospitalization duration was significantly shorter than that in the PS alone group (p<0.01). PS combined with budesonide suspension intratracheal instillation for the treatment of neonatal MAS is effective and superior to PS alone treatment.

URBAN RUNOFF POLLUTION CONTROL - STATE-OF-THE-ART

EPA Science Inventory

Combined sewer overflows are major sources of water pollution problems, but even discharges of stormwater alone can seriously affect water quality. Current approaches involve control of overflows, treatment, and combinations of the two. Control may involve maximizing treatment wi...

Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization.

PubMed

Cui, X; Chen, J; Zacharek, A; Roberts, C; Savant-Bhonsale, S; Chopp, M

2008-09-22

Neovascularization may contribute to functional recovery after neural injury. Combination treatment of stroke with a nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate (DETA-NONOate) and bone marrow stromal cells promotes functional recovery. However, the mechanisms underlying functional improvement have not been elucidated. In this study, we tested the hypothesis that combination treatment upregulates angiopoietin-1 and its receptor Tie2 in the ischemic brain and bone marrow stromal cells, thereby enhancing cerebral neovascularization after stroke. Adult wild type male C57BL/6 mice were i.v. administered PBS, bone marrow stromal cells 5x10(5), DETA-NONOate 0.4 mg/kg or combination DETA-NONOate with bone marrow stromal cells (n=12/group) after middle cerebral artery occlusion. Combination treatment significantly upregulated angiopoietin-1/Tie2 and tight junction protein (occludin) expression, and increased the number, diameter and perimeter of blood vessels in the ischemic brain compared with vehicle control (mean+ or -S.E., P<0.05). In vitro, DETA-NONOate significantly increased angiopoietin-1/Tie2 protein (n=6/group) and Tie2 mRNA (n=3/group) expression in bone marrow stromal cells. DETA-NONOate also significantly increased angiopoietin-1 protein (n=6/group) and mRNA (n=3/group) expression in mouse brain endothelial cells (P<0.05). Angiopoietin-1 mRNA (n=3/group) was significantly increased in mouse brain endothelial cells treated with DETA-NONOate in combination with bone marrow stromal cell-conditioned medium compared with cells treated with bone marrow stromal cell-conditioned medium or DETA-NONOate alone. Mouse brain endothelial cell capillary tube-like formation assays (n=6/group) showed that angiopoietin-1 peptide, the supernatant of bone marrow stromal cells and DETA-NONOate significantly increased capillary tube formation compared with vehicle control. Combination treatment significantly increased capillary tube formation compared with DETA-NONOate treatment alone. Inhibition of angiopoietin-1 significantly attenuated combination treatment-induced tube formation. Our data indicated that combination treatment of stroke with DETA-NONOate and bone marrow stromal cells promotes neovascularization, which is at least partially mediated by upregulation of the angiopoietin-1/Tie2 axis.

[Clinical trial of a combination of three drugs in fixed proportions in the treatment of tuberculosis. Groupe de Travail sur la Chimiothérapie de la Tuberculose].

PubMed

Chaulet, P; Boulahbal, F

1995-10-01

The Matiben Chest Clinic at the West Algiers University Teaching Hospital, and 3 outpatient clinics specializing in tuberculosis and lung disease in Algiers. To determine the tolerance and efficacy of a fixed proportion combination of 3 antituberculosis drugs (per tablet: 50 mg isoniazid + 120 mg rifampicin + 300 mg pyrazinamide) given during the first 2 months of a daily 6-month chemotherapy regimen. Random prospective treatment trial comparing a group of 124 patients receiving the triple combination with another group of 126 patients receiving the 3 drugs separately during the initial treatment phase. The continuation phase was identical for the 2 groups. Comparison of tolerance in the first 2 months, and of the failure and relapse rates (respectively at the end of treatment and 24 months after the end of treatment). During the first 2 months side-effects were significantly more common in the group receiving the drugs separately. At the end of treatment and during the following 24 months there were no significant differences in the cumulative rates of observed failures and relapses (2% and 1%). The triple combination studied could replace the separate drugs in the initial treatment phase in countries where the bioavailability of the drugs used has been proven.

Treatment of refractory sino-nasal aspergillosis with posaconazole and terbinafine in 10 dogs.

PubMed

Stewart, J; Bianco, D

2017-09-01

To determine the safety and efficacy of posaconazole and terbinafine for the treatment of naturally occurring sino-nasal aspergillosis in dogs refractory to conventional topical and systemic treatment. Ten client-owned dogs with sino-nasal aspergillosis and not responsive to conventional treatments were prospectively enrolled to receive a dose of 5 mg/kg posaconazole orally every 12 hours for six months. All dogs were concurrently treated with doses of 30 mg/kg terbinafine orally every 12 hours and 5 mg/kg doxycycline orally every 12 hours for 6 to 18 months. All 10 enrolled dogs completed the study. The treatment response was defined as complete clinical remission (n=7) or partial clinical remission (n=3). Two dogs relapsed after cessation of combination therapy. All dogs lived more than one year after starting combination therapy and eight dogs are alive at the time of writing. No clinically relevant adverse reactions or increases in hepatic enzyme activity occurred during the combination therapy. The results of this study suggest that this combination therapy appears safe and well-tolerated for the treatment of refractory sino-nasal aspergillosis in dogs. Long-term survival is possible with prolonged treatment, but relapse is possible. Larger prospective studies are warranted to further evaluate these preliminary findings. © 2017 British Small Animal Veterinary Association.

MR-guided pulsed high intensity focused ultrasound enhancement of docetaxel combined with radiotherapy for prostate cancer treatment

NASA Astrophysics Data System (ADS)

Mu, Zhaomei; Ma, C.-M.; Chen, Xiaoming; Cvetkovic, Dusica; Pollack, Alan; Chen, Lili

2012-01-01

The purpose of this study is to evaluate the efficacy of the enhancement of docetaxel by pulsed focused ultrasound (pFUS) in combination with radiotherapy (RT) for treatment of prostate cancer in vivo. LNCaP cells were grown in the prostates of male nude mice. When the tumors reached a designated volume by MRI, tumor bearing mice were randomly divided into seven groups (n = 5): (1) pFUS alone; (2) RT alone; (3) docetaxel alone; (4) docetaxel + pFUS (5) docetaxel + RT (6) docetaxel + pFUS + RT, and (7) control. MR-guided pFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5T GE MR scanner. Animals were treated once with pFUS, docetaxel, RT or their combinations. Docetaxel was given by i.v. injection at 5 mg kg-1 before pFUS. RT was given 2 Gy after pFUS. Animals were euthanized 4 weeks after treatment. Tumor volumes were measured on MRI at 1 and 4 weeks post-treatment. Results showed that triple combination therapies of docetaxel, pFUS and RT provided the most significant tumor growth inhibition among all groups, which may have potential for the treatment of prostate cancer due to an improved therapeutic ratio.

Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice.

PubMed

Bocco, B M; Fernandes, G W; Lorena, F B; Cysneiros, R M; Christoffolete, M A; Grecco, S S; Lancellotti, C L; Romoff, P; Lago, J H G; Bianco, A C; Ribeiro, M O

2016-03-01

Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model.

Efficacy of antibiotic treatment and test-based culling strategies for eradicating brucellosis in commercial swine herds.

PubMed

Dieste-Pérez, L; Frankena, K; Blasco, J M; Muñoz, P M; de Jong, M C M

2016-04-01

Swine brucellosis caused by Brucella suis biovar 2 is an emerging disease in continental Europe. Without effective vaccines being available, the European Food Safety Authority (EFSA) recommends the full depopulation of infected herds as the only strategy to eradicate B. suis outbreaks. Using data collected from 8 herds suffering natural swine brucellosis outbreaks, we assessed the efficacy of four control strategies: (i) oxytetracycline treatment only, as a default scenario, (ii) oxytetracycline treatment combined with skin testing and removal of positive animals, (iii) oxytetracycline treatment combined with serological testing (Rose Bengal test-RBT-and indirect ELISA -iELISA-) and removal of seropositive animals and (iv) oxytetracycline treatment combined with both serological (RBT/iELISA) and skin testing and removal of positive animals. A Susceptible-Infectious-Removal model was used to estimate the reproduction ratio (R) for each strategy. According to this model, the oxytetracycline treatment alone was not effective enough to eradicate the infection. However, this antibiotic treatment combined with diagnostic testing at 4-monthly intervals plus immediate removal of positive animals showed to be effective to eradicate brucellosis independent of the diagnostic test strategy used in an acceptable time interval (1-2 years), depending on the initial number of infected animals. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of combined application of transcranial magnetic stimulation and language training on children with language retardation.

PubMed

Qiu, Aizhen; Li, Xinjian; Yang, Zhongxiu; Li, Zhilin; Wang, Jiping; Yuan, Huanxia; Jin, Xin

2016-10-28

The objective of the present manuscript was to explore the effects of combined application of transcranial magnetic stimulation (TMS) and language training on children with language retardation. Forty-five children with language retardation were selected as subjects and randomly divided into the treatment group with 24 patients and the control group with 21 patients. The control group was treated with traditional language training, while the treatment group was treated with TMS combined with language training. According to Gesell pediatric neuropsychological development schedules, the development quotient of children in the two groups were observed and compared before and after two courses of treatment. The evaluation of mouth movement was conducted with Dr. Speech supervised by East China Normal University. Development quotient scores and mouth movement evaluation scores of all Gesell parameters of children in the two groups after treatment were significantly higher than those before treatment (P<0.05). The body movement ability, linguistic competence, development quotient scores, and mouth movement evaluation scores in the treatment group after treatment were higher than those of the control group, and the differences were statistically significant (P<0.05). The combined application of TMS and language training can effectively improve linguistic competence, action ability, and mouth movement in children with language retardation.

Effects of combined application of organic and inorganic fertilizers plus nitrification inhibitor DMPP on nitrogen runoff loss in vegetable soils.

PubMed

Yu, Qiaogang; Ma, Junwei; Zou, Ping; Lin, Hui; Sun, Wanchun; Yin, Jianzhen; Fu, Jianrong

2015-01-01

The application of nitrogen fertilizers leads to various ecological problems such as large amounts of nitrogen runoff loss causing water body eutrophication. The proposal that nitrification inhibitors could be used as nitrogen runoff loss retardants has been suggested in many countries. In this study, simulated artificial rainfall was used to illustrate the effect of the nitrification inhibitor DMPP (3,4-dimethyl pyrazole phosphate) on nitrogen loss from vegetable fields under combined organic and inorganic nitrogen fertilizer application. The results showed that during the three-time simulated artificial rainfall period, the ammonium nitrogen content in the surface runoff water collected from the DMPP application treatment increased by 1.05, 1.13, and 1.10 times compared to regular organic and inorganic combined fertilization treatment, respectively. In the organic and inorganic combined fertilization with DMPP addition treatment, the nitrate nitrogen content decreased by 38.8, 43.0, and 30.1% in the three simulated artificial rainfall runoff water, respectively. Besides, the nitrite nitrogen content decreased by 95.4, 96.7, and 94.1% in the three-time simulated artificial rainfall runoff water, respectively. A robust decline in the nitrate and nitrite nitrogen surface runoff loss could be observed in the treatments after the DMPP addition. The nitrite nitrogen in DMPP addition treatment exhibited a significant low level, which is near to the no fertilizer application treatment. Compared to only organic and inorganic combined fertilizer treatment, the total inorganic nitrogen runoff loss declined by 22.0 to 45.3% in the organic and inorganic combined fertilizers with DMPP addition treatment. Therefore, DMPP could be used as an effective nitrification inhibitor to control the soil ammonium oxidation in agriculture and decline the nitrogen runoff loss, minimizing the nitrogen transformation risk to the water body and being beneficial for the ecological environment.

Rationale of combination therapy with antioxidants in medical management of Peyronie’s disease: results of clinical application

PubMed Central

Paulis, Gianni; Paulis, Andrea; Romano, Gennaro; Barletta, Davide; Fabiani, Andrea

2017-01-01

Peyronie’s disease (PD) is a connective tissue disorder involving the tunica albuginea of the corpora cavernosa of the penis. We have published several studies describing a “combined therapy” for PD patients, but the present study aims to clearly demonstrate how the association between various antioxidants in PD treatment can significantly increase the likelihood of therapeutic success. We used the following substances: silymarin, ginkgo biloba, vitamin E, bilberry, topical diclofenac sodium, and pentoxifylline (PTX). We analyzed the therapeutic impact and possible side effects of one or more antioxidants in patients with early-stage PD. To clearly prove that it is possible to achieve better results when combining more than one agent, we designed this study with five treatment groups, corresponding, respectively, to the administration of a single oral antioxidant; two oral antioxidants; three oral antioxidants; five oral antioxidants + local diclofenac; and five oral antioxidants + local diclofenac + PTX by perilesional injection. One hundred and twenty patients were assigned to five groups of treatment designed according to the abovementioned study aim. Outcomes after 6 months of treatment showed that combined antioxidant therapy is effective in treating PD. Statistical analysis showed significant differences between the treatment groups with regard to: improvement and disappearance of penile pain; percentage of reduction in the volume of penile plaque; reduction in penile curvature; recovery of erectile function in patients with erectile dysfunction; increase in the International Index of Erectile Function score; and reduction of psychosexual impact. Furthermore, we observed that the clinical efficacy of combined therapy is greater when topical use of diclofenac gel and perilesional injection of PTX are added to oral treatment with more than one antioxidant. Although several articles have already been published reporting the effectiveness of combined treatment in PD, this is the first study clearly proving how, as the number of substances used in treatment rises, a proportionally greater therapeutic effect is achieved. PMID:28791261

Postinfection activity, residue levels, and persistence of azoxystrobin, fludioxonil, and pyrimethanil applied alone or in combination with heat and imazalil for green mold control on inoculated oranges.

PubMed

Schirra, Mario; Palma, Amedeo; Barberis, Antonio; Angioni, Alberto; Garau, Vincenzo Luigi; Cabras, Paolo; D'Aquino, Salvatore

2010-03-24

The postinfection activity of azoxystrobin (AZX), fludioxonil (FLU), and pyrimethanil (PYR), applied alone or in combination with imazalil (IMZ), in controlling postharvest green mold in 'Salustiana' oranges inoculated with Penicillium digitatum was studied. Fruits were immersed for 30 or 60 s in (i) water or water mixtures at 20 degrees C containing AZX, FLU, or PYR at 600 mg/L; and (ii) IMZ at 600 mg/L, alone or in combination with AZX, FLU, or PYR at 600 mg/L. Similar treatments were performed at 50 degrees C using the active ingredients at half rates with respect to the treatments at 20 degrees C. Fungicide residues in fruits were analyzed following treatments and after 14 days of simulated shelf life at 17 degrees C. AZX or FLU mixtures at 20 degrees C for 30-60 s similarly but moderately reduced green mold decay with respect to control fruit; differences due to dip time were not significant. Superior control of decay was achieved by PYR and, especially, IMZ, applied alone or in combination with AZX, FLU, or PYR. The activity of PYR at 20 degrees C was significantly dependent on treatment time, whereas that of IMZ and combined treatments at 20 degrees C was not. The effectiveness of FLU or PYR mixtures at 50 degrees C in controlling decay was similar and superior to that of AZX. The action of single- or double-fungicide application was not dependent on dip time in most samples. IMZ or combined mixtures at 50 degrees C were consistently more effective with respect to single-fungicide treatments with AZX, FLU, or PYR. The application of heated fungicide mixtures resulted in significantly higher residue accumulation in most fruit samples compared to treatments performed at 20 degrees C. The degradation rate of fungicides was generally low and dependent on treatment conditions such as time, temperature, and the presence or not of other fungicides.

Combinatorial effect of curcumin with docetaxel modulates apoptotic and cell survival molecules in prostate cancer

PubMed Central

Banerjee, Saswati; Singh, Santosh K.; Chowdhury, Indrajit; Lillard, James W.; Singh, Rajesh

2017-01-01

Docetaxel is the most commonly used chemotherapeutic agent to target androgen signaling in metastatic prostate cancer (PCa); however, prolonged treatment with docetaxel results in drug-resistant cancer cells. Combination therapies have the potential of increasing the effectiveness of drug treatment as well as decreasing the side effects. Curcumin is a nontoxic organic compound with multifaceted chemopreventive potential. In this study, we evaluated whether curcumin can reinforce the effect of docetaxel on PCa cells. The PCa cell lines DU145 and PC3 were treated with curcumin and docetaxel alone or in combination. After completion of the treatment cell proliferation and the expression of pro-survival and anti-apoptotic markers and the signaling molecules were analyzed. The combined treatment of curcumin and docetaxel inhibited the proliferation and induced apoptosis significantly higher than the curcumin and docetaxel-treated group alone. Interestingly, the combined treatment with curcumin and docetaxel modulates the expression of RTKs, PI3K, phospho-AKT, NF-kappa B, p53, and COX-2. These results suggest that curcumin can be a potential therapeutic contender in enhancing the efficacy of docetaxel in PCa treatment. PMID:28199187

Combined Medication and CBT for Generalized Anxiety Disorder with African American Participants: Reliability and Validity of Assessments and Preliminary Outcomes

PubMed Central

Markell, Hannah M.; Newman, Michelle G.; Gallop, Robert; Gibbons, Mary Beth Connolly; Rickels, Karl; Crits-Christoph, Paul

2014-01-01

Using data from a study of combined cognitive behavioral therapy (CBT) and venlafaxine XR in the treatment of generalized anxiety disorder (GAD), the current article examines the reliability and convergent validity of scales, and preliminary outcomes, for African American compared to European American patients. Internal consistency and short-term stability coefficients for African Americans (n=42) were adequate and similar or higher compared to those found for European Americans (n=164) for standard scales used in GAD treatment research. Correlations among outcome measures among African Americans were in general not significantly different for African Americans compared to European Americans. A subset of patients with DSM-IV–diagnosed GAD (n = 24 African Americans; n = 52 European Americans) were randomly selected to be offered the option of adding 12 sessions of CBT to venlafaxine XR treatment. Of those offered CBT, 33.3% (n = 8) of the African Americans, and 32.6% (n = 17) of the European Americans accepted and attended at least one CBT treatment session. The outcomes for African Americans receiving combined treatment were not significantly different from European Americans receiving combined treatment on primary or secondary efficacy measures. PMID:24912462

Effect of alkali and oxidative treatments on the physicochemical, pasting, thermal and morphological properties of corn starch.

PubMed

Spier, Franciela; Zavareze, Elessandra da Rosa; Marques e Silva, Ricardo; Elias, Moacir Cardoso; Dias, Alvaro Renato Guerra

2013-07-01

Few studies on starch modifications using different chemical agents are available in the literature, and no reports were found on the combined effect of oxidation and alkaline treatment of corn starch. Thus this work evaluated the physicochemical, pasting, morphological, cystallinity and thermal properties of chemically modified corn starch, after either the isolated or combined action of alkaline (sodium hydroxide) and oxidative (sodium hypochlorite) treatments. The highest values for the sum of carbonyl and carboxyl and enzymatic hydrolysis occurred in starches submitted to oxidative treatment at high active chlorine concentrations. The alkali treatment in isolation modified the pasting properties, reduced the paste temperature and increased the peak viscosity, breakdown, final viscosity and setback of starches. Starch modified by the action of sodium hypochlorite and hydroxide in combination presented more severe damage on granule surfaces. The results show that corn starch modified by the combined action of oxidative and alkaline treatments should be studied more, especially at the concentration limit of sodium hydroxide where gelatinization occurs. Under these conditions the effect of oxidation can be more intense and thus allow the production of starches with different properties and an increase in their industrial applications. © 2013 Society of Chemical Industry.

Combination of PDT and topical angiogenic inhibitor for treatment of port wine stain (PWS) birthmarks: a novel approach

NASA Astrophysics Data System (ADS)

Yuan, Kaihua; Huang, Qiaobing; Huang, Zheng

2009-06-01

Port wine stain (PWS) birthmarks are a congenital cutaneous vascular malformation involving ecstatic post-capillary venules. Current standard treatment for PWS is the pulsed dye laser (PDL). Vascular-targeted photodynamic therapy (PDT) has been used for the treatment of PWS in China since the early 1990's. Both can achieve a certain degree of color blanching in various types of PWS lesions. However, the majority of PWS lesions require multiple treatments. Some PWS lesions can recur or become darker after successful treatment. Recently, it has been proposed that this phenomenon might be initiated by neoangiogenesis that can be caused by treatment via wound healing response. The combined use of photothermolysis and a topical application of an angiogenic inhibitor such as Imiquimod and Rapamycin, were evaluated in several pilot studies. It is well-known that PDT can induce various host immune responses VEGF overexpression. Recent clinical data also show that improved clinical outcomes are obtained through the combination of ocular PDT and anti-VEGF therapy. This article will discuss rationales and implications of using such a combination modality and highlight recent progress based on our clinical experience and published data.

A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

PubMed

Dhir, Mashaal; Melin, Alyson A; Douaiher, Jeffrey; Lin, Chi; Zhen, Weining Ken; Hussain, Shahid M; Geschwind, Jean-Francois H; Doyle, Maria B Majella; Abou-Alfa, Ghassan K; Are, Chandrakanth

2016-06-01

To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

Combination of ozone and packaging treatments maintained the quality and improved the shelf life of tomato fruit

NASA Astrophysics Data System (ADS)

Zainuri; Jayaputra; Sauqi, A.; Sjah, T.; Desiana, R. Y.

2018-01-01

Tomato is very important vegetable crop but has short shelf life. The objective of this research was to determine the effect of ozone and packaging combination treatment on the quality and the storage life of tomato fruit. There were six treatments including: control (without ozone and packaging); without ozone and packaged with polyethylene bag; without ozone and polyethylene terephtalate punnet; with ozone but without packaging; with ozone and packaged with polyethylene bag; and with ozone and polyethylene terephtalate punnet. Each treatment was made into 3 replications. Tomato samples were harvested at turning stage. Ozone treatment was applied for 60 seconds. Tomatoes were then treated with and without packaging. The fruit were then stored at room temperature for up to 12 days. The parameters for assessment were water content, color, texture, weight loss and the population of naturally contamination Escherichia coli. Each parameter was assessed on day 0, 6 and 12 of storage. The results indicated that combination of ozone and packaging treatments significantly affected the physical and biochemical changes (water content, color, texture and weight loss) of the fruit, suppressed the microbiological contamination on the fruit and maintained fruit freshness or quality after 12 days of storage. The combination of ozone and perforated polyethylene packaging treatment was the best treatment to maintain the quality and prolonged the shelf life of tomato fruit to be 12 days at room temperature.

Combination use of atomoxetine hydrochloride and olanzapine in the treatment of attention-deficit/hyperactivity disorder with comorbid disruptive behavior disorder in children and adolescents 10-18 years of age.

PubMed

Holzer, Barry; Lopes, Vasco; Lehman, Robert

2013-08-01

The aim of this study was to assess the use of atomoxetine and olanzapine in combination to treat attention-deficit/hyperactivity disorder (ADHD) and comorbid disruptive behaviors in children and adolescents 10-18 years of age. Eleven subjects ages 10-18 received open-label atomoxetine and olanzapine for a 10 week treatment period. Patients were assessed at baseline, 2 weeks, 4 weeks, 6 weeks, and 10 weeks (posttreatment). ADHD improvement was measured through the ADHD Rating Scale (ADHD-RS) (Investigator and Parent ratings). Aggression was measured through the Modified Overt Aggression Scale (MOAS). The combined use of atomoxetine and olanzapine resulted in statistically significant improvement in ADHD symptoms and overt aggression from baseline to posttreatment. As evidenced by a 33% reduction in symptoms on the ADHD-RS-I and the MOAS, 73% of patients were considered responders to ADHD treatment, whereas 55% responded to treatment for aggression. Both medications were generally well tolerated. Olanzapine treatment was associated with significant weight gain. Patients gained, on average, 3.9 kg. throughout the treatment period. These data provide initial evidence that combination use of atomoxetine and olanzapine for the treatment of ADHD and comorbid disruptive behaviors was effective in reducing ADHD symptoms and aggressive behavior in a 10 week treatment period.

Granular activated carbon for simultaneous adsorption and biodegradation of toxic oil sands process-affected water organic compounds.

PubMed

Islam, Md Shahinoor; Zhang, Yanyan; McPhedran, Kerry N; Liu, Yang; Gamal El-Din, Mohamed

2015-04-01

Naphthenic acids (NAs) released into oil sands process-affected water (OSPW) during bitumen processing in Northern Alberta are problematic for oil sands industries due to their toxicity in the environment and resistance to degradation during conventional wastewater treatment processes. Granular activated carbon (GAC) has shown to be an effective media in removing biopersistent organics from wastewater using a combination of adsorption and biodegradation removal mechanisms. A simultaneous GAC (0.4 g GAC/L) adsorption and biodegradation (combined treatment) study was used for the treatment of raw and ozonated OSPW. After 28 days of batch treatment, classical and oxidized NAs removals for raw OSPW were 93.3% and 73.7%, and for ozonated OSPW were 96.2% and 77.1%, respectively. Synergetic effects of the combined treatment process were observed in removals of COD, the acid extractable fraction, and oxidized NAs, which indicated enhanced biodegradation and bioregeneration in GAC biofilms. A bacteria copy number >10(8) copies/g GAC on GAC surfaces was found using quantitative real time polymerase chain reaction after treatment for both raw and ozonated OSPW. A Microtox(®) acute toxicity test (Vibrio fischeri) showed effective toxicity removal (>95.3%) for the combined treatments. Therefore, the simultaneous GAC adsorption and biodegradation treatment process is a promising technology for the elimination of toxic OSPW NAs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of tDCS in Aphasia Rehabilitation: A Systematic Review of the Behavioral Interventions Implemented With Noninvasive Brain Stimulation for Language Recovery.

PubMed

Galletta, Elizabeth E; Conner, Peggy; Vogel-Eyny, Amy; Marangolo, Paola

2016-12-01

The purpose of this article is to review the behavioral treatments used in aphasia rehabilitation research that have been combined with transcranial direct current stimulation (tDCS). Although tDCS in aphasia treatment has shown promise, the results have not been conclusive, and their interpretation is further compounded by the heterogeneity of study characteristics. Because implementing a behavioral task during brain stimulation has been shown to be pivotal to the adjuvant effects of tDCS, we analyze the behavioral treatments that have been paired with tDCS. A computerized database search (PubMed) was completed to document and review aphasia treatment studies that combine behavioral treatment with noninvasive brain stimulation in the form of tDCS. Two authors reviewed each aphasia tDCS article published between 2008 and 2015 and evaluated (a) the behavioral interventions for aphasia that have been combined with tDCS, and (b) the methodological variables that may have influenced language outcomes in the tDCS aphasia literature. A review of the behavioral treatments implemented in tDCS aphasia rehabilitation studies highlights several methodological considerations for future investigations. Impairment-focused and pragmatic treatments have been implemented in tDCS aphasia research studies. No one behavioral approach stands out as the best treatment to combine with tDCS for the promotion of language recovery.